Author: "Service d'hématologie pédiatrique" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Service d'hématologie pédiatrique"' showing total 305 results

Start Over Author "Service d'hématologie pédiatrique"

305 results on '"Service d'hématologie pédiatrique"'

1. Risk factors for a severe form of COVID‐19 after allogeneic haematopoietic stem cell transplantation: a Société Francophone de Greffe de Moelle et de Thérapie cellulaire (SFGM‐TC) multicentre cohort study

Author: Stephanie Nguyen-Quoc, Hélène Salvator, Catherine Paillard, Michael Loschi, Jacques-Olivier Bay, Marie Robin, Yves Beguin, Marie-Thérèse Rubio, Ana Berceanu, Marie-Laure Chabi, Constance Xhaard, Aliénor Xhaard, Patrice Ceballos, Bénédicte Bruno, Maud D'Aveni, Jean-Hugues Dalle, Xavier Poiré, Tereza Coman, Karin Bilger, Yves Chalandon, Service d'Hématologie-Greffe, Hôpital Saint-Louis, Université Paris Diderot, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Service d'Hématologie, Institut Gustave Roussy, Université de Liège, Hôpitaux Universitaires de Genève (HUG), Service d'Hématologie, Bruxelles, Service d'Hématologie, CHU Nice, Service d'Hématologie Pédiatrique, CHRU Strasbourg, Service d'Hématologie Pédiatrique, CHU Lille, Service d'Hématologie, CHU Montpellier, Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, CHRU Strasbourg, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre du cancer, and UCL - (SLuc) Service d'hématologie
Subjects: Transplantation Conditioning, COVID-19 / diagnostic imaging, MESH: Allografts, Kaplan-Meier Estimate, Thrombocytopenia / etiology, Cohort Studies, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, MESH: Child, MESH: COVID-19, Transplantation Conditioning / adverse effects, Child, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, MESH: Transplantation Conditioning, COVID-19 / complications, MESH: Aged, ddc:616, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, 3. Good health, Haematopoiesis, COVID-19 / mortality, MESH: Young Adult, 030220 oncology & carcinogenesis, Child, Preschool, MESH: Immunosuppressive Agents, France, Stem cell, Immunosuppressive Agents, Cohort study, Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunosuppressive Agents / adverse effects, 03 medical and health sciences, Young Adult, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, France / epidemiology, Correspondence, medicine, Humans, MESH: SARS-CoV-2, MESH: Hematopoietic Stem Cell Transplantation, MESH: Kaplan-Meier Estimate, MESH: Thrombocytopenia, Aged, Retrospective Studies, MESH: Adolescent, Gynecology, MESH: Humans, business.industry, SARS-CoV-2, MESH: Child, Preschool, Hematopoietic Stem Cell Transplantation / adverse effects, COVID-19, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, Thrombocytopenia, MESH: France, Transplantation, business, 030215 immunology
Abstract: International audience
Published: 2021
Full Text: View/download PDF

2. Long-term management of leukocyte adhesion deficiency type III without hematopoietic stem cell transplantation

Author: Saultier, Paul, Szepetowski, Sarah, Canault, Matthias, Falaise, Celine, Poggi, Marjorie, Suchon, Pierre, Barlogis, Vincent, Michel, Gerard, Loyau, Stephane, Jandrot-Perrus, Martine, Bordet, Jean-Claude, Alessi, Marie-Christine, Chambost, Herve, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie pédiatrique [AP-HM Hôpital de la Timone], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, Inflammation et sepsis (EA 4609), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Service d'hématologie pédiatrique, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Assistance Publique - Hôpitaux de Marseille (APHM)-Université de la Méditerranée - Aix-Marseille 2- Hôpital de la Timone [CHU - APHM] (TIMONE), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Fondation pour la Recherche Medicale FDM20150633607, Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Prémilleux, Annick, and Hémostase, Inflammation et sepsis
Subjects: [SDV] Life Sciences [q-bio], integrine, [SDV]Life Sciences [q-bio], marqueur de leucocyte, transplantation cellulaire, Hematology, cellule hematopoietique, autosome, Online Only Articles, Hématologie
Published: 2018
Full Text: View/download PDF

3. Incidence and risk factors for clinical neurodegenerative Langerhans cell histiocytosis: a longitudinal cohort study

Author: Nathalie Aladjidi, Jean-François Emile, Frédéric Millot, Kamila Kebaili, Laurence Brugières, Valérie Taly, Anne Lutun, Catherine Paillard, Mohamed-Aziz Barkaoui, Julien Haroche, Zofia Hélias-Rodzewicz, Claire Galambrun, Fleur Cohen-Aubart, Hélène Pacquement, Jean Miron, Guy Leverger, Eric Jeziorski, Françoise Mazingue, Anne Pagnier, Marion Gillibert-Yvert, Anne Deville, Jean-Louis Stephan, Anne Lambilliotte, Nadine Martin-Duverneuil, Isabelle Pellier, Ahmed Idbaih, Geneviève Plat, Virginie Gandemer, Sébastien Héritier, Caroline Thomas, Jean Donadieu, Khê Hoang-Xuan, Despina Moshous, Ludovic Mansuy, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital mère et enfant, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut d’Hémato-Oncologie Pédiatrique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Toulouse [Toulouse], Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Institut Curie [Paris], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Universitaire de Nice (CHU Nice), Service Immuno Hémato-Onco Pédiatrique, CHU Grenoble, CHU Amiens-Picardie, CHU Trousseau [Tours], Service d'hématologie pédiatrique, CHU Saint-Etienne, Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Jean Bernard, Service de médecine de l'enfant et de l'adolescent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe labellisée Ligue contre le Cancer, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Molecular analysis of LCH samples was supported by a grant (#11413) from the Conquer Cancer Foundation ASCO Young Investigator Award, supported by the Strike 3 Foundation. This study received grants from the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent, Fédération Enfants et Santé, Association Recherche et Maladie Hématologiques de l’Enfant, Association Les 111 des Arts de Paris, Association la Petite Maison dans la Prairie. This project received constant support from the Association Histiocytose France. The French LCH registry was supported by a grant from InVS and INSERM for the rare disease registry, a grant from Roche and from the Gardrat Family. This study was based on research from the Centre de Reference des Histiocytoses (www.histiocytose.org)., Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], TALY, Valerie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], and CHU Pontchaillou [Rennes]
Subjects: Male, Pituitary gland, Pediatrics, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, BRAF, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Langerhans cell histiocytosis, Risk Factors, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cumulative incidence, Longitudinal Studies, Registries, Longitudinal cohort, Child, business.industry, Incidence (epidemiology), Incidence, neurodegeneration, Infant, Newborn, Infant, Neurodegenerative Diseases, Hematology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Histiocytosis, Langerhans-Cell, medicine.anatomical_structure, Bone lesion, 030220 oncology & carcinogenesis, Child, Preschool, Female, histiocytosis, business, Previously treated, 030215 immunology, Follow-Up Studies
Abstract: International audience; Neurodegenerative (ND) complications in Langerhans cell histiocytosis (LCH) are a late-onset but dramatic sequelae for which incidence and risk factors are not well defined. Based on a national prospective registry of paediatric LCH patients, we determined the incidence rate of clinical ND LCH (cND-LCH) and analysed risk factors, taking into account disease extent and molecular characteristics. Among 1897 LCH patients, 36 (1·9%) were diagnosed with a cND-LCH. The 10-year cumulative incidence of cND-LCH was 4·1%. cND-LCH typically affected patients previously treated for a multisystem, risk organ-negative LCH, represented in 69·4% of cND-LCH cases. Pituitary gland, skin and base skull/orbit bone lesions were more frequent (P < 0·001) in cND-LCH patients compared to those without cND-LCH (respectively 86·1% vs. 12·2%, 75·0% vs. 34·2%, and 63·9% vs. 28·4%). The 'cND susceptible patients' (n = 671) i.e., children who had experienced LCH disease with pituitary or skull base or orbit bone involvement, had a 10-year cND risk of 7·8% vs. 0% for patients who did not meet these criteria. Finally, BRAFV 600E status added important information among these cND susceptible patients, with the 10-year cND risk of 33·1% if a BRAFV 600E mutation was present compared to 2·9% if it was absent (P = 0·002).
Published: 2018
Full Text: View/download PDF

4. A landscape of germ line mutations in a cohort of inherited bone marrow failure patients

Author: Lucie Hernandez, Samuel Quentin, Elodie Lainey, Thierry Leblanc, Nicolas Boissel, Etienne Lengliné, Jean-Hugues Dalle, Julien Masliah-Planchon, Gérard Michel, Lionel Adès, Régis Peffault de Latour, Louis De Jaegere, Yves Bertrand, André Baruchel, Guy Leverger, Marie Sebert, Naddia Vasquez, Emmanuelle Clappier, Marc Muller, Olivier Bluteau, Stéphane Blanche, Isabelle Pellier, Gérard Socié, Wendy Cuccuini, Carine Domenech, Mathilde Hunault, Nicolas Blin, Raphael Itzykson, Sébastien Maury, Pierre Fenaux, Bénédicte Bruno, Mélanie Da Costa, Anna Raimbault, Jean Soulier, Claudine Schmitt, Arnaud Petit, Flore Sicre de Fontbrune, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Recherche clinique appliquée à l'hématologie (URP_3518), Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Service d'hématologie pédiatrique [Robert-Debré - APHP], Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Laboratoire d’Hématologie [CHU Henri-Mondor - APHP], CHU Henri Mondor, Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique [CHRU Nancy], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Henri Mondor [Créteil], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, MECOM, DNA Mutational Analysis, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, Cohort Studies, 03 medical and health sciences, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Fanconi anemia, Internal medicine, hemic and lymphatic diseases, Exome Sequencing, medicine, Humans, Child, Bone Marrow Diseases, Germ-Line Mutation, Exome sequencing, Chromosome 7 (human), business.industry, Infant, Newborn, Bone marrow failure, High-Throughput Nucleotide Sequencing, Infant, Cell Biology, Hematology, medicine.disease, Pancytopenia, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Child, Preschool, Myelodysplastic Syndromes, Female, Bone marrow, business
Abstract: International audience; Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders (GATA2, RUNX1), telomeropathies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling.
Published: 2018
Full Text: View/download PDF

5. Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience

Author: Nathalie Aladjidi, Marilyne Poirée, Catherine Paillard, Ilhem Rahal, Claire Galambrun, Imane Agouti, Mauricette Michallet, Pauline Simon, Yves Bertrand, Dominique Steschenko, Ibrahim Yakoub-Agha, Pascal Auquier, Régis Peffault de Latour, Marie Pierre Castex, Isabelle Thuret, Nathalie Garnier, Catherine Badens, Caroline Thomas, Corinne Pondarré, Gérard Michel, Patrick Lutz, Anderson Loundou, Pierre-Simon Rohrlich, Jean Hugues Dalle, Christophe Piguet, Jean Louis Stephan, Despina Moshous, Pierre Frange, Claire Berger, Gérard Socié, Françoise Bernaudin, Anne Lambilliotte, Cécile Dumesnil, TAN, Yossan-Var, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hopital Saint-Louis [AP-HP] (AP-HP), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre de référence maladie rare Thalassémie, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Rouen, Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Allergologie et d'Immunologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hopital L'Archet-II, Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU de Nantes, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital de la Timone [CHU - APHM] (TIMONE), AORC APHM 2011 (Appel d’Offre de Recherche Clinique), Service d'Allergologie et d'Immunologie [CHRU Toulouse], CHRU Toulouse, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Delayed puberty, Pediatrics, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Thalassemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Young adult, business.industry, Retrospective cohort study, Hematology, medicine.disease, 3. Good health, Transplantation, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business, Busulfan, 030215 immunology, medicine.drug
Abstract: International audience; In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant from a matched sibling donor. After transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and 2% heart failure. Hypogonadism was present in 56% of females and 14% of males. Female patients who went on to normal puberty after transplant were significantly younger at transplantation than those who experienced delayed puberty (median age 2.5 vs. 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or older and 2 other patients became pregnant following oocyte donation. In addition to patient’s age and higher serum ferritin levels at transplantation, time elapsed since transplant was significantly associated with decreased height growth in multivariate analysis. Weight growth increased after transplantation particularly in females, 36% of adults being overweight at last evaluation. A comprehensive long-term monitoring, especially of endocrine late effects, is required after hematopoietic stem cell transplantation for thalassemia.
Published: 2018
Full Text: View/download PDF

6. Metabolic syndrome in long-term survivors of childhood acute leukemia ă treated without hematopoietic stem cell transplantation: an LEA study

Author: Yves Bertrand, Paul Saultier, André Baruchel, Gérard Michel, Virginie Gandemer, Camille Vercasson, Patrick Lutz, Justyna Kanold, Audrey Contet, Guy Leverger, Stéphane Ducassou, Jean-Hugues Dalle, Marie-Dominique Tabone, Hervé Chambost, Sandrine Thouvenin, Marilyne Poirée, Nicolas Sirvent, Dominique Plantaz, Pascal Auquier, Julie Berbis, Claire Oudin, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Transplantation Médullaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital d'enfants, Service Hématologie Infantile, Hôpital Pellegrin Tripode, CHU Clermont-Ferrand-CIC Inserm 501, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, medicine.medical_treatment, [SHS.PSY]Humanities and Social Sciences/Psychology, Hematopoietic stem cell transplantation, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, Cohort Studies, 0302 clinical medicine, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Prevalence, Survivors, Child, Abdominal obesity, Metabolic Syndrome, 2. Zero hunger, education.field_of_study, Acute leukemia, Leukemia, Remission Induction, Age Factors, Articles, Hematology, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Combined Modality Therapy, 3. Good health, quality, Child, Preschool, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, medicine.symptom, Cohort study, Adult, medicine.medical_specialty, Adolescent, Immunology, Population, Lower risk, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Risk factor, education, National Cholesterol Education Program, Radiotherapy, business.industry, Cell Biology, medicine.disease, Surgery, Endocrinology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Metabolic syndrome, business, Body mass index, Follow-Up Studies
Abstract: INTRODUCTION Acute leukemia (AL) accounts for one third of childhood cancers. Cardiovascular conditions are serious long-term complications of childhood AL. However, few studies have investigated the risk of metabolic syndrome (MetS), a known predictor of cardiovascular disease, in patients treated without hematopoietic stem cell transplantation (HSCT). We describe the overall and age-specific prevalence, and risk factors for MetS and its components in the L.E.A. French cohort of childhood AL survivors treated without HSCT. METHODS L.E.A. is a long-term follow-up program involving all childhood AL survivors treated in the French participating centers since 1980 (clinicaltrials.gov identifier: NCT 01756599). MetS was defined according to the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATPIII) criteria revised in 2005. RESULTS The study included 650 adult patients. The mean age at evaluation was 24.2 years and the mean follow-up after leukemia diagnosis was 16.0 years. Central nervous system (CNS) irradiation was performed in 18.0% of patients (n=117). The prevalence of MetS was 6.9% (95% CI 5.1-9.2). The age-specific cumulative prevalence at 20, 25, 30 and 35 years of age was 1.3%, 6.1%, 10.8% and 22.4%, respectively, as shown in the Figure. The prevalence of decreased HDL-cholesterol, increased triglycerides, increased fasting glucose, increased blood pressure and increased abdominal circumference was 26.8%, 11.7%, 5.8%, 36.7% and 16.7%, respectively. The risk factors significantly associated with metabolic syndrome in the multivariate analysis were male gender, older age at last evaluation and higher body mass index at diagnosis, as shown in the Table. Cumulative steroid dose was not a significant risk factor. CNS-irradiated and non-irradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in non-irradiated patients. DISCUSSION Our study aimed to precisely describe the overall and age-specific prevalence, and risk factors of MetS in a large cohort of childhood AL survivors treated without HSCT. Notably, the subgroup treated with chemotherapy alone is one of the largest ever published, which is of particular interest as current protocols include very limited CNS irradiation indications. The prevalence of MetS was approximately two-fold higher than that observed in the adult French general population under 40 years of age. Moreover, the prevalence of MetS was found to increase markedly with age. An increased BMI at diagnosis was a risk factor for MetS. Children with an elevated BMI at diagnosis may have a genetic predisposition to metabolic disturbances or a socio-familial environment that renders them more vulnerable to metabolic complications. CNS irradiation was not found to be a risk factor for MetS. In the literature however, brain irradiation has been frequently reported as a risk factor for MetS. This variation with our study can probably be explained in part by the observation that our irradiated patients displayed a lower risk of elevated blood pressure along with a greater risk of increased abdominal circumference. The irradiated patients may therefore have a different metabolic risk profile compared with the non-irradiated patients, thereby suggesting varying mechanisms of pathogenesis. The results of our study confirm the need for early and prolonged follow-up of adult survivors of childhood AL even when treated without HSCT and without CNS irradiation. This prerequisite could enable both early detection of metabolic abnormalities and implementation of appropriate therapeutic procedures to reduce the morbidity and mortality associated with cardiovascular complications in such patients. Table. Multivariate analysis of potential risk factors for the metabolic syndrome OR: odds ratio; CI: confidence interval; BMI: body mass index; CNS: central nervous system; † OR per each additional year of follow-up; ‡ OR per each additional z-score unit; *significant values (p < 0.05) Table. Multivariate analysis of potential risk factors for the metabolic syndrome. / OR: odds ratio; CI: confidence interval; BMI: body mass index; CNS: central nervous system; † OR per each additional year of follow-up; ‡ OR per each additional z-score unit; *significant values (p < 0.05) Figure. Age-specific cumulative prevalence of the metabolic syndrome Figure. Age-specific cumulative prevalence of the metabolic syndrome Disclosures No relevant conflicts of interest to declare.
Published: 2016
Full Text: View/download PDF

7. The Impact of Donor Type on Long-Term Health Status and Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Leucemie de l'Enfant et de L'Adolescent Study

Author: André Baruchel, Gérard Michel, Guy Leverger, Geneviève Plat, Charlotte Jubert, Marie-Dominique Tabone, Hervé Chambost, Justyna Kanold, Catherine Paillard, Jean-Hugues Dalle, Claire Galambrun, Virginie Gandemer, Yves Bertrand, Jacinthe Bonneau, Maryline Poiree, Claire Freycon, Virginie Villes, Isabelle Pellier, Sandrine Visentin, Julie Berbis, Claire Oudin, Cécile Pochon, Anne Sirvent, Pascal Auquier, Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Groupe hospitalier Pellegrin, Service de Pédiatrie, Unité d'Oncologie et Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hématogoie pédiatrique, hôpital Sud, Service d'oncologie médicale [CHU Strasbourg], CHU Strasbourg, Service d'hématologie pédiatrique, CHU Clermont-Ferrand-CIC Inserm 501, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Toulouse [Toulouse], Hôpital Robert Debré Paris, Hôpital Robert Debré, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), the French National Clinical Research Program (grant no. PHRC10-24-02), French National Cancer Institute (InCA), French National Research Agency (ANR) [2011-043], Canceropole PACA [2016-03], Regional Council PACA [2016-03], Herault and the Bouches-du-Rhone departmental comities of the Ligue Contre le Cancer, French Institute for Public Health Research (IRESP), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Jonchère, Laurent
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Pediatrics, Cord blood transplantation, MESH: Late effects, medicine.medical_treatment, Health Status, MESH: Quality of life, Hematopoietic stem cell transplantation, Childhood leukemia, 0302 clinical medicine, Quality of life, Child, MESH: Cord blood transplantation, Acute leukemia, Late effect, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Tissue Donors, 3. Good health, Leukemia, 030220 oncology & carcinogenesis, Child, Preschool, Female, Cord Blood Stem Cell Transplantation, medicine.symptom, Unrelated Donors, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Hematopoietic stem cell transplantation, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Childhood leukemia, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Transplantation, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Late effects, Infant, Odds ratio, medicine.disease, Surgery, business, 030215 immunology
Abstract: International audience; We compared the long-term impact of donor type (sibling donor [SD] versus matched unrelated donor [MUD] or umbilical cord blood [UCB]) on late side effects and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic stem cell transplantation. We included 314 patients who underwent transplantation from 1997 to 2012 and were enrolled in the multicenter French Leucemie de l'Enfant et de L'Adolescent ("Leukemia in Children and Adolescents") cohort. More than one-third of the patients were adults at last visit; mean follow-up duration was 6.2 years. At least 1 late effect was observed in 284 of 314 patients (90.4%). The average number of adverse late effects was 2.1 +/- 1, 2.4 +/- 2, and 2.4 +/- 2 after SD, MUD, and UCB transplantation, respectively. In a multivariate analysis, considering the SD group as the reference, we did not detect an impact of donor type for most sequelae, with the exception of increased risk of major growth failure after MUD transplantation (odds ratio [OR], 2.42) and elevated risk of osteonecrosis after UCB transplantation (OR, 4.15). The adults and children's parents reported comparable QoL among the 3 groups. Adult patient QoL scores were lower than age- and sex-matched French reference scores for almost all dimensions. We conclude that although these patients are heavily burdened by long-term complications, donor type had a very limited impact on their long-term health status and QoL.
Published: 2016
Full Text: View/download PDF

8. Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age

Author: Abdellatif Tazi, Jean-François Emile, Yves Reguerre, Jean Donadieu, Khê Hoang-Xuan, Charlotte Rigaud, Yves Bertrand, Jean Miron, Caroline Thomas, Patrick Lutz, Mohamed Barkaoui, Claire Galambrun, Despina Moshous, Aurore Coulomb, Nathalie Aladjidi, Ludovic Mansuy, Virginie Gandemer, Corinne Armari-Alla, Anne Lambilliotte, Anne Deville, Geneviève Plat, Sébastien Héritier, Eric Jeziorski, Sylvie Fraitag, Nicolas Leboulanger, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, CIC - Bordeaux, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Tronche, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], OncoNeuroTek [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Service de pneumologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Groupe hospitalier Ambroise Paré, Registre français des neutropénies chroniques sévères, Institut National de la Santé et de la Recherche Médicale, Association Histiocytose France, Association la Petite Maison dans la Prairie, PHRC 2001 CHU Nantes, French Ministry of Health, RMHE, GARDRAT family, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service d'anatomie pathologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Service de neurologie Mazarin, CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Hospices Civils de Lyon ( HCL ) -CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] ( IHOPe ), Hospices Civils de Lyon ( HCL ) -Hôpital Femme-Mère-Enfant (HFME), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), CHU Félix Guyon, Service d'anatomie pathologique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Hôpital de la Salpétrière, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Refractory, Langerhans cell histiocytosis, Internal medicine, medicine, Humans, Cladribine, Child, [ SDV ] Life Sciences [q-bio], business.industry, historical comparisons, Age Factors, Infant, Newborn, Infant, Standard of Care, Hematology, medicine.disease, Combined Modality Therapy, Survival Analysis, Confidence interval, 3. Good health, Vinblastine, Surgery, Histiocytosis, Langerhans-Cell, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Population Surveillance, Cohort, Cytarabine, Female, France, business, Cohort study, medicine.drug, Follow-Up Studies
Abstract: International audience; The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five-year survival was 96·6% (95% confidence interval: 95·4–97·5%) overall, improving from 92% pre-1998 to 99% post-1998 (P \textless 0·001 adjusted to disease extent). This change was supported by an increase in 5-year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single-system patients, extended therapy duration, and more efficient second-line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent
Published: 2016
Full Text: View/download PDF

9. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)

Author: Pierre Bordigoni, Danielle Canioni, Michèle Milili, Nathalie Lambert, Claire Galambrun, Marie Ouachée-Chardin, Filomeen Haerynck, Françoise Le Deist, Despina Moshous, Christelle Lenoir, Stephanie Rigaud, Lionel Galicier, Fabien Touzot, Capucine Picard, Mohamed Hamidou, Hirokazu Kanegane, Ester Mejstrikova, Helen Chapel, Eduardo López-Granados, Stéphane Blanche, Alain Dabadie, Jana Pachlopnik Schmid, Pierre-Simon Rohrlich, Fabian Hauck, Geneviève de Saint Basile, Claudin Schiff, Jean-Louis Stephan, Alain Fischer, Isabelle Pellier, Nizar Mahlaoui, Sylvain Latour, Alain Fourmaintraux, Vincent Barlogis, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Graduate School of Medicine, University of Toyama, Department of pediatrics, University of Oxford [Oxford], Teaching Hospital Motol and 2nd Medical School, Charles University, Department of Pediatric Hematology and Oncology, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'immuno-hématologie pédiatrique [CHU Necker], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe Hospitalier Sud Réunion (GHSR), Centre Hospitalier Universitaire [Rennes], Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Department of Paediatric Pulmonology, Ghent University Hospital, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Département de pédiatrie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, CHU Saint-Etienne, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'étude des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), University of Oxford, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Collège de France - Chaire Médecine expérimentale (A. Fischer), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Groupe Hospitalier Sud Réunion ( GHSR ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Assistance publique - Hôpitaux de Paris (AP-HP)
Subjects: Male, MESH : Retrospective Studies, MESH: X-Linked Inhibitor of Apoptosis Protein, MESH : Aged, MESH : Child, Preschool, Biochemistry, Cohort Studies, Immunoenzyme Techniques, Hypogammaglobulinemia, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, MESH : Child, MESH: Child, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, XIAP Deficiency, Signaling Lymphocytic Activation Molecule Associated Protein, X-Linked Lymphoproliferative Syndrome, Child, MESH: Cohort Studies, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Lymphoproliferative Disorders, Intracellular Signaling Peptides and Proteins, MESH : Infant, Hematology, MESH : Adult, Middle Aged, MESH : Survival Rate, MESH: Infant, 3. Good health, Survival Rate, MESH : Phenotype, Phenotype, MESH: Young Adult, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, Adult, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH: Survival Rate, MESH : Male, Immunology, MESH : Young Adult, MESH : Cohort Studies, X-Linked Inhibitor of Apoptosis Protein, Biology, MESH: Phenotype, Virus, Young Adult, 03 medical and health sciences, MESH : Intracellular Signaling Peptides and Proteins, MESH : Immunoenzyme Techniques, MESH : Adolescent, MESH: Intracellular Signaling Peptides and Proteins, medicine, Humans, MESH : Middle Aged, MESH: Immunoenzyme Techniques, Aged, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, Hemophagocytic lymphohistiocytosis, Cytopenia, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, X-linked lymphoproliferative disease, MESH: Adult, MESH: Retrospective Studies, Cell Biology, medicine.disease, Lymphoproliferative Disorders, MESH: Male, MESH : X-Linked Inhibitor of Apoptosis Protein, Mutation, Histopathology, MESH: Female, 030215 immunology
Abstract: X-linked lymphoproliferative syndromes (XLP) are primary immunodeficiencies characterized by a particular vulnerability toward Epstein-Barr virus infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP type 1 (XLP-1) is caused by mutations in the gene SH2D1A (also named SAP), whereas mutations in the gene XIAP underlie XLP type 2 (XLP-2). Here, a comparison of the clinical phenotypes associated with XLP-1 and XLP-2 was performed in cohorts of 33 and 30 patients, respectively. HLH (XLP-1, 55%; XLP-2, 76%) and hypogammaglobulinemia (XLP-1, 67%; XLP-2, 33%) occurred in both groups. Epstein-Barr virus infection in XLP-1 and XLP-2 was the common trigger of HLH (XLP-1, 92%; XLP-2, 83%). Survival rates and mean ages at the first HLH episode did not differ for both groups, but HLH was more severe with lethal outcome in XLP-1 (XLP-1, 61%; XLP-2, 23%). Although only XLP-1 patients developed lymphomas (30%), XLP-2 patients (17%) had chronic hemorrhagic colitis as documented by histopathology. Recurrent splenomegaly often associated with cytopenia and fever was preferentially observed in XLP-2 (XLP-1, 7%; XLP-2, 87%) and probably represents minimal forms of HLH as documented by histopathology. This first phenotypic comparison of XLP subtypes should help to improve the diagnosis and the care of patients with XLP conditions.
Published: 2011
Full Text: View/download PDF

10. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome

Author: Mohamad Mohty, Fanny Rialland, Patrick Lutz, Karine Baumstarck, Anderson Loundou, Sophie Esmiol, Charlotte Jubert, Claire Galambrun, Ibrahim Yakoub-Agha, Mauricette Michallet, Didier Blaise, Cécile Pochon, Anne Sirvent, Jean-Hugues Dalle, Gérard Michel, Claire Oudin, Bénédicte Bruno, Virginie Gandemer, Aude Marie-Cardine, Vanderson Rocha, Mylène Seux, Noel Milpied, Cecile Renard, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Gustave Roussy (IGR), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chimie Provence (LCP), Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), France Monacord, Centre Scientifique de Monaco (CSM), Hôpital Robert Debré Paris, Hôpital Robert Debré, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)
Subjects: Male, Transplantation Conditioning, [SHS.PSY]Humanities and Social Sciences/Psychology, Graft vs Host Disease, Biochemistry, Gastroenterology, 0302 clinical medicine, Child, Acute leukemia, Leukemia, Hematology, Total body irradiation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Child, Preschool, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Whole-Body Irradiation, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Survival rate, Antilymphocyte Serum, business.industry, Myelodysplastic syndromes, Cell Biology, medicine.disease, Surgery, Transplantation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Myelodysplastic Syndromes, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Busulfan, 030215 immunology
Abstract: Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has a been proposed to increase the cell dose. We report a prospective a randomized study, designed to compare single-vs double-UCB a transplantation in children and young adults with acute leukemia in a remission or myelodysplasia. Eligible patients had at least two 4-6 a HLA-identical UCBs with >3x10(7) nucleated cells/kg for the first and a >1.5x10(7) for the second. The primary end point was the 2-year a cumulative incidence of transplantation strategy failure, a composite a end point including transplant-related mortality (TRM), engraftment a failure, and autologous recovery. Randomized patients who did not a proceed to transplantation due to refractory disease were considered a transplantation failures. A total of 151 patients were randomized and a included in the intent-to-treat analysis; 137 were transplanted. a Double-UCB transplantation did not decrease transplantation strategy a failure (23.4% 6 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant a survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% a +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation a compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% a after double-unit transplantation. The final relapse risk did not a significantly differ, but relapses were delayed after double-unit a transplantation. Overall incidences of graft-versus-host disease (GVHD) a were similar, but chronic GVHD was more frequently extensive after a double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, a P=.02). In an exploratory subgroup analysis, we found a significantly a lower relapse risk after double-unit transplantation in patients a receiving total body irradiation without antithymocyte globulin (ATG), a whereas the relapse risk was similar in the group treated with busulfan, a cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell a dose remains the standard of care and leads to low TRM. Double-unit a transplantation should be reserved for patients who lack such units. a This trial was registered at www. clinicaltrials. gov as #NCT01067300.
Published: 2016
Full Text: View/download PDF

11. Pharmacokinetic and Pharmacodynamic Characterization of Graspa Versus Native L-Asparaginase in Combination with Cooprall Chemotherapy in a Phase 3 Randomized Trial for the Treatment of Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01 51851 7)

Author: Thomas, Xavier, Bertrand, Yves, Baruchel, Andre, Blin, Nicolas, Tavernier, Emmanuelle, Ducassou, Stephane, Norbert Vey, Gandemer, Virginie, Cacheux, Victoria, Mazingue, Francoise, Raffoux, Emmanuel, Plat, Genevieve, Fernandes, Jose, Poiree, Maryline, Fornecker, Luc, Stephan, Jean-Louis, Hunault, Mathilde, Auvrignon, Anne, Leguay, Thibault, Lepretre, Stephane, Ferster, Alina, Pellier, Isabelle, Plouvier, Emmanuel, Schmitt, Claudine, Bonin, Cecile, Godfrin, Yann, El Hariry, Iman, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Hôpital Pellegrin Tripode, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Pediatric Onco-Hematology Unit, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Clermont-Ferrand, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie, Unité d'Oncologie et Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie pédiatrique, CHU Saint-Etienne, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV]Life Sciences [q-bio]
Abstract: WOS:000368020102004; International audience; Conference: 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL - DEC 05-08, 2015
Published: 2015

12. Updated Clinical Activity of Graspa Versus Native l-Asparaginase in Combination with Cooprall Regimen in Phase 3 Randomized Trial in Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)

Author: José Fernandes, Thibault Leguay, Norbert Vey, Stéphane Ducassou, Stéphane Leprêtre, Jean-Louis Stephan, Emmanuelle Tavernier, Iman El Hariry, Emmanuel Plouvier, Geneviève Plat, Poiree Maryline, Dominique Plantaz, Cecile Bonin, Anne Auvrignon, Xavier Thomas, Yves Bertrand, Claudine Schmitt, Françoise Mazingue, Alina Ferster, Luc Fornecker, Mathilde Hunault, Victoria Cacheux, Nicolas Blin, Emmanuel Raffoux, André Baruchel, Isabelle Pellier, Virginie Gandemer, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Pellegrin Tripode, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Pediatric Onco-Hematology Unit, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Clermont-Ferrand, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie pédiatrique, CHU Saint-Etienne, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Hématologie Infantile, CHU Grenoble, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Oncology, medicine.medical_specialty, Pediatrics, Asparaginase, [SDV]Life Sciences [q-bio], Immunology, 02 engineering and technology, Biochemistry, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Randomized controlled trial, law, Internal medicine, Acute lymphocytic leukemia, medicine, In patient, Adverse effect, 030304 developmental biology, 0303 health sciences, Surrogate endpoint, business.industry, Cell Biology, Hematology, 021001 nanoscience & nanotechnology, medicine.disease, Chemotherapy regimen, 3. Good health, Regimen, chemistry, 0210 nano-technology, business
Abstract: Background Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies, which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA (proposed eryaspase, E-Coli L-Asparaginase encapsulated into red blood cells) improves pharmacokinetics, tolerability and maintain circulating asparaginase (ASPA) activity due to the protective barrier of the erythrocyte membrane. In a recent Phase III trial, it has shown to prolong the asparaginase activity and significantly reduce the incidence of allergic reactions in pts with relapsed ALL. In the non-allergic pts, GRASPA significantly reduced the incidence of hypersensitivity (0% vs 46%; p100 IU/l was 21 ± 5 vs 9 ± 7 days in GRASPA and L-ASP, respectively (p Methods This open, randomized international Phase 3 study enrolled pts with relapsed ALL. The co-primary endpoints were the duration of ASPA activity > 100IU/L and the incidence of hypersensitivity during induction. Key secondary endpoints were complete remission, minimal residual disease, relapse rate, event free survival (EFS) and overall survival (OS). Pts (n=80), aged 1-55 years without prior hypersensitivity were randomized to GRASPA (150 IU/kg, n=26, Arm A) or native L-asparaginase (L-ASP, 10,000 IU/m², n= 28, Arm B). Additionally, 26 pts with prior hypersensitivity were treated with GRASPA in a single stratum (Arm C). All pts received COOPRALL protocol as a backbone chemotherapy. Results A total of 80 pts with relapsed and or refractory ALL were enrolled into the trial. There were a greater proportion of pts who completed the induction treatment in GRASPA arm (65%) than in the L-ASP arm (46%). The main reasons for treatment discontinuation were: target levels of asparagine depletion not reached (64%) in GRASPA arm, and adverse events (58%) in the L-ASP arm. In addition, in the L-ASP arm, 5 (19%) pts prematurely discontinued treatment due to disease progression. As of the cut-off date (28th August 2014), the majority of pts (63%) still continued in the study and followed-up for survival. The relapse rate at 6 and 12 mo was low, and accounted for 3 (13%; 95% CI: 2.6; 32.4) and 5 (26%; 95% CI: 9.1; 51.2) in the GRASPA arm, compared to 1 pt (5%) and 3 (17%; 95% CI: 3.6; 41.4) in the L-ASP arm, respectively. Except for L-ASP, and adult patients, the median EFS and OS were not reached for GRASPA in the entire set or in children, either at 12 months. Overall, there was a trend across all groups with lower EFS and OS event rates with GRASPA compared to L-ASP, as presented in table below. The 2-year follow up will be additionally provided at the meeting Table 1. GRASPA vs L-ASP All patients GRASPA = 26 L-ASP = 28 Children GRASPA = 21 L-ASP = 21 Adults GRASPA = 5 L-ASP = 7 12 mo EFS Median (mo) NR vs 11.6 NR 4.6 vs 1.6 Events 30.8% vs 50.0% 19.1% vs 38.1% 80% vs 85.7% HR 0.54 0.47 0.69 95% CI 0.23; 1.26 0.15; 1.47 0.20; 2.44 P Value* 0.153 0.196 0.569 12 mo OS Median (mo) NR NR 10 vs 8.2 Events 23.1% vs 32.1% 4.8% vs 14.3% 20% vs 42.8% HR 0.63 0.34 0.39 95% CI 023; 1.74 0.05; 2.42 0.05; 2.81 P Value* 0.377 0.424 0.705 *P value in all subsets is not statistically significant Conclusion GRASPA has demonstrated both safety and activity in pts with relapsed ALL, and provides an alternative treatment option for those patients. Disclosures Bertrand: ERYTECH Pharma: Consultancy. Thomas:ERYTECH Pharma: Consultancy. Vey:Roche: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Bonin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.
Published: 2015

13. Evaluation of the Impact of the Presence of Neutralizing L-Asparaginase Antibodies on the Efficacy and Safety of Graspa in Phase 3 Randomized Trial Versus Native L-Asparaginase in Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)

Author: Yves Bertrand, Françoise Mazingue, Cecile Bonin, Mathilde Hunault, Yann Godfrin, Anne Auvrignon, Claudine Schmitt, Jean-Louis Stephan, Dominique Plantaz, Emmanuel Raffoux, José Fernandes, Nicolas Blin, Geneviève Plat, Thibault Leguay, Maryline Poiree, Emmanuel Plouvier, Alina Ferster, Emmanuelle Tavernier, Xavier Thomas, André Baruchel, Stéphane Ducassou, Luc Fornecker, Victoria Cacheux, Stéphane Leprêtre, Iman El Hariry, Norbert Vey, Isabelle Pellier, Virginie Gandemer, Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Pellegrin Tripode, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pediatric Onco-Hematology Unit, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie, Unité d'Oncologie et Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie pédiatrique, CHU Saint-Etienne, CHU Pitié-Salpêtrière [AP-HP], CHU Trousseau [APHP], Service Hématologie Infantile, CHU Grenoble, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Oncology, Asparaginase, medicine.medical_specialty, Lymphoblastic Leukemia, [SDV]Life Sciences [q-bio], Immunology, 02 engineering and technology, 030226 pharmacology & pharmacy, Biochemistry, law.invention, L asparaginase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Acute lymphocytic leukemia, Internal medicine, medicine, In patient, biology, business.industry, Cell Biology, Hematology, 021001 nanoscience & nanotechnology, medicine.disease, Chemotherapy regimen, 3. Good health, chemistry, biology.protein, Antibody, 0210 nano-technology, business
Abstract: Background Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies, which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA (eryaspase - proposed INN) is an L-asparaginase encapsulated into the red blood cells. In a recent Phase III trial, it has shown to prolong the asparaginase activity and significantly reduce the incidence of allergic reactions in pts with relapsed ALL. Methods This open, randomized international Phase 3 study enrolled pts with relapsed ALL. The co-primary endpoints were the mean duration of asparaginase (ASPA) activity > 100 IU/L and incidence of hypersensitivity reactions during induction phase. Key secondary endpoints were safety, tolerability, complete remission and minimal residual disease rate, PK, and anti-ASPA antibodies (A-Abs) at baseline. Pts (n=80), aged 1-55 years without prior hypersensitivity were randomized to GRASPA (150 IU/kg, n=26, Arm A) or native L-asparaginase (L-ASP, 10,000 IU/m², n=28, Arm B). Additionally, 26 pts with prior hypersensitivity were treated with GRASPA in a single stratum (Arm C). All pts received COOPRALL protocol as a backbone chemotherapy. Here we report the impact of A-Abs on safety and efficacy of GRASPA. Assessments were performed at Day 4, 13, 18, and 27 (F1/F2 block), Day 6, 15, and 27 (VANDA block), and Day 6, 12 (R2/R1 block). Results At baseline, 23%, 25%, and 58% of pts had +ve A-Abs status in Arms A, B, and C, respectively. The mean duration of total ASPA activity (Days) adjusted for baseline antibody status is presented below, and shows that activity slightly differed with positive status; however, GRASPA maintained higher activity compared to L-ASP: Table 1. GRASPA L-ASP GRASPA L-ASP GRASPA (Arm C) Antibody status Negative Positive Negative Positive N 20 21 6 7 11 15 Mean (SD) 22.4 (3.6) 10.31 (8.1) 14.17 (5.1) 6.5 (4.0) 18.9 (6.8) 18.4 (6.2) Median 22.4 8.3 12.2 7.0 21.8 21.7 Min; Max 10.2; 30.7 0.0; 25.0 9.8; 21.8 1.9; 14.0 9.1; 27.9 6.9; 25.0 The incidence of hypersensitivity reactions were 0%, 7/21 (33%), and 2/11 (18%) in pts with negative A-Abs, compared to 0%, 6/7 (85.7%), and 1/15 (7%) in pts with positive A-Abs, in arms A, B and C, respectively. The CR rate during induction was 75%, 48%, and 64% in pts with negative A-Abs, compared to 33%, 14% and 48% in pts with positive A-Abs, in arms A, B and C, respectively. Conclusion These results show that about one third of pts without evidence of prior hypersensitivity have silent A-Abs activation. Positive A-Abs appeared to attenuate the clinical activity in all treatments arms. GRASPA consistently demonstrated activity and improved hypersensitivity regardless of A-Abs status, and therefore, GRASPA is a suitable option for patients with relapsed ALL. Disclosures Bertrand: ERYTECH Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Thomas:ERYTECH Pharma: Consultancy. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Bonin:ERYTECH Pharma: Employment. Godfrin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.
Published: 2015

14. Late cardiomyopathy in childhood acute myeloid leukemia survivors: a study from the LEA program

Author: Gérard Michel, Pascal Chastagner, Guy Leverger, Maya Allouche, Yves Bertrand, Marie-Dominique Tabone, Hervé Chambost, Vincent Barlogis, Camille Vercasson, Laure Saumet, André Baruchel, Sandrine Thouvenin-Doulet, Maryline Poiree, Dominique Plantaz, Pascal Auquier, Justyna Kanold, Julie Berbis, Claire Oudin, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service d'hématologie, CHU Lyon, Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Hématologie Infantile, CHU Grenoble, Service de Pédiatrie, Unité d'Oncologie et Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Clermont-Ferrand-CIC Inserm 501, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and HAL AMU, Administrateur
Subjects: CHILDREN, Kaplan-Meier Estimate, THERAPY, 0302 clinical medicine, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, ADOLESCENTS, Cumulative incidence, Survivors, Child, RISK, Acute leukemia, Incidence, Childhood Acute Myeloid Leukemia, Hematology, Leucemie Enfant & Adolescent program, CANCER, 3. Good health, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Child, Preschool, France, Cardiomyopathies, medicine.drug, medicine.medical_specialty, Anthracycline, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, late cardiomyopathy, ANTHRACYCLINE CARDIOTOXICITY, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Multicenter trial, Internal medicine, medicine, MANAGEMENT, Idarubicin, Humans, Online Only Articles, ACUTE LYMPHOBLASTIC-LEUKEMIA, Cardiotoxicity, business.industry, Infant, Newborn, pediatric acute myeloid leukemia, Infant, Surgery, Transplantation, business, 030215 immunology, Follow-Up Studies
Abstract: International audience; Late cardiomyopathy in childhood acute myeloid leukemia survivors: a study from the L.E.A. program Prognosis of pediatric acute myeloid leukemia (AML) has improved significantly over the past two decades with survival rates now approaching 70%. 1 Therapy consists of a limited number of intensive chemotherapy courses mainly based on cytarabine and anthracycline. 2,3 Many pediatric late anthracycline cardiotoxicity studies have concerned heterogeneous diagnostic groups. Moreover, single childhood cancer studies were mainly conducted in acute lym-phoblastic leukemia, whereas the highest doses of anthra-cycline are given in children with AML. 4-6 We report here a prospective multi-centric study of late cardiotoxicity in 185 patients surviving childhood AML. All were treated after 1989 in French clinical trials using intensive chemotherapy alone or chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). L.E.A. (Leucémie Enfant & Adolescent) is a French prospective long-term follow-up program involving all childhood acute leukemia survivors treated in the participating centers since 1980. Details of the programm are provided elsewhere. 7 As of 31 December 2011, 282 childhood AML survivors fulfilled the L.E.A. inclusion criteria and 218 (77.3%) of them agreed to participate. Among these 218, 185 were treated according to one of the 6 multicenter trial protocols ongoing in France after January 1989. All 185 had serial echocardiographic examination as part of their L.E.A. program, and all were included in the present study. All provided written informed consent. Cardiotoxicity was defined by either clinical symptoms of congestive heart failure or by an abnormal echocardiographic left ventricular function. Left ventricular function was considered abnormal when the shortening fraction (SF) was less than 28% or when the left ventricular ejection fraction (LVEF) was less than 55% on 2D echocardiography. 8-10 Cardiotoxicity was classified as late when it started or persisted beyond one year after the completion of first-line treatment. 9 Cumulative anthracycline doses used in each trial are described in the Online Supplementary Table S1, as well as the doxorubicin-equivalent doses using conversion factors of 0.83, 4.0 and 5.0 for daunorubicin, mitoxantrone and idarubicin, respectively. 10,11 Assessment of health status, long-term late effects on health-related quality of life (QoL), and statistical analysis are described in the Online Supplementary Appendix. Characteristics of the study cohort are summarized in Table 1. Median age at the time of AML diagnosis and median follow-up duration to last cardiac evaluation were 6.53 and 9.5 years, respectively. Thirty-seven patients had a history of relapse. Median cumulative anthracycline dose was 372 mg/m² (Online Supplementary Figure S1). Ninety-nine patients were treated by chemotherapy alone, whereas the other 86 patients also received HSCT (57 in first remission, 25 in second remission, and 4 in more advanced disease). Thirty children received total body irradiation (TBI), but only 10 among the 57 transplanted in first remission did so. Median number of echographic evaluations was 3 per patient. Subclinical cardiotoxicity (SCC) was observed in 23 of 185 patients (12.4%) at least once during their follow-up program. Median time from AML diagnosis to SCC detection was 4.40 years. In these 23 patients, the median value of the worst SF was 27% and the median value of the worst LVEF was 52. Only 3 of 23 patients had a worse SF value of less than 25% (2 had 20%; 1 had 24%). Six of 23 received anti-congestive therapy and none had cardiac transplantation. Five of those receiving anti-congestive therapy were still being treated at time of last evaluation, and 4 had more than 28% SF and more than 55% LVEF. Seventeen patients never received treatment: 11 had spontaneous improvement with more than 28% SF and more than 55% LVEF at last evaluation. Finally, at last cardiac evaluation, only 8 patients had an abnormal left ventricular function. Cumulative incidence (CI) of cardiotoxicity, estimated by the Kaplan-Meier method was 16% and 27% at 10 and 15 years, respectively (Figure 1A). CI of anti-conges-tive treatment at the same follow-up times was 5% and 7%. The risk of developing cardiotoxicity depended on a previous history of relapse and on the cumulative anthracy-cline dose. At ten years from diagnosis, CI was 35% versus 11% in patients with or without history of relapse (P=0.02) (Figure 1B). Among 148 patients without any history of relapse, 10-year CI of cardiotoxicity was 14% in 97 patients treated with chemotherapy alone versus 8% in 51 patients who underwent HSCT in first remission (NS, Figure 1C). In transplanted children, the risk was not modified by either a grade 2-4 acute or an extensive chronic graft-versus-host disease. The CI of anti-congestive treatment in these 148 patients who never experienced relapse was 3% at ten and
Published: 2015
Full Text: View/download PDF

15. Household exposure to pesticides and risk of childhood acute leukaemia

Author: Brigitte Nelken, Florence Menegaux, André Baruchel, Brigitte Lescoeur, Yves Bertrand, Denis Hémon, Danièle Sommelet, Guy Leverger, Jacqueline Clavel, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service pédiatrique d'hématologie, Hospices Civils de Lyon (HCL)-Hôpital Debrousse, Hospices Civils de Lyon (HCL), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service pédiatrique d'hématologie-oncologie, Hôpital Jeanne de Flandre [Lille], Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Kaniewski, Nadine
Subjects: Male, Insecticides, Pediculosis, Ethnic origin, 010501 environmental sciences, MESH: Epidemiologic Methods, 01 natural sciences, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, MESH: Child, Epidemiology, MESH: Maternal Exposure, Child, Acute leukemia, Leukemia, MESH: Infant, Newborn, Environmental exposure, Lice Infestations, MESH: Prena, MESH: Infant, 3. Good health, Maternal Exposure, Child, Preschool, Prenatal Exposure Delayed Effects, 030220 oncology & carcinogenesis, Acute Disease, Paternal Exposure, MESH: Acute Disease, Female, Original Article, medicine.medical_specialty, Adolescent, MESH: Environmental Exposure, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Environmental health, MESH: Leukemia, medicine, Humans, MESH: Pesticides, Pesticides, Risk factor, 0105 earth and related environmental sciences, MESH: Adolescent, MESH: Paternal Exposure, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, Newborn, MESH: Lice Infestations, Public Health, Environmental and Occupational Health, Infant, Environmental Exposure, Odds ratio, medicine.disease, MESH: Male, MESH: Insecticides, Surgery, Scalp Dermatoses, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Epidemiologic Methods, business, MESH: Female
Abstract: International audience; OBJECTIVES: To investigate the relation between childhood acute leukaemia and household exposure to pesticides. METHODS: The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics. RESULTS: Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3). CONCLUSION: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.
Published: 2006
Full Text: View/download PDF

16. Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukaemia

Author: Christoph Steffen, André Baruchel, Brigitte Lescoeur, Denis Hémon, Stéphanie Bellec, Brigitte Nelken, Jacqueline Clavel, N Philippe, Guy Leverger, Florence Menegaux, Danièle Sommelet, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service pédiatrique d'hématologie-oncologie, Hôpital Jeanne de Flandre [Lille], Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Kaniewski, Nadine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Cancer Research, Pediatrics, Maternal smoking, Ethnic origin, Coffee, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, Risk Factors, MESH: Risk Factors, MESH: Child, 030212 general & internal medicine, MESH: Maternal Exposure, Child, Acute leukemia, Leukemia, MESH: Case-Control Studies, MESH: Infant, MESH: Mothers, Alcohol consumption during pregnancy, 3. Good health, Oncology, Maternal Exposure, Child, Preschool, 030220 oncology & carcinogenesis, MESH: Tobacco Smoke Pollution, Female, MESH: Socioeconomic Factors, medicine.medical_specialty, Adolescent, Alcohol Drinking, Childhood leukemia, Mothers, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Leukemia, medicine, Humans, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Case-control study, Infant, MESH: Coffee, medicine.disease, MESH: Male, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Socioeconomic Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Tobacco Smoke Pollution, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, MESH: Alcohol Drinking
Abstract: International audience; INTRODUCTION: We investigated the role of maternal alcohol and coffee drinking and parental smoking on the risk of childhood acute leukemia in a multicenter case-control study. METHODS: The study included 280 incident cases and 288 hospitalized controls, frequency matched with the cases by age, gender and center. Data collection was completed by face-to-face standardized interviews of the case and control mothers. RESULTS: An association with maternal alcohol consumption during pregnancy was observed with acute lymphoid leukemia (ALL) (OR=2.0 [1.4-3.0]) and acute non-lymphoid leukemia (ANLL) (OR=2.6 [1.2-5.8]). Maternal coffee consumption during pregnancy was associated with childhood acute leukemia, ORs increasing in ALL with coffee consumption (OR=1.1 [0.7-1.8], OR=2.4 [1.3-4.7] and OR=3.1 [1.0-9.5], respectively, for < or =3, 4-8 and >8 cups/day). No association with maternal smoking during pregnancy or parental smoking before or after the index child's birth was observed. DISCUSSION: Our results suggest an association with maternal alcohol and coffee drinking during pregnancy and call for further investigations. Besides, the present study does not support the hypothesis of an increase in the risk of childhood leukemia related to parental smoking.
Published: 2005
Full Text: View/download PDF

17. A Phase I Study of Clofarabine With Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (VANDEVOL Study of the French SFCE Acute Leukemia Committee)

Author: Nelken, Brigitte, Cavé, Hélène, Leverger, Guy, Galambrun, Claire, Plat, Genevieve, Schmitt, Claudine, Thomas, Caroline, Vérité, Cecile, Brethon, Benoit, Gandemer, Virginie, Bertrand, Yves, Baruchel, André, Rohrlich, Pierre, Pôle Enfant, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord (France), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pellegrin Tripode, Pediatric Onco-Hematology Unit, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Direction de la Recherche Clinique du CHRU de Lille, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, and Jonchère, Laurent
Subjects: Male, Salvage Therapy, Adolescent, Dose-Response Relationship, Drug, Maximum Tolerated Dose, Adenine Nucleotides, [SDV]Life Sciences [q-bio], acute lymphoblastic leukemia, phase I, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Dexamethasone, [SDV] Life Sciences [q-bio], Young Adult, resistant disease, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Asparaginase, Humans, Female, Arabinonucleosides, Mitoxantrone, Neoplasm Recurrence, Local, Child, Clofarabine, Etoposide
Abstract: International audience; BACKGROUND: Current outcome of very early relapse of acute lymphoblastic leukemia (ALL) in children remains poor. As a single agent, clofarabine provided a response rate of 26% in childhood ALL second relapse and, in combination with cyclophosphamide and etoposide, a 44% complete remission and complete remission without platelet recovery (CR+CRp) rate. Further multi-drug combinations need to be investigated. We used the VANDA regimen as a template, cytarabine being replaced by clofarabine. PATIENTS AND METHODS: A phase I study combining escalating doses of clofarabine (25% increments from 20 to 40 mg/m(2) /d) with fixed doses of mitoxantrone, etoposide, asparaginase, and dexamethasone was undertaken in children presenting with very early or second or post-transplant ALL relapse. RESULTS: Twenty patients were enrolled, 19 were evaluable. Four patients had previously been allografted. Dose-limiting toxicity (DLT) appeared at dose level 3 (32 mg/m(2) ), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m(2) ), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m(2) . There was no toxic death. Eleven (57.9%) patients achieved a CR. Six patients proceeded to allogeneic stem cell transplantation. CONCLUSION: Clofarabine MTD was 32 mg/m(2) /d in this combination which appeared feasible and effective in this population. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc
Published: 2014
Full Text: View/download PDF

18. Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics, predictive factors and impact on post-transplant outcome

Author: Christophe Picard, Anderson Loundou, Claire Oudin, Hervé Chambost, Isabelle Thuret, Elodie Elkaim, Claire Galambrun, Catherine Curtillet, Gérard Michel, Vincent Barlogis, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, medicine.medical_specialty, Cord, Multivariate analysis, Transplantation Conditioning, Adolescent, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Disease, Gastroenterology, Minor Histocompatibility Antigens, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Prospective Studies, Child, Cord blood transplantation, Transplantation Chimera, business.industry, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Allografts, 3. Good health, Hematopoiesis, Haematopoiesis, Graft-versus-host disease, Treatment Outcome, surgical procedures, operative, Quartile, Child, Preschool, Immunology, Female, Cord Blood Stem Cell Transplantation, business
Abstract: International audience; This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99*9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0*1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61*8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0*03), older age (above 2*16 years, the first quartile of age, P = 0*0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P
Published: 2014
Full Text: View/download PDF

19. L’alliance thérapeutique est associée à l’adhésion au traitement chez les enfants atteints d’arthrite juvénile idiopathique

Author: Valérie Devauchelle-Pensec, Anaïs Arbault, Elisabeth Solau-Gervais, Irène Lemelle, L. Sparsa, Agnès Duquesne, Tu-Anh Tran, Anne Lohse, Camille Alleyrat, Francis Guillemin, Pascal Pillet, Linda Rossi, Laurence Goumy, Claire Ballot, Héloïse Reumaux, Centre Hospitalier de Belfort (Service de Rhumatologie), CH Belfort-Montbéliard, Service d'Onco-Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nancy, hôpital des Enfants [CHU Bordeaux], Pédiatrie hospices civils de Lyon, hôpital Femme-Mère-Enfant, Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Pédiatrique, CHU Nîmes, France, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service de Pédiatrie Générale [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Rhumatologie Pédiatrique, Centre Universitaire de Lille, Pediatric Rheumatology [Le Kremlin-Bicêtre], Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [Le Kremlin-Bicêtre] (CeRéMAIA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Rhumatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS
Abstract: Objectifs L’alliance therapeutique (AT) se definit comme l’engagement mutuel entre le soignant et le patient au cours du processus therapeutique. L’adhesion therapeutique est un enjeu majeur dans la prise en charge de l’arthrite juvenile idiopathique (AJI) et repose sur la forte capacite de l’enfant a suivre les traitements. Cette etude avait pour objectif d’evaluer l’association entre l’AT et l’adhesion therapeutique chez des patients atteints d’AJI. Methodes Etude observationnelle, transversale, multicentrique. Des enfants atteints d’AJI, âges de 8 a 16 ans ont ete inclus. Les enfants, leurs parents et les medecins ont complete le Helping Alliance Questionnaire (HAq-CP) pour mesurer l’AT. L’observance aux traitements a ete mesuree a l’aide du Child/Parent Adherence Report Questionnaire (CARQ & PARQ). Les donnees demographiques, les caracteristiques de la maladie, les traitements en cours et l’environnement social ont ete recueillis. La relation univariee entre l’AT et l’adhesion a ete mesuree a l’aide du coefficient de correlation de Pearson. L’analyse multivariee a utilise un modele de regression lineaire multiple. Resultats 119 patients ont ete inclus : 68,9 % de filles, l’âge moyen (ET) etait de 12,4 (2,9) ans, avec une duree de la maladie de 73,1 (48,2) mois. L’AJI etait en remission (52 %), de faible activite (32 %) et active (16 %). Les scores de l’AT etaient eleves (≥ 80/100) chez les enfants, les parents et les medecins. Le HAQ-CP a montre une forte correlation avec le CARQ (r = 0,31 ; p Conclusion L’AT exerce une forte influence sur l’adhesion therapeutique et pourrait jouer un role majeur dans l’efficacite du traitement.
Published: 2022
Full Text: View/download PDF

20. Clinical value of pre-transplant minimal residual disease in childhood lymphoblastic leukaemia: the results of the French minimal residual disease-guided protocol

Author: Elizabeth Macintyre, Pascale Schneider, Claire Galambrun, Cécile Pochon, Jean-Hugues Dalle, Pierre Bordigoni, Virginie Gandemer, Geneviève Margueritte, Gérard Michel, Patrick Lutz, Claudine Schmitt, Eva de Berranger, Emmanuel Oger, Hélène Cavé, François Demeocq, Marilyne Poirée, Nathalie Grardel, Jean-Michel Cayuela, Francoise Mechinaud, Pierre Rorhlich, Dominique Plantaz, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Pharmacologie [Rennes], CHU Pontchaillou [Rennes], Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université Paris Diderot - Paris 7 (UPD7), Service de Biochimie Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Laboratoire central d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Children's Cancer Center, The Royal Children's Hospital, Hôpital Civil, Hopital Civil, Service d'hématologie pédiatrique, CHU Clermont-Ferrand, Service d'hémato-immuno-oncologie pédiatrique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service Hématologie Infantile, CHU Grenoble, Unité de Transplantation Médullaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital d'enfants, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Oncology, Male, medicine.medical_specialty, Neoplasm, Residual, Multivariate analysis, Adolescent, medicine.medical_treatment, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Adjuvants, Immunologic, Immunologic, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Combined Modality Therapy, Humans, Cumulative incidence, Adjuvants, Prospective Studies, Prospective cohort study, Child, Preschool, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Remission Induction, Hematopoietic Stem Cell Transplantation, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Minimal residual disease, 3. Good health, Surgery, Transplantation, body regions, Treatment Outcome, Child, Preschool, 030220 oncology & carcinogenesis, Residual, Lymphoblastic leukaemia, Neoplasm, Female, business, 030215 immunology
Abstract: International audience; Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non-ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T-cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high-risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD \textless10(-3) and the 27 with MRD ≥10(-3) . Multivariate analysis identified sex match and MRD as being significantly associated with 5-year survival. MRD ≥10(-3) compromised the 5-year cumulative incidence of relapse (43*6 vs. 16*7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre-transplant MRD is still a major predictor of outcome for ALL. The MRD-guided strategy resulted in survival for 72*3% of patients with MRD\textless10(-3) and 40*4% of those with MRD ≥10(-3).
Published: 2014
Full Text: View/download PDF

21. Prognosis of ETV6/RUNX1 leukemia relapses

Author: Gandemer, Virginie, Chevret, Sylvie, Petit, Arnaud, Vermylen, Christiane, Leblanc, Thierry, Michel, Gerard, Schmitt, Claudine, Lejars, Odile, Schneider, Pascale, Demeocq, Francois, Bader-Meunier, Brigitte, Bernaudin, Francoise, Perel, Yves, Auclerc, Marie-Francoise, Cayuela, Jean-Michel, Leverger, Guy, Baruchel, Andre, Service de médecine de l'enfant et de l'adolescent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Génétique Hématologique, Clinique Universitaire Saint-Luc, de Duve Institute, UCL, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'hémato-immuno-oncologie pédiatrique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Clermont-Ferrand, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital intercommunal de Créteil, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Laboratoire central d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], CHU Pontchaillou [Rennes], CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: relapse, hemic and lymphatic diseases, childhood leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, prognosis, ETV6/RUNX1, acute lymphoblastic
Abstract: International audience; Purpose. The prognosis of relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long term follow-up a retrospective study to address the outcome of ETV6/RUNX1-positive leukemia relapses.Design and Method. Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified as low or intermediate risk groups. Median follow-up after relapse was 54.2 months. All but three received a second-line salvage therapy and 16 underwent an allogeneic transplantation.Results. ETV6/RUNX1 greatly impacted on overall survival after relapse (3 year-survival= 64.7 % for positive versus 46.5 % for negative cases) (p= 0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (p=0.04). 81.4 % were late relapses, early combined or isolated extramedullar relapses. The 5-year survival rate of ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.6% when relapse occurred after 36 months (vs 34.9%). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome.Conclusions. We found an excellent outcome for ETV6/RUNX1-positive leukemia relapses occurring over 36 months post-diagnosis. Duration of first complete remission may thus be a guide to define the treatment strategy of ETV6/RUNX1-positive leukemia relapse.
Published: 2012
Full Text: View/download PDF

22. Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes

Author: Cécile, Martel, Michelle, Mollin, Sylvain, Beaumel, Jean Paul, Brion, Charles, Coutton, Véronique, Satre, Gaëlle, Vieville, Mary, Callanan, Christine, Lefebvre, Alexandra, Salmon, Anne, Pagnier, Dominique, Plantaz, Cécile, Bost-Bru, Laurence, Eitenschenck, Isabelle, Durieu, Daniel, Floret, Claire, Galambrun, Hervé, Chambost, Gérard, Michel, Jean-Louis, Stephan, Olivier, Hermine, Stéphane, Blanche, Nathalie, Blot, Hervé, Rubié, Guillaume, Pouessel, Stephanie, Drillon-Haus, Bernard, Conrad, Klara M, Posfay-Barbe, Zuzana, Havlicekova, Tamara, Voskresenky-Baricic, Kelecic, Jadranka, Maria Cristina, Arriazu, Luis Alberto, Garcia, Lamia, Sfaihi, Lamia Sfaihi Ben, Mansour, Pierre, Bordigoni, Marie José, Stasia, Conrad, Bernard, Posfay Barbe, Klara, Université Joseph Fourier - Grenoble 1 (UJF), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Maladie Infectieuse, CHU Grenoble, Service de Médecine Interne et Maladies Infectieuses, AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Hématologie Infantile, Service de Médecine Interne - Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Services de Réanimation et d'urgences Pédiatriques, Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie pédiatrique, CHU Saint-Etienne, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'immuno-hématologie pédiatrique [CHU Necker], Service de Pédiatrie Néonatologique, CH Sallanches, Unité d'Hémato-Oncologie, Hôpital des Enfants, Service de Pédiatrie, CH de Roubaix, Service de Pédiatrie et Onco-hématologie, CHU Strasbourg, DiaGena, MCL Niederwangen, Pediatric Infectious Diseases, University Hospital of Geneva, Department of Pediatrics, Comenius University [Bratislava], Pediatric Clinic Klaiceva, University Hospital Center Zagreb, Department of Pediatric and Pneumology, Hospital Privado Comunidad Argentina, Service de pédiatrie, Hedi Chaker Hospital [Sfax], Service de Médecine Infantile II [CHRU Nancy], Université Joseph Fourier - Grenoble 1 ( UJF ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), AGeing and IMagery ( AGIM ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Comenius University, CHU Hédi Chaker, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Comenius University in Bratislava
Subjects: Male, MESH: Membrane Glycoproteins, MESH : Membrane Glycoproteins, MESH : Child, Preschool, Granulomatous Disease, Chronic, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Exon, 0302 clinical medicine, MESH : Child, MESH: Granulomatous Disease, Chronic, MESH: Child, Immunology and Allergy, Missense mutation, MESH : Female, MESH: NADPH Oxidase, Child, Genetics, 0303 health sciences, Mutation, Membrane Glycoproteins, ddc:618, MESH : Infant, MESH: Infant, Stop codon, 3. Good health, 030220 oncology & carcinogenesis, Child, Preschool, NADPH Oxidase 2, NADPH Oxidase/genetics, Female, MESH : Mutation, MESH: Mutation, MESH : Male, Immunology, Nonsense mutation, Biology, Frameshift mutation, 03 medical and health sciences, MESH : NADPH Oxidase, cronic granulomatous disease, genetic mutations, medicine, Humans, CYBB, 030304 developmental biology, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Humans, Point mutation, MESH : Humans, MESH: Child, Preschool, NADPH Oxidases, Infant, Membrane Glycoproteins/genetics, Granulomatous Disease, Chronic/genetics, Molecular biology, MESH: Male, MESH : Granulomatous Disease, Chronic, MESH: Female
Abstract: International audience; Chronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and cannot produce superoxide anions. The most common form is caused by mutations in CYBB encoding gp91phox. We investigated 24 CGD patients and their families. Twenty-one mutations in CYBB were classified as X91(0), X91(+) or X91(-) variants according to cytochrome b (558) expression. Point mutations in encoding regions represented 50 % of the mutations found in CYBB, splice site mutations 27 %, deletions and insertions 23 %. Eight mutations in CYBB were novel leading to X91(0)CGD cases. Two of these were point mutations: c493G>T and a double mutation c625C>G in exon 6 and c1510C>T in exon 12 leading to a premature stop codon at Gly165 in gp91phox and missense mutations His209Arg/Thr503Ile respectively. Two novel splice mutations in 5'intronic regions of introns 1 and 6 were found. A novel deletion/insertion c1024_1026delCTG/insT results in a frameshift introducing a stop codon at position 346 in gp91phox. The last novel mutation was the insertion of a T at c1373 leading to a frameshift and a premature stop codon at position 484 in gp91phox. For the first time the precise size of two large mutations in CYBB was determined by array-comparative genomic hybridization and carriers' status were evaluated by multiplex ligation-dependent probe amplification assay. No clear correlation between clinical severity and CYBB mutations could be established. Of three mutations in CYBA, NCF1 and NCF2 leading to rare autosomal recessive CGD, one nonsense mutation c29G>A in exon 1 of NCF2 was new.
Published: 2012
Full Text: View/download PDF

23. Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome

Author: André Baruchel, Yves Perel, Anne Hagemejier, Guy Leverger, Judith Landman-Parker, Paola Ballerini, Virginie Gandemer, François Sigaux, Gérard Michel, Claudine Schmitt, Vahid Asnafi, Jean Michel Cayuela, Sylvie Fasola, Marie Françoise Auclerc, Luc Douay, Thierry Leblanc, Myriam Labopin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'hématologie, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'onco-hématologie pédiatrique, hôpital Sud, Service d'hématologie pédiatrique et oncologie, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie, Service d'oncologie et hématologie, Hôpital d'enfants, Department of Human Genetics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), supported by Chugai France (Dr. Thierry Guillot) and SFCE (Société Française des Cancers de l'Enfant)., Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Sud, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Catholic University of Leuven ( KU Leuven ), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), and De Villemeur, Hervé
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Oncology, Time Factors, Transcription, Genetic, MESH : Genotype, MESH : Child, Preschool, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, 0302 clinical medicine, MESH : Child, hemic and lymphatic diseases, MESH: Child, Gene expression, Genotype, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia-Lymphoma, Adult T-Cell, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Medicine, MESH : Female, MESH : Homeodomain Proteins, MESH: Leukemia-Lymphoma, Adult T-Cell, Child, Regulation of gene expression, 0303 health sciences, MESH : Prognosis, Hematology, Hazard ratio, MESH : Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Follow-Up Studies, MESH: Gene Expression Regulation, Neoplastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Adult, Prognosis, MESH : Survival Rate, MESH: Infant, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, NUP214-ABL1, Child, Preschool, 030220 oncology & carcinogenesis, outcome, Female, France, TLX3/HOX11L2, MESH : Time Factors, Adult, medicine.medical_specialty, Adolescent, MESH: Survival Rate, MESH : Gene Expression Regulation, Neoplastic, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Prognosis, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Adolescent, Internal medicine, MESH: Homeodomain Proteins, Humans, MESH : France, Survival rate, 030304 developmental biology, Homeodomain Proteins, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, business.industry, MESH: Transcription, Genetic, MESH : Humans, MESH: Time Factors, MESH: Child, Preschool, Infant, MESH : Transcription, Genetic, childhood T-cell acute lymphoblastic leukemia, MESH : Follow-Up Studies, MESH: Adult, MESH : Leukemia-Lymphoma, Adult T-Cell, MESH: Male, MESH: France, El Niño, Fusion transcript, Immunology, SIL-TAL1, business, MESH: Female, Follow-Up Studies
Abstract: International audience; BACKGROUND: The prognostic value of the ectopic activation of TLX3 gene expression, a major oncogenetic event associated with pediatric T-cell acute lymphoblastic leukemia, is controversial. Likewise, the frequency and the prognostic significance in pediatric T-cell acute lymphoblastic leukemia of the newly characterized NUP214-ABL1 fusion transcript is not yet clear. DESIGN AND METHODS: Two hundred children with T-cell acute lymphoblastic leukemia were treated in the French FRALLE-93 study from 1993 to 1999. The expression of TLX3, TLX1 and SILTAL1 genes was analyzed in samples from 92 patients by real-time quantitative reverse transcriptase polymerase chain reaction. Most of these samples were further studied for NUP214-ABL1 and CALM-AF10 fusion transcripts. RESULTS: The median follow-up was 7.9 years. At 5 years the overall survival (+/- standard deviation, %) was 62 (+/-3%) and leukemia-free survival was 58 (+/-3%). Patients with T-cell acute lymphoblastic leukemia positive for TLX3 had a poorer survival compared to those with T-ALL negative for TLX3 (overall survival: 45+/-11% vs. 57+/-5%, p=0.049). In multivariate analysis, TLX3 expression was an independent adverse risk factor predicting relapse with a hazard ratio of 2.44 (p=0.017) and an overall survival with a hazard ratio of 3.7 (p=0.001). NUP214-ABL1 was expressed in 16.6% of patients with TLX3-positive T-ALL (3 of 18); all of the patients with this association died before completion of the treatment. SILTAL expression did not significantly affect the prognosis of patients with T-cell acute lymphoblastic leukemia. Only three of 92 patients expressed the TLX1 gene and all three are alive. CONCLUSIONS: TLX3 gene expression is an independent risk factor predicting poor survival in childhood T-cell acute lymphoblastic leukemia. When co-expressed with TLX3, NUP214-ABL1 transcripts may increase the risk of poor survival.
Published: 2008
Full Text: View/download PDF

24. Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy

Author: Guy Leverger, Florence Menegaux, Anne Lambilliotte, Philippe Beaune, Danièle Sommelet, André Baruchel, Stéphanie Bellec, Marie-Anne Loriot, Sandra Rebouissou, Catherine Bonaïti-Pellié, Jean Feunteun, Denis Hémon, Jacqueline Clavel, Kamila Kebaili, Brigitte Lescoeur, Kaniewski, Nadine, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toxicologie Moleculaire (U490), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Toxicologie Moleculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique épidémiologique et structures des populations humaines ( Inserm U535 ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Cancer Research, Epidemiology, MESH : Polymorphism, Genetic, MESH : Prenatal Exposure Delayed Effects, Physiology, EPHX1, MESH : Child, Preschool, Coffee, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Res, MESH: Pregnancy, MESH : Child, Pregnancy, Risk Factors, Polymorphism (computer science), MESH: Child, Genotype, Odds Ratio, MESH : Female, Child, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Glutathione Transferase, Genetics, 0303 health sciences, Leukemia, Smoking, MESH : Acute Disease, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, MESH: Case-Control Studies, 3. Good health, MESH: Cytochrome P-450 CYP1A1, Oncology, Child, Preschool, Prenatal Exposure Delayed Effects, 030220 oncology & carcinogenesis, Acute Disease, MESH: Acute Disease, Female, Adult, MESH : Case-Control Studies, MESH : Glutathione Transferase, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Leukemia, MESH: Polymorphism, Genetic, Cytochrome P-450 CYP1A1, medicine, Humans, MESH: Res, Allele, Risk factor, 030304 developmental biology, MESH: Glutathione Transferase, Polymorphism, Genetic, MESH: Humans, MESH : Humans, MESH : Leukemia, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, MESH: Coffee, MESH: Adult, Odds ratio, medicine.disease, MESH : Coffee, MESH: Odds Ratio, MESH : Pregnancy, MESH : Alcohol Drinking, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, MESH : Cytochrome P-450 CYP1A1, MESH : Odds Ratio, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, MESH: Alcohol Drinking, Blood sampling
Abstract: International audience; Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene-environment interactions were estimated using both case-control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0-4.9]) and with GSTM1 deletion (OR 2.3 [1.2-4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3-1.2] and 0.4 [0.1-1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.
Published: 2005

25. Incidence of childhood leukaemia and non-Hodgkin's lymphoma in France: National Registry of Childhood Leukaemia and Lymphoma, 1990-1999

Author: Stéphanie Bellec, Brigitte Nelken, Denis Hémon, Guy Leverger, Jacqueline Clavel, Marie-Françoise Auclerc, Etienne Vilmer, C Waterkeyn, André Baruchel, A. Goubin, Anne Auvrignon, Catherine Patte, Danièle Sommelet, Nathalie Philippe, F Perrillat-Menegaux, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe FRALLE, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Children´s Leukaemia Cooperative Group (CLCG), EORTC, LMB, Institut Gustave Roussy (IGR), Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service hématologie-oncologie pédiatrique, Hôpital Jeanne de Flandre [Lille], Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Registre National des Hémopathies malignes de l'Enfant (RNHE), Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Kaniewski, Nadine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Cancer Research, Pediatrics, Time Factors, MESH: Registries, Epidemiology, Disease, MESH: Research Support, Non-U.S. Gov't, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin, immune system diseases, MESH: Leukemia, Lymphocytic, Acute, hemic and lymphatic diseases, MESH: Child, Registries, 030212 general & internal medicine, MESH: Incidence, Child, education.field_of_study, Leukemia, Incidence, Lymphoma, Non-Hodgkin, Incidence (epidemiology), Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Infant, 3. Good health, Childhood leukaemia, Haematopoiesis, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, France, medicine.medical_specialty, Adolescent, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Sex Factors, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Sex Factors, MESH: Leukemia, medicine, Humans, education, MESH: Adolescent, MESH: Humans, business.industry, MESH: Time Factors, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Infant, medicine.disease, MESH: Male, Non-Hodgkin's lymphoma, Lymphoma, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, National registry, business, MESH: Female, MESH: Child, Prescho
Abstract: International audience; The French National Registry of Childhood Leukaemia and Lymphoma (NRCL) covers the whole French mainland population aged less than 15 years (approximately 11 million children) for all childhood haematopoietic tumours since 1 January 1990, except Hodgkin's disease, which has been registered since 1 January 1999. During the period from 1990 to 1999, 5757 cases of leukaemia, lymphoma and myelodysplastic syndrome were registered in the NRCL, with an average of 2.5 sources per case. The age-standardized incidence rates per million per year were 43.1 for leukaemia (34.3 for acute lymphoblastic leukaemia, 7.1 for acute myeloblastic leukaemia, 0.6 for chronic myeloid leukaemia and 0.5 for chronic myelomonocytic leukaemia), 8.9 for non-Hodgkin's lymphomas and 6.7 for Hodgkin's disease. Down's syndrome was present in 110 cases of acute leukaemia (2.5%) and three cases of non-Hodgkin's lymphoma (0.3%). The incidence of acute lymphoblastic leukaemia showed a typical peak at age 2 years for girls and 3 years for boys. The incidence rates of leukaemia and non-Hodgkin's lymphoma did not show any temporal trends over the 10 year period.
Published: 2004

26. Acute childhood leukaemia and environmental exposure to potential sources of benzene and other hydrocarbons; a case-control study

Author: André Baruchel, Anne Lambilliotte, Etienne Vilmer, K Kebaili, Jacqueline Clavel, Danièle Sommelet, C Steffen, Guy Leverger, Denis Hémon, Marie-Françoise Auclerc, Anne Auvrignon, Secretariat, U754, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille], Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, MESH: Benzene, 010501 environmental sciences, 01 natural sciences, 0302 clinical medicine, Residence Characteristics, hemic and lymphatic diseases, MESH: Child, Epidemiology, Odds Ratio, Medicine, hydrocarbons, MESH: Residence Characteristics, MESH: Maternal Exposure, Child, Confounding, MESH: Infant, Newborn, Environmental exposure, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Case-Control Studies, MESH: Infant, MESH: Leukemia, Lymphocytic, Acute, L1, Maternal Exposure, 030220 oncology & carcinogenesis, Child, Preschool, leukaemia, Original Article, Female, epidemiology, France, environment, medicine.medical_specialty, MESH: Environmental Exposure, Occupational medicine, 03 medical and health sciences, Acute lymphocytic leukemia, Environmental health, MESH: Hydrocarbons, Humans, 0105 earth and related environmental sciences, childhood, Pregnancy, MESH: Humans, business.industry, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Case-control study, Infant, Newborn, Infant, Benzene, Odds ratio, Environmental Exposure, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: Aim: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia. Methods: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers. Results: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors. Conclusions: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association.
Published: 2004
Full Text: View/download PDF

27. High‐dose chemotherapy followed by autologous stem cell rescue in Wilms tumors: French report on toxicity and efficacy

Author: Isabelle Pellier, Hélène Sudour-Bonnange, Marie-Dominique Tabone, Claudia Pasqualini, Christophe Bergeron, Gudrun Scheleirmacher, Frédérique Dijoud, Aurore Coulomb-L'Hermine, Xavier Muracciole, Anne Notz-Carrere, Claire Freycon, Magali Morelle, Cécile Boulanger, Manon Delafoy, Arnauld Verschuur, Sabine Irtan, Estelle Thebaud, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Curie [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de radiothérapie - [Hôpital de la Timone - Hôpital Nord - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'oncologie pédiatrique [Institut Curie, Paris], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité d'oncologie pédiatrique [Centre Oscar Lambret, Lille], Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Service d'oncologie pédiatrique [CHU Nantes], Service d'Onco-Hématologie Pédiatrique [CHU Grenoble], Service d'Hémato-oncologie Pédiatrique [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Service d'Hématologie et Oncologie pédiatriques [CHRU Toulouse], Centre Hospitalier Régional Universitaire de Toulouse (CHRU Toulouse), Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de chirurgie viscérale pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service de pathologie [CHU Trousseau], Unité de Biostatistiques [Lyon], Centre Léon-Bérard : Centre de lutte contre le cancer de Lyon et Rhône-Alpes, and Département d'oncologie pédiatrique [Centre Léon Bérard, Lyon]
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Autologous Stem Cell Rescue, Adolescent, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Wilms Tumor, Young Adult, 03 medical and health sciences, High dose chemotherapy, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Young adult, Child, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Chemotherapy, business.industry, Stem Cells, Hematopoietic Stem Cell Transplantation, Wilms' tumor, Hematology, medicine.disease, Combined Modality Therapy, Kidney Neoplasms, 3. Good health, Respiratory failure, Child, Preschool, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Toxicity, Cohort, Female, business, 030215 immunology
Abstract: International audience; BackgroundHeterogeneous data have been reported on high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in Wilms tumors (WTs). We aimed to define its safety and efficacy in the French cohort, and to compare this management to current international recommendations.MethodsData prospectively collected from children, adolescents, and young adults with WT treated with HDCT/ASCR between 2000 and 2016 in French centers were retrospectively analyzed. Toxicity was reported according to CTCAE v4.03.ResultsFifty-four patients received HDCT/ASCR (first line, n = 13; recurrence, n = 41). Their median age at the time of ASCR was 5.3 years (range 2.2–21.6). Main nonhematological acute grades 3–4 toxicities were digestive and renal. No significant difference of toxicity rate was observed among HDCT regimens and schedules. Two patients died shortly after ASCR (renal and multiorgan failure), and one heavily pretreated patient died of late respiratory failure. The selection criteria applied to define those patients eligible for HDCT/ASCR retrospectively matched to those currently used in the International Society of Pediatric Oncology (SIOP) UMBRELLA protocol for 38 patients, with encouraging survival rates compared to published data. The objective response rate to HDCT was 21%, with a disease control rate after HDCT of 85%. After a median follow-up of 7 years, the 5-year event-free survival (EFS) and overall survival (OS) were 54% (95% CI: 32%–76%) and 62% (95% CI: 31%–82%) for frontline patients, and 57% (95% CI: 39%–71%) and 69% (95% CI: 52%–81%) at recurrence.ConclusionHDCT was feasible and showed encouraging results in well-defined settings. Data from the current prospective protocol will help to better evaluate HDCT impact on survival.
Published: 2021
Full Text: View/download PDF

28. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes

Author: Helder Fernandes, Guy Leverger, Vincent Barlogis, Yves Bertrand, Mohammed Zarhrate, Corinne Pondarré, E. Dore, Nathalie Cheikh, Elodie Colomb Bottollier, Caroline Thomas, Eric Jeziorski, Frédéric Rieux-Laucat, Fabienne Mazerolles, Y Perel, Capucine Picard, Pascale Blouin, Cécile Fourrage, Nicolas Garcelon, Aude Magerus-Chatinet, Marlène Pasquet, Sylvain Hanein, Benedicte Neven, Dominique Plantaz, Nathalie Aladjidi, Fanny Fouyssac, Thierry Leblanc, Jérémie Rosain, Alain Fischer, Marie-Claude Stolzenberg, Stéphane Ducassou, Sidonie Jacques, Frédéric Millot, Jérôme Hadjadj, Wadih Abou Chahla, Isabelle Pellier, Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Clinical Bioinformatics laboratory (Equipe Inserm U1163), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Hospices Civils de Lyon, Departement de Neurologie (HCL), Service d'Immuno-Hémato-Oncologie Pédiatrique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Rieux-Laucat, Frédéric, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Collège de France - Chaire Médecine expérimentale (A. Fischer), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Hôpital des Enfants, Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École Pratique des Hautes Études (EPHE), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hôpital Arnaud de Villeneuve, École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Collège de France (CDF), and Collège de France (CdF)
Subjects: Adult, Male, Evans syndrome, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, medicine.disease_cause, Biochemistry, Genetic determinism, LRBA, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Humans, Medicine, Child, 030304 developmental biology, Genetic testing, Autoimmune disease, 0303 health sciences, Mutation, medicine.diagnostic_test, business.industry, Infant, Cell Biology, Hematology, medicine.disease, Thrombocytopenia, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Child, Preschool, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Anemia, Hemolytic, Autoimmune, Autoimmune hemolytic anemia, business
Abstract: Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M− group). The M+ group displayed more severe disease than the M− group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.
Published: 2019
Full Text: View/download PDF

29. Allogeneic hematopoietic stem cell transplant outcomes for patients with dominant negative IKZF1/IKAROS mutations

Author: Asbjørg Stray-Pedersen, Nao Yoshida, Rebecca A. Marsh, Hye Sun Kuehn, Sergio D. Rosenzweig, Seiji Kojima, Claire Galambrun, Erinn S. Kellner, Vincent Barlogis, David Boutboul, Christa Krupski, Hans Christian Erichsen, Sylvain Latour, Immunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Division of Human Genetics and Division of Immune Deficiency and Bone Marrow Transplant, Cincinnati Children's Hospital, Cincinnati, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV]Life Sciences [q-bio], Immunology, Dominant negative, Graft vs Host Disease, Ikaros Transcription Factor, 03 medical and health sciences, 0302 clinical medicine, Text mining, Humans, Immunology and Allergy, Medicine, Child, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Hematopoietic Stem Cell Transplantation, Infant, 3. Good health, Treatment Outcome, Child, Preschool, 030220 oncology & carcinogenesis, Mutation, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Allogeneic hematopoietic stem cell transplant, business
Abstract: International audience
Published: 2019
Full Text: View/download PDF

30. Long-term event-free survival, chimerism and fertility outcomes in 234 patients with sickle-cell anemia younger than 30 years after myeloablative conditioning and matched-sibling transplantation in France

Author: Eliane Gluckman, Yves Bertrand, Karima Yakouben, Isabelle Thuret, Charlotte Jubert, Bénédicte Neven, Felipe Suarez, F. Bernaudin, Sébastien Maury, Catherine Paillard, Patrick Lutz, Société Française de Greffe de Moelle et de Thérapie Cellulaire, Jacques-Olivier Bay, Catherine Poirot, M. Kuentz, Claire Galambrun, Dominique Bories, Marie Robin, Jean-Paul Vernant, Pierre Rohrlich, Gérard Socié, Nicole Raus, Corinne Pondarré, Jean-Hugues Dalle, Régis Peffault de Latour, Jean-Pierre Vannier, Nathalie Dhedin, Centre Hospitalier Intercommunal de Créteil (CHIC), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), CHI Créteil, Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Nice (CHU Nice), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hématologie moléculaire [CHU Mondor], CHU Henri Mondor, Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Hôpital Civil, Hopital Civil, Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Service de Greffe de Moelle - Unité AJA, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Research Unit, Biology of Reproduction Unit, Paris, France, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Hemolytic anemia, medicine.medical_specialty, Transplantation Conditioning, Anemia, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Anemia, Sickle Cell, Gastroenterology, Chimerism, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Progression-free survival, Red Cell Biology & its Disorders, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Siblings, Hazard ratio, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Sickle cell anemia, Progression-Free Survival, 3. Good health, Transplantation, Fertility, 030220 oncology & carcinogenesis, France, business, Busulfan, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells 15 years (hazard ratio=4.37; P=0.002) and lower (5-15 vs. 20 mg/kg) ATG dose (hazard ratio=4.55; P=0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells
Published: 2020
Full Text: View/download PDF

31. Targeted screening failures in neonates with sickle cell disease in metropolitan France from 2005 to 2017: Number of cases, failure circumstances and health at diagnosis

Author: C. Pluchart, J. Remion, Service d'hématologie pédiatrique - CHU Reims, Centre Hospitalier Universitaire de Reims (CHU Reims), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Male, medicine.medical_specialty, Delayed Diagnosis, Anemia, Sickle Cell, Disease, 03 medical and health sciences, Neonatal Screening, 0302 clinical medicine, 030225 pediatrics, Humans, Medicine, Targeted screening, Diagnostic Errors, Intensive care medicine, False Negative Reactions, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Infant, Newborn, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 3. Good health, Metropolitan France, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Female, France, business, Follow-Up Studies
Abstract: International audience
Published: 2019
Full Text: View/download PDF

32. Mode of delivery in hemophilia: vaginal delivery and Cesarean section carry similar risks for intracranial hemorrhages and other major bleeds

Author: Andersson, Nadine G, Chalmers, Elizabeth A, Kenet, Gili, Ljung, Rolf, Makipernaa, Anne, Chambost, Hervé, PedNet Haemophilia Research Foundation, Skane University Hospital [Malmo], Lund University [Lund], Royal Hospital for Sick Children, Glasgow, Israeli Ministry of Health, Helsinki University Central Hospital, Unit of Coagulation Disorders, Division of Haematology, Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Prémilleux, Annick, HUS Comprehensive Cancer Center, University of Helsinki, Department of Oncology, and Van Geet, C
Subjects: Adult, medicine.medical_specialty, Intracranial Hemorrhages, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Hemophilia A, DIAGNOSIS, Infant, Newborn, Diseases, Article, 03 medical and health sciences, 0302 clinical medicine, AFFECTED INFANT, Pregnancy, Humans, Medicine, Registries, Family history, Science & Technology, Cesarean Section, business.industry, Vaginal delivery, Obstetrics, NEWBORNS, Incidence (epidemiology), MORTALITY, Infant, Newborn, Coagulation & its Disorders, Hematology, medicine.disease, 3. Good health, PREVALENCE, LIFE, [SDV] Life Sciences [q-bio], Mode of delivery, Multicenter study, Relative risk, 3121 General medicine, internal medicine and other clinical medicine, Female, business, Life Sciences & Biomedicine, 030215 immunology
Abstract: The optimal mode of delivery for a pregnant hemophilia carrier is still a matter of debate. The aim of the study was to determine the incidence of intracranial hemorrhage and other major bleeds in neonates with moderate and severe hemophilia in relationship to mode of delivery and known family history. A total of 926 neonates, 786 with severe and 140 with moderate hemophilia were included in this PedNet multicenter study. Vaginal delivery was performed in 68.3% (n=633) and Cesarean section in 31.6% (n=293). Twenty intracranial hemorrhages (2.2%) and 44 other major bleeds (4.8%) occurred. Intracranial hemorrhages occurred in 2.4% of neonates following vaginal delivery compared to 1.7% after Cesarean section (P=not significant); other major bleeds occurred in 4.2% born by vaginal delivery and in 5.8% after Cesarean section (P=not significant). Further analysis of subgroups (n=813) identified vaginal delivery with instruments being a significant risk factor for both intracranial hemorrhages and major bleeds (Relative Risk: 4.78-7.39; P
Published: 2019
Full Text: View/download PDF

33. Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia

Author: René Valéro, Maxime Guye, Bénédicte Gaborit, I. Abdesselam, Marie Maraninchi, Hervé Chambost, Marie-Christine Alessi, Béatrice Cousin, Monique Bernard, Sophie Béliard, Gérard Michel, Sandrine Visentin, Claire Oudin, Marion Nowicki, Pascal Auquier, Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Génie Civil et d'Ingénierie Environnementale (LGCIE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Centre Français des Porphyries, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hopital Louis Mourier - AP-HP [Colombes], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition (C2VN), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Waist, childhood AL, Endocrinology, Diabetes and Metabolism, adipocytes, [SDV]Life Sciences [q-bio], ectopic fat, Adipose tissue, 030209 endocrinology & metabolism, adipocyte, Gastroenterology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, metabolic syndrome, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, stéatose hépatique, Internal medicine, irradiation, hepatic steatosis, Liver fat, Nonalcoholic fatty liver disease, Internal Medicine, Medicine, leucemie, Acute leukemia, Endocrinology and metabolism, syndrome métabolique, lcsh:RC648-665, business.industry, Research, Total body irradiation, medicine.disease, graisse ectopique, 030220 oncology & carcinogenesis, protéine utérine, graisse corporelle, Endocrinologie et métabolisme, Lipodystrophy, Metabolic syndrome, business
Abstract: Background/objective The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children’s irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors. Design We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI. Subjects/methods Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. Results Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation. Conclusions These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.
Published: 2019
Full Text: View/download PDF

34. Pharmacokinetics and tissue diffusion of ganciclovir in mice and rats

Author: Pierre Gressens, Homa Adle-Biassette, Natacha Teissier, May Fakhoury, Evelyne Jacqz-Aigrain, Imene Boujemla, Marie Françoise Hurteaud, Michel N. Nassar, Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie Pédiatrique et Pharmacogénétique [Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie pédiatrique [Robert-Debré, Paris], Department of Division of Imaging Sciences and Biomedical Engineering [London], Centre for the Developing Brain [London], King‘s College London-St Thomas' Hospital [London]-King‘s College London-St Thomas' Hospital [London], This work was supported by the INSERM, Paris Diderot University, and Grace de Monaco Foundation., and Teissier, Natacha
Subjects: 0301 basic medicine, Ganciclovir, Mouse, ganciclovir, medicine.medical_treatment, Intraperitoneal injection, Biological Availability, Pharmacology, Antiviral Agents, Injections, Blood cell, Mice, 03 medical and health sciences, Pharmacokinetics, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Animals, Tissue Distribution, Platelet, business.industry, Age Factors, Transplacental, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Pathophysiology, Rats, congenital CMV, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 030104 developmental biology, medicine.anatomical_structure, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Sensorineural hearing loss, business, Biomarkers, medicine.drug
Abstract: Background Congenital cytomegalovirus (CMV) infection is the leading infectious cause of birth defects, mental retardation and non-genetic sensorineural hearing loss. Murine models have been developed in order to understand the pathophysiological mechanisms underlying these lesions. These models are being proposed for the validation of therapeutic protocols for clinical use. The aim of this preclinical study was to assess the pharmacokinetics of the reference antiviral molecule, ganciclovir, in order to optimize these protocols and confirm the diffusion of the molecule to the appropriate target zones. Methods Transplacental and intracochlear diffusion of ganciclovir was evaluated in mice and rats. Pharmacokinetics was assessed in adult mice and pups after 5 consecutive days of intraperitoneal injection of ganciclovir. The occurrence of hematological side effects of ganciclovir was evaluated in the different blood cell lineages. Results In adult rats, the intracochlear diffusion of ganciclovir was shown to achieve the same concentration as in blood. In gestating mice, transplacental diffusion was observed, with a fetal-to-maternal blood ratio of 0.5. In newborn mice, the plasma concentration profile of ganciclovir showed a peak at 2 h followed by a gradual decrease. In adult mice, the concentration peaked at 1 h, but became undetectable by 2 h after injection. Counts of white blood cells, red blood cells and platelets decreased significantly in ganciclovir-treated newborn mice. Conclusion Our data provide evidence for the intracochlear diffusion of the molecule, which may be relevant for the treatment of sensorineural hearing loss in congenitally-infected children.
Published: 2016
Full Text: View/download PDF

35. Impaired muscular fat metabolism in juvenile idiopathic arthritis in inactive disease

Author: Emmanuelle Rochette, Pierre Bourdier, Bruno Pereira, Stéphane Echaubard, Corinne Borderon, Nicolas Caron, Aurélie Chausset, Daniel Courteix, Solenne Fel, Justyna Kanold, Justine Paysal, Sébastien Ratel, Nadège Rouel, Catherine Sarret, Daniel Terral, Alexandra Usclade, Etienne Merlin, Pascale Duché, Rochette, Emmanuelle, Centre Hospitalier Universitaire de Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Clermont Auvergne (UCA), Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Délégation de la Recherche Clinique et Innovations, Unité CRECHE, Centre d’Investigation Clinique 1405 (CIC), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine, Laboratoire Impact de l’Activité Physique sur la Santé, Université de Toulon (UTLN), CHU Clermont-Ferrand, Impact de l'Activité Physique sur la Santé (IAPS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), ProdInra, Archive Ouverte, Pôle Pédiatrie, Centre Hospitalier Universitaire [Rennes], Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques - Clermont Auvergne (AME2P), Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS-Université Clermont Auvergne (UCA), Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Pédiatrie Générale Multidisciplinaire, Centre Hospitalier Universitaire Estaing, Service Pédiatrie, Service d'hématologie pédiatrique, CHU Clermont-Ferrand-CIC Inserm 501, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Service de Pédiatrie Générale, CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Pharmacologie Clinique-CHU Gabriel-Montpied, and UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Arthritis, physical activity, Carbohydrate metabolism, lcsh:Physiology, Incremental exercise, 03 medical and health sciences, 0302 clinical medicine, Lipid oxidation, Physiology (medical), Internal medicine, Heart rate, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Juvenile, Respiratory system, ComputingMilieux_MISCELLANEOUS, Physiologie, Original Research, 030203 arthritis & rheumatology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, lcsh:QP1-981, business.industry, Lipid metabolism, fat oxidation, medicine.disease, 030104 developmental biology, Endocrinology, pediatric, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, inflammation, physiology, [SDV.IMM]Life Sciences [q-bio]/Immunology, metabolism, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives: The objective of this study was to evaluate muscular metabolic function in children with inactive juvenile idiopathic arthritis (JIA). Methods: Fifteen children with inactive JIA and fifteen healthy controls were matched by sex, biological age, and Tanner stage. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates. Results: Between the two groups, heart rate values and carbohydrate oxidation rates were the same, regardless of the relative intensity of exercise. Lipid oxidation rates were lower in JIA patients, regardless of the percentage of VO2 peak (p < 0.05). Respiratory exchange ratios beyond 50% of VO2 peak were higher in patients with JIA (p < 0.05). Respective maximal fat oxidation rates (MFO) for controls and children with JIA were 218.7 +/- 92.2 vs. 157.5 +/- 65.9 mg . min(-1) (p = 0.03) and 4.9 +/- 1.9 vs. 3.4 +/- 1.2 mg . min(-1) . kg(-1) (p = 0.04). There was no difference between the two groups in heart rate, percentage of VO2 peak, or power of exercise to achieve MFO. Controls reached their MFO at an exercise power significantly higher than did JIA subjects (42.8 +/- 16.8 and 31.9 +/- 9.8 W, p = 0.004). Conclusion: Children with JIA show metabolic disturbance during exercise, even when the disease is considered inactive. This disturbance is seen in a lower lipid oxidation rate during submaximal exercise.
Published: 2019
Full Text: View/download PDF

36. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

Author: Nizar Mahlaoui, Capucine Picard, Perrine Bach, Laurence Costes, Virginie Courteille, Anja Ranohavimparany, Alexandre Alcaïs, Jean-Philippe Jais, Alain Fischer, Christine Bellanné-Chantelot, Jacinta Bustamante, Sylvie Chollet-Martin, Christian Drouet, Véronique Fremeaux-Bacchi, Caroline Kannengiesser, Virginie Girardin, Nathalie Lambert, Valérie Proulle, Jérémie Rosain, Marie José Stasia, Dominique Stoppa Lyonnet, Ioannis Theodorou, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Emilie Catherinot, Nathalie Cheikh, Sarah Cohen-Beaussant, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Geneviève de Saint Basile, Catherine Devoldere, Anne Deville, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, David Launay, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Dalila Nouar, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Service de Biostatistique et Informatique Médicale, Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), the Study Center of Primary Immunodeficiencies, CHU Necker - Enfants Malades [AP-HP], Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Tronche, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hématogoie pédiatrique, hôpital Sud, SIGNAL-IMAGE-COMMUNICATION (SIC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses, CHU Grenoble, Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Foch [Suresnes], Service de pédiatrie (CHU de Dijon), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Service d'Immunologie Clinique et de Médecine Interne, Centre National de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Claude Huriez [Lille], CHU Lille, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, cellules dendritiques et greffes (JE 2448), Université de Tours (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine interne, maladies infectieuses, immunologie clinique, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d’Hémato-Oncologie Pédiatrique, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Internal Medicine, Paris, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Clermont-Ferrand, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], American Memorial Hospital, American Memory Hospital, Department of Clinical Immunology, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Hématologie Infantile, CHU Amiens-Picardie, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Médecine Interne, Immunologie clinique et maladies infectieuses [CHU Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Clinical Haematology, CHU Hôtel-Dieu, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], French Ministry of Health, LFB, GlaxoSmithKlineGlaxoSmithKline, CSL BehringCSL Behring, ShireShire, Octapharma, Binding Site, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Chaire Médecine expérimentale (A. Fischer), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GREPI, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie pédiatrique, CHU Toulouse [Toulouse], CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de médecine de l'enfant et de l'adolescent, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose et Progression tumorale (CRCNA / Equipe 9), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Service de médecine interne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Tours, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], McGill University, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Amiens (CHU), centre hospitalier universitaire amiens, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: 0301 basic medicine, Primary Immunodeficiency Diseases, medicine.medical_treatment, Genetic counseling, Immunology, Genomics, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Genotype, Humans, Immunology and Allergy, Medicine, Genetic Testing, Registries, Retrospective Studies, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Common variable immunodeficiency, Retrospective cohort study, medicine.disease, Phenotype, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Identification (biology), France, business, 030215 immunology
Abstract: International audience; To the Editor:Since the mid-1980s, continuous progress in genetics and genomics has accelerated the rapid identification of causative genetic variants leading to primary immunodeficiencies (PIDs; >300 genes),1 with the noticeable exception of B-cell disorders, such as common variable immunodeficiency (CVID). The identification of these mutations not only validates a clinical diagnosis but also is useful in several other respects (more accurate prognosis on phenotype/genotype correlation, targeted therapy, and genetic counseling). [...]
Published: 2019
Full Text: View/download PDF

37. Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

Author: Bensussan, Armand, Janela, Baptiste, Thonnart, Nicolas, Bagot, Martine, Musette, Philippe, Ginhoux, Florent, Marie-Cardine, Anne, Balligand, Laura, Galambrun, Claire, Sirvent, Anne, Roux, Clémence, Pochon, Cécile, Bruno, Bénédicte, Jubert, Charlotte, Loundou, Anderson, Esmiol, Sophie, Yakoub-Agha, Ibrahim, Forcade, Edouard, Paillard, Catherine, Marie-Cardine, Aude, Plantaz, Dominique, Gandemer, Virginie, Blaise, Didier, Rialland, Fanny, Renard, Cecile, Seux, Mylène, Baumstarck, Karine, Mohty, Mohamad, Dalle, Jean-Hugues, Michel, Gérard, CCSD, Accord Elsevier, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Jeanne de Flandre [Lille], Université de Lille, CHU Bordeaux [Bordeaux], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), CHU Marseille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Strasbourg, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré, Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de médecine (AMU MED), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Pasteur [Nice] (CHU), Institut d'Histoire de la Pensée Classique (IHPC), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Service Hématologie Infantile, CHU Grenoble, Hématogoie pédiatrique, hôpital Sud, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Cryopic, Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Sud, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Cord blood unit, Disease, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Prospective Studies, Young adult, Children, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Transplantation, Acute leukemia, business.industry, Minimal residual disease, Stem cell transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 3. Good health, body regions, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Double-Unit Umbilical Cord Blood Transplantation, Cord blood, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, business, 030215 immunology, Young adults
Abstract: International audience; We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10-4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (
Published: 2019
Full Text: View/download PDF

38. Very long-term molecular follow-up of minimal residual disease in patients with neuroblastoma

Author: Nadège Rouel, Dominique Plantaz, Justyna Kanold, Philippe Vago, Andrei Tchirkov, Victoria Grèze, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Service d'hématologie pédiatrique, and CHU Clermont-Ferrand-CIC Inserm 501
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Neoplasm, Residual, medicine.medical_treatment, Lymphocyte, Aftercare, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, neuroblastoma, 0302 clinical medicine, Neuroblastoma, Internal medicine, Biomarkers, Tumor, Medicine, Humans, Clinical significance, RNA, Messenger, Child, Chemotherapy, business.industry, qRT-PCR, Hematology, medicine.disease, Minimal residual disease, 3. Good health, Transplantation, 030104 developmental biology, Real-time polymerase chain reaction, medicine.anatomical_structure, long-term molecular follow-up, 030220 oncology & carcinogenesis, Child, Preschool, Pediatrics, Perinatology and Child Health, minimal residual disease, Female, Stem cell, Neoplasm Recurrence, Local, business
Abstract: International audience; In high-risk neuroblastoma (HR-NB), the clinical significance of long-term minimal residual disease (MRD) monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for neuroblastoma mRNAs has not been investigated. We report long-term MRD follow-ups of four patients with HR-NB throughout the disease (diagnosis, remission, and relapse) and treatment course (chemotherapy, autologous and allogeneic stem cell transplantation, and donor lymphocyte and natural killer cell infusions). The results showed the stability of mRNA marker expression after different treatments and demonstrated their validity to predict relapse and assess therapeutic response. This opens up the possibility of investigating the utility of long-term molecular monitoring of MRD in prospective multicenter studies.
Published: 2018
Full Text: View/download PDF

39. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond–like syndrome

Author: Aline Schmidt, Felipe Suarez, Eric Oksenhendler, Barbara Schmaltz-Panneau, Philippe Bensaid, Jean Donadieu, Gérard Pierron, Yves Bertrand, Aurélie Docet, Blandine Beaupain, Vincent Barlogis, Frédéric Bauduer, Séverine Clauin, Christine Bellanné-Chantelot, Isabelle Plo, Isabelle Callebaut, Nathalie Aladjidi, Françoise Mazingue, Sylvie Souquere, Iléana Antony-Debré, Cécile Stoven, Thuan Chong Quah, Isabelle Pellier, Caroline Marty, Hubert Journel, Thierry Leblanc, Marie Ouachee, Gandhi-Laurent Damaj, Liana Carausu, Claire Fieschi, Odile Fenneteau, Véronique Saada, Claire Galambrun, Odile Boespflug-Tanguy, Marlène Pasquet, Brigitte Nelken, William Vainchenker, Claire Berger, Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Hematology, Centre Hospitalier Universitaire (CHU), Faculté de Médecine, University of Normandie Caen, Department of Pediatric Hematology and Immunology, Robert Debré Hospital, AP-HP, Paris, Department of Pediatric Hematology, Immunology and Oncology, CHU, Angers, Department of Pediatrics, CHU La Réunion, Groupe Hospitalier Sud Réunion, Physiologie et physiopathologie des rétrovirus endogènes et infectieux (RETRO-ENDO), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Unit of Pediatric Hematology, Centre d'Investigation Clinique 1401INSERM Centre d'Investigation Clinique Plurithématique, CHU Bordeaux, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Côte Basque, Bayonne, Department of Pediatrics, Centre Hospitalier Argenteuil, Argenteuil, Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Department of Pediatric Hematology and Oncology, CHU, Saint-Etienne, Pediatric Hematology and Oncology Institute, Lyon, Department of Pediatric Hematology and Oncology, CHU Brest, Department of Clinical Immunology, Saint-Louis Hospital, AP-HP, Paris, Service d'Hématologie pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Hematology, CHU, Angers, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Department of Pediatric Hematology and Oncology, CHRU, Lille, Department of Pediatrics, National University Hospital, Singapore, Service d'hématologie-oncologie adultes, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Institut of Pediatric Hematology and Oncology, Lyon, Hématologie pédiatrique, CHU Toulouse [Toulouse], Laboratory of Hematology, Gustave Roussy, Villejuif, Department of Hematology, Necker-Enfants Malades University Hospital, AP-HP, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Paris Descartes, CNRS UMR9196, Gustave Roussy, Villejuif, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Département de biologie et pathologie médicales [Gustave Roussy], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Paris Descartes - Paris 5 (UPD5), Rétrovirus endogènes et éléments rétroïdes des eucaryotes supérieurs (UMR 9196), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de la Côte Basque (CHCB), National University of Singapore (NUS), Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Gene knockdown, Shwachman–Diamond syndrome, Mutation, business.industry, [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Neutropenia, medicine.disease, medicine.disease_cause, Biochemistry, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Membrane protein, Unfolded protein response, medicine, Cancer research, Congenital Neutropenia, business, Exocrine pancreatic insufficiency, ComputingMilieux_MISCELLANEOUS
Abstract: Congenital neutropenias (CNs) are rare heterogeneous genetic disorders, with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and 1 autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with 7 distinct germ line SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life, and required long-term granulocyte colony-stimulating factor therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n = 5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n = 3). The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation, and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54-mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54-mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry.
Published: 2018
Full Text: View/download PDF

40. Treatment with cyclosporin in auto‐immune cytopenias in children: The experience from the French cohort OBS'CEREVANCE

Author: Yves Bertrand, Marlène Pasquet, Brigitte Nelken, Guy Leverger, Helder Fernandes, Nathalie Aladjidi, Mathilde Penel Page, Thierry Leblanc, Clara Libbrecht, Gérard Michel, Isabelle Pellier, Eric Jeziorski, Y Perel, Corinne Armari-Alla, Djamel Kherfellah, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Tronche, Department of Pediatric Hematology and Oncology, CHRU, Lille, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service d'hématologie pédiatrique et oncologie, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, and Service d'Hémato-oncologie Pédiatrique
Subjects: Pediatrics, medicine.medical_specialty, Evans syndrome, business.industry, [SDV]Life Sciences [q-bio], Hematology, medicine.disease, Auto immune, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Cohort, medicine, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: International audience
Published: 2018
Full Text: View/download PDF

41. Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study

Author: Noémie Resseguier, Natacha Rosso-Delsemme, Any Beltran Anzola, Karine Baumstarck, Vanessa Milien, Laurent Ardillon, Sophie Bayart, Claire Berger, Marie-Anne Bertrand, Christine Biron-Andreani, Annie Borel-Derlon, Sabine Castet, Pierre Chamouni, Ségolène Claeyssens Donadel, Emmanuelle De Raucourt, Dominique Desprez, Céline Falaise, Birgit Frotscher, Valérie Gay, Jenny Goudemand, Yves Gruel, Benoît Guillet, Annie Harroche, Abel Hassoun, Yoann Huguenin, Thierry Lambert, Aurélien Lebreton, Anne Lienhart, Michèle Martin, Sandrine Meunier, Fabrice Monpoux, Guillaume Mourey, Claude Negrier, Philippe Nguyen, Placide Nyombe, Caroline Oudot, Brigitte Pan-Petesch, Benoît Polack, Anne Rafowicz, Antoine Rauch, Delphine Rivaud, Pascale Schneider, Alexandra Spiegel, Cecile Stoven, Brigitte Tardy, Marc Trossaërt, Jean-Baptiste Valentin, Stéphane Vanderbecken, Fabienne Volot, Annelise Voyer-Ebrard, Bénédicte Wibaut, Tanguy Leroy, Thomas Sannie, Hervé Chambost, Pascal Auquier, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hématogoie pédiatrique, hôpital Sud, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier de Versailles André Mignot (CHV), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre Hospitalier Chambéry, Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Hôpital Morvan [Brest], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hémato-immuno-oncologie pédiatrique [Rouen], Groupe de recherche sur la thrombose, pharmacologie des antithrombotiques et situations à risque (GRT), Université Jean Monnet - Saint-Étienne (UJM), Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Santé Publique, Université de la Méditerranée - Aix-Marseille 2, Ministère des Affaires Sociales et de la Santé, Filière MHEMO, Université Aix-Marseille, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Hôpital Sud, Centre hospitalier de Versailles André-Mignot, 177, rue de Versailles, 78150 Le Chesnay, France, parent, Université de Tours, Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), CHU de Nancy - Hôpitaux de Brabois, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Jonchère, Laurent
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Activities of daily living, Cross-sectional study, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Academic Performance, Protocol, Early childhood, adherence, adolescents, Young adult, ComputingMilieux_MISCELLANEOUS, Qualitative Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, transition, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Patient Satisfaction, Female, Family Relations, France, Psychosocial, Attitude to Health, Haematology (Incl Blood Transfusion), Adult, young adults, medicine.medical_specialty, Transition to Adult Care, Adolescent, haemophilia, Haemophilia, Hemophilia A, 03 medical and health sciences, Young Adult, Quality of life (healthcare), 030225 pediatrics, medicine, Humans, business.industry, Protective Factors, medicine.disease, Treatment Adherence and Compliance, Cross-Sectional Studies, Social Class, Family medicine, Quality of Life, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration numberNCT02866526; Pre-results.
Published: 2018
Full Text: View/download PDF

42. Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia

Author: Jean Feuillard, Florent Dumezy, Estelle Guérin, Kaoutar Allou, Marc Maynadié, André Baruchel, Christine Arnoulet, Francis Lacombe, Marie C. Béné, Orianne Wagner Ballon, Hélène Jouault, Groupe d'Etude Immunologique des Leucémies, Françoise Solly, Adrienne Delabarthe, Julien Guy, Lydia Campos, Norbert Ifrah, Pascale Lepelley, Hervé Dombret, Franck Geneviève, Claude Preudhomme, Service d'Hématologie [Bordeaux], CHU Bordeaux [Bordeaux], Hématologie de liaison avec Institut de Cancérologie de la Loire [CHU de Saint-Etienne], CHU Saint-Etienne, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie adulte [Hôpital de Saint Louis], CHU Saint Louis [APHP], Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire d'Hématologie Biologique (Hémato - ANGERS), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Registre des hémopathies malignes de Côte d'Or, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-oncologie adultes, Hematology Department, Université d'Angers (UA), Service d'Hématologie Clinique [Hôtel Dieu, Nantes], Hôtel-Dieu de Nantes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, Oncology, Cancer Research, Neoplasm, Residual, CD33, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 0302 clinical medicine, Risk groups, AML, hemic and lymphatic diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Prospective Studies, Child, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Boolean gates, medicine.diagnostic_test, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, Middle Aged, Prognosis, 3. Good health, Leukemia, Myeloid, Acute, MRD, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Good prognosis, Adult, medicine.medical_specialty, Adolescent, Acute myeloblastic leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, survival, Disease-Free Survival, Immunophenotyping, Flow cytometry, Young Adult, 03 medical and health sciences, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Time point, Aged, business.industry, flow cytometry, Infant, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Minimal residual disease, body regions, business, 030215 immunology
Abstract: IF 3.118; International audience; The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10-2 (the classical morphological threshold to define remission) down to
Published: 2018
Full Text: View/download PDF

43. Combined Immunodeficiency in Patients With Trichohepatoenteric Syndrome

Author: Vély, Frédéric, Barlogis, Vincent, Marinier, Evelyne, Coste, Marie-Edith, Dubern, Béatrice, Dugelay, Emmanuelle, Lemale, Julie, Martinez-Vinson, Christine, Peretti, Noël, Perry, Ariane, Bourgeois, Patrice, Badens, Catherine, Goulet, Olivier, Hugot, Jean-Pierre, Farnarier, Catherine, Fabre, Alexandre, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie pédiatrique [AP-HM Hôpital de la Timone], Assistance Publique - Hôpitaux de Marseille (APHM)-Université de la Méditerranée - Aix-Marseille 2- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Pediatric Gastroenterology, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-Assistance Publique-Hopitaux de Paris-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de gastroentérologie et nutrition pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence maladie rare Thalassémie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Aix-Marseille Universite, French National Research Agency (ANR THE-RNA), ANR-15-CE17-0017,THE-RNA,Syndrome tricho-hépato-entérique des anomalies de la dégradation des ARN à un syndrome(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-Robert Debré Hospital-Assistance Publique-Hopitaux de Paris-Centre National de la Recherche Scientifique (CNRS), Gastroentérologie et Nutrition Pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institute of Cardiometabolism and Nutrition-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Origine, structure et évolution de la biodiversité, Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance Publique-Hopitaux de Paris-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: T-Lymphocytes, Immunology, diarrhée, Case Report, NK cells, Cohort Studies, Interferon-gamma, memory B cells, syndromic diarrhea/trichohepatoenteric syndrome, Humans, Lymphocyte Count, t cells, sKIV2L, SKIV2L, TTC37, immunodeficiency, T cells, B-Lymphocytes, Fetal Growth Retardation, immunodéficience, DNA Helicases, Immunologic Deficiency Syndromes, Infant, Newborn, Facies, Infant, Killer Cells, Natural, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Diarrhea, Infantile, Mutation, ttC37, Carrier Proteins, Hair Diseases, Immunologic Memory
Abstract: International audience; The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37, two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects. First, switched memory B lymphocytes count is very low. Second, IFN-gamma production by T and NK cells is impaired and associated with a reduced degranulation of NK cells. Third, T cell proliferation was abnormal in 3/6 TTC37-mutated patients. These three patients present with severe EBV infection and a transient hemophagocytosis which may be related to these immunological defects. Moreover, an immunological screening of patients with clinical features of SD/THE could facilitate both diagnosis and therapeutic management of these patients.
Published: 2018
Full Text: View/download PDF

44. Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A

Author: Christine Vinciguerra, Hervé Chambost, J. Goudemand, Yoann Huguenin, Virginie Demiguel, Patrice Lutz, Thierry Calvez, Chantal Rothschild, Alexandra Doncarli, Roseline d'Oiron, Yves Gruel, Vincent Dalibard, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hematologie, Université de Lille, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie et d'Oncologie pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Metronomics Global Health Initiative, Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS), Centre Hospitalier Universitaire de Lille (CHU de Lille), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Université Francois Rabelais [Tours], CHU de Bordeaux Pellegrin [Bordeaux], Hôpital de Hautepierre [Strasbourg], Centre Régional de Traitement de l'Hémophilie, Université de Lyon (COMUE), Université de Lille, Droit et Santé, Hôpitaux Universitaires Paris Sud, and ProdInra, Migration
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, [SDV]Life Sciences [q-bio], système de santé, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, Isoantibodies, law, immunogenicite, Public Health Surveillance, Cumulative incidence, Child, ComputingMilieux_MISCELLANEOUS, anticorps neutralisant, Immunoassay, biology, Incidence (epidemiology), [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Recombinant Proteins, 3. Good health, facteur de risque, Child, Preschool, Cohort, France, Antibody, hémophilie, medicine.medical_specialty, Hemophilia A, Article, 03 medical and health sciences, Internal medicine, qualité des soins, medicine, Humans, Adverse effect, Proportional Hazards Models, analyse de cohorte, inhibiteur, Factor VIII, business.industry, Proportional hazards model, Coagulation & Its Disorders, Antibodies, Neutralizing, Immunology, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, 030215 immunology, Hématologie
Abstract: International audience; A round one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more lifethreatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibitors in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated cohort of patients was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII < 1 IU/dL) first treated with one of the three factor VIII products studied. Details of product infusions, inhibitor assays and main fixed and time-varying inhibitor risk factors were recorded for the first 75 exposure days. Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated inhibitors) were analyzed by univariate and multivariate Cox models. We studied 395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane, Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors was significantly associated with the factor VIII product received (P= 0.005): the cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7-20.6) with Factane, 20.4% (95% CI: 14.0-29.1) with Advate, and 31.6% (95% CI: 23.5-41.7) with Kogenate Bayer. The low inhibitor incidence observed with Factane is concordant with recent findings from the SIPPET randomized trial. These consistent results from observational and experimental studies should lead to improved care for previously untreated patients and cost savings for healthcare systems worldwide.
Published: 2017
Full Text: View/download PDF

45. Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404)

Author: Sylvie Chevret, Suzanne Verlhac, Elisabeth Ducros-Miralles, Jean-Hugues Dalle, Regis Peffault de Latour, Mariane de Montalembert, Malika Benkerrou, Corinne Pondarré, Isabelle Thuret, Corinne Guitton, Emmanuelle Lesprit, Maryse Etienne-Julan, Gisèle Elana, Jean-Pierre Vannier, Patrick Lutz, Bénédicte Neven, Claire Galambrun, Catherine Paillard, Camille Runel, Charlotte Jubert, Cécile Arnaud, Annie Kamdem, Valentine Brousse, Florence Missud, Marie Petras, Lydia Doumdo-Divialle, Claire Berger, Françoise Fréard, Olivier Taieb, Elise Drain, Monique Elmaleh, Manuela Vasile, Yacine Khelif, Myriam Bernaudin, Philippe Chadebech, France Pirenne, Gérard Socié, Françoise Bernaudin, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Robert Debré, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université des Antilles (UA), CHU Pointe-à-Pitre/Abymes [Guadeloupe], CHU de la Martinique [Fort de France], Hôpital Charles Nicolle [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital de Hautepierre [Strasbourg], Université de Strasbourg (UNISTRA), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Saint-Etienne, Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), Université de Caen Normandie (UNICAEN), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Radiologie [Créteil], CHI Créteil, Hôpital Robert Debré Paris, Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pointe à Pitre], CHU Fort de France, Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Normandie Université (NU)-Normandie Université (NU), Service d'immuno-hématologie pédiatrique [CHU Necker], Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Groupe hospitalier Pellegrin, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Rouen, CHADEBECH, Philippe, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Jean Monnet - Saint-Étienne (UJM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Hôpital Avicenne, Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, Pediatrics, Ultrasonography, Doppler, Transcranial, medicine.medical_treatment, Hematopoietic stem cell transplantation, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Cognition, 0302 clinical medicine, Genetic randomization, Medicine, Pharmacology (medical), Prospective Studies, Child, Prospective cohort study, Stroke, General Medicine, Sickle cell anemia, 3. Good health, Cerebral vasculopathy, Research Design, Child, Preschool, 030220 oncology & carcinogenesis, Female, medicine.medical_specialty, Iron Overload, Randomization, Adolescent, Anemia, Sickle Cell, Chronic transfusion, 03 medical and health sciences, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, Blood Transfusion, Adverse effect, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Transfusion Reaction, Transcranial Doppler, medicine.disease, Surgery, Transplantation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: Background Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. Design DREPAGREFFE ( NCT01340404 ) is a multicenter, prospective trial enrolling SCA children younger than 15 years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥ 200 cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1 year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. Objectives To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. Discussion DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.
Published: 2017
Full Text: View/download PDF

46. Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Author: Céline Roman, Catherine Badens, Patrice Bourgeois, Marie-Edith Coste, Vincent Barlogis, Alexandre Fabre, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Génétique Moléculaire [Hôpital de la Timone - APHM], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique [AP-HM Hôpital de la Timone], Assistance Publique - Hôpitaux de Marseille (APHM)-Université de la Méditerranée - Aix-Marseille 2- Hôpital de la Timone [CHU - APHM] (TIMONE), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), and Gall, Valérie
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Antibiotics, Hematopoietic stem cell transplantation, Review, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, TTC37, very early onset IBD, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, SKIV2L, Internal medicine, medicine, Diminution, biology, business.industry, General Medicine, medicine.disease, Tricho-hepato-enteric syndrome, 3. Good health, Diarrhea, 030104 developmental biology, Parenteral nutrition, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein, 030211 gastroenterology & hepatology, Antibody, medicine.symptom, business, Rare disease
Abstract: International audience; Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare disease linked to the loss of function of either TTC37 or SKIV2L, two components of the SKI complex. It is characterized by a combination of 9 signs (intractable diarrhea, hair abnormalities, facial dysmorphism, immune abnormalities, IUGR/SGA, liver abnormalities, skin abnormalities, congenital heart defect and platelet abnormalities). We present a comprehensive review of the management of SD/THE and tested therapeutic regimens. A review of the literature was conducted in May 2017: 29 articles and 2 abstracts were included describing a total of 80 patients, of which 40 presented with mutations of TTC37, 14 of SKIV2L. Parenteral nutrition was used in the management of 83% of the patients and weaned in 44% (mean duration of 14.97 months). Immunoglobulins were used in 33 patients, but data on efficacy was reported for 6 patients with a diminution of infection (n = 3) or diarrhea reduction (n = 2). Antibiotics (n = 11) provided no efficacy. Steroids (n = 17) and immunosuppressant drugs (n = 13) were used with little efficacy and mostly in patients with IBD-like SD/THE. Hematopoietic stem cell transplantation (HSCT) was performed in 4 patients: 2 died, for one it corrected the immune defects but not the other features and for the last one, it provided only a partial improvement. Finally, no specific diet was effective except for some contradictory reports for elemental formula. In conclusion, the management of SD/THE mainly involves parenteral nutrition and immunoglobulin supplementation. Antibiotics, steroids, immunosuppressants, and HSCT are not recommended as principle treatments since there is no evidence of efficacy.
Published: 2017
Full Text: View/download PDF

47. Non syndromic childhood onset congenital sideroblastic anemia: A report of 13 patients identified with an ALAS2 or SLC25A38 mutation

Author: Thierry Leblanc, Hana Manceau, Fanny Fouyssac, J.F. Guichard, Nadja Jäkel, Patrick Lutz, Jean-Pierre Vannier, Cyrielle Fouquet, Fabienne Toutain, Mohamed Touati, Christiane Vermylen, Yves Perel, Marie-Amelyne Le Rouzic, Karim Maloum, Caroline Kannengiesser, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université de Bordeaux (UB), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Génétique Hématologique, Clinique Universitaire Saint-Luc, de Duve Institute, UCL, Médecine Interne-Pathologie Vasculaire - Immunologie Clinique, Hôpital Sainte Blandine, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pontchaillou [Rennes], Hôpital Civil, Hopital Civil, Service d'hématologie pédiatrique et oncologie, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), California Institute of Technology (CALTECH)-NASA, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN)
Subjects: Pathology, medicine.medical_specialty, Pediatrics, Iron Overload, [SDV]Life Sciences [q-bio], Mitochondrial Membrane Transport Proteins, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, medicine, Humans, Chelation therapy, Child, Adverse effect, Molecular Biology, Congenital sideroblastic anemia, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Cell Biology, Hematology, ALAS2, Anemia, Sideroblastic, 3. Good health, Phenotype, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Molecular Medicine, business, Non syndromic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 5-Aminolevulinate Synthetase, 030215 immunology
Abstract: The most frequent germline mutations responsible for non syndromic congenital sideroblastic anemia are identified in ALAS2 and SLC25A38 genes. Iron overload is a key issue and optimal chelation therapy should be used to limit its adverse effects on the development of children. Our multicentre retrospective descriptive study compared the strategies for diagnosis and management of congenital sideroblastic anemia during the follow-up of six patients with an ALAS2 mutation and seven patients with an SLC25A38 mutation. We described in depth the clinical, biological and radiological phenotype of these patients at diagnosis and during follow-up and highlighted our results with a review of available evidence and data on the management strategies for congenital sideroblastic anemia. This report confirms the considerable variability in manifestations among patients with ALAS2 or SLC25A38 mutations and draws attention to differences in the assessment and the monitoring of iron overload and its complications. The use of an international registry would certainly help defining recommendations for the management of these rare disorders to improve patient outcome.
Published: 2017
Full Text: View/download PDF

48. Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial

Author: Didier Bouscary, E. Tavernier, Mathilde Hunault-Berger, A Saad, Chantal Himberlin, Severine Lissandre, Christian Recher, Isabelle Luquet, F Orsini-Piocelle, M-A Couturier, Etienne Daguindau, N. Maillard, M C Béné, Caroline Bonmati, Francois Dreyfus, Martin Carre, J-P Marolleau, A Schmidt-Tanguy, Jacques Delaunay, Norbert Ifrah, Luc Fornecker, Mario Ojeda-Uribe, M Puyade, B. Choufi, J-F Hamel, Arnaud Pigneux, Marc Bernard, Anne Banos, L Sutton, V Rouillé, Laurence Sanhes, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie pédiatrique - CHU Reims, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CH Boulogne/Mer], CH Boulogne sur Mer, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Service d'Hématologie [CH Annecy], CH Annecy, Service d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [ CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service d'Hématologie et thérapie cellulaire [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie [CH Mulhouse], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'Hématologie [CH Perpignan], CH Perpignan, Service d'Hématologie [CH Argenteuil], CH Argenteuil, Service d'hématologie (CH de la Côte Basque), Centre Hospitalier de la Côte Basque (CHCB), Département d'Oncologie Médicale et d'Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie [CH Béziers], CH Béziers, Service d'Hématologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie Biologique [CHU Nantes], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Celgene for providing azacitidine, lenalidomide and financial support for the monitoring., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [Saint-Etienne], Institut de Cancérologie de la Loire [Saint-Etienne], Le CHCB, Centre Hospitalier de la Côte Basque, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Hématologie Biologique [CHU Toulouse], CHU Toulouse [Toulouse]-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Bernardo, Elizabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Oncology, Male, medicine.medical_specialty, Azacitidine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Internal medicine, Medicine, Humans, Lenalidomide, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Hematology, business.industry, Myeloid leukemia, Middle Aged, medicine.disease, 3. Good health, Lymphoma, Thalidomide, Survival Rate, Leukemia, Haematopoiesis, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Immunology, Female, business, 030215 immunology, medicine.drug
Abstract: Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial
Published: 2017
Full Text: View/download PDF

49. RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue

Author: Nathalie Rives, Nadège Rouel, Pascale Halle, Victoria Grèze, Florence Brugnon, Andrei Tchirkov, Justyna Kanold, F. Chambon, Bruno Pereira, Anne Sophie Gremeau, Service d'hématologie pédiatrique, CHU Clermont-Ferrand-CIC Inserm 501, Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire BDR CECOS - FIV AMP, CHU Estaing [Clermont-Ferrand], Gamétogenèse et Qualité du Gamète - ULR 4308 (GQG), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Lille, CHU Rouen, Normandie Université (NU), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Pathology, medicine.medical_specialty, fertility preservation, [SDV]Life Sciences [q-bio], testicular tissue, Biology, Andrology, 03 medical and health sciences, neuroblastoma, 0302 clinical medicine, Neuroblastoma, medicine, Azoospermia, 030219 obstetrics & reproductive medicine, Oncogene, Snap freezing, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell cycle, medicine.disease, Minimal residual disease, Molecular medicine, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, reverse transcription quantitative polymerase chain reaction, minimal residual disease, Bone marrow
Abstract: International audience; Neuroblastoma (NB) is the most common type of extracranial solid tumor in children with a high prevalence in toddlers. For childhood cancer survivors, preservation of reproductive potential is an important factor for quality of life. The optimization of NB minimal residual disease (MRD) detection in testicular tissue is crucial to evaluate the risk of malignant cell reintroduction. The first step in the present study was to assess the accuracy of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect tyrosine hydroxylase (TH), paired-like homeobox 2b (PHOX2B) and doublecortin (DCX) mRNA expression in frozen/thawed testicular tissues of patients with non-obstructive azoospermia (NOA) contaminated (in vitro model) with an increasing number of IMR-32 and SK-N-SH NB cells. Testicular tissues were frozen by slow or snap freezing. The second step was to determine the expression levels of these markers in testicular samples from 4 pre-pubertal males (2 with stage IV NB and 2 with non-NB malignancy). The yield of extracted RNA was similar in testicular samples frozen by slow or snap freezing. In the in vitro model, TH and DCX transcripts were detected in uncontaminated testicular tissues, whereas PHOX2B mRNA was not detected. There was a strong positive association between the number of NB cells used for contamination and PHOX2B transcript levels. For IMR-32 and SK-N-SH NB cell lines, specificity and sensitivity rates of detection were 100% for PHOX2B following in vitro contamination with 10 tumor cells. In testicular samples from pre-pubertal males with and without NB, PHOX2B mRNA expression was not observed, but high expression levels of TH and DCX mRNA were detected, which were similar to expression detected in the in vitro model. Among the markers used in blood and bone marrow for NB MRD studies, the detection of PHOX2B transcripts by RT-qPCR may provide an accurate assessment of NB cells in testicular tissues from males who require fertility preservation.
Published: 2017
Full Text: View/download PDF

50. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

Author: Yingying Wang, Chongsheng Qian, Bénédicte Bruno, Isabelle Clerc Urmes, Huili Cai, Patrice Ceballos, Cécile Pochon, Jean Hugues Dalle, Arnaud Campidelli, Marcelo De Carvalho Bittencourt, Nadine Petitpain, Danièle Bensoussan, Maud D'Aveni, Catherine Paillard, Hélène Jeulin, Loïc Reppel, Charlotte Jubert, Clément Cholle, Aude Marie-Cardine, Véronique Decot, Stephane Vigouroux, Claire Galambrun, Véronique Venard, Alexandra Salmon, Laurence Clement, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Unité de Thérapie Cellulaire et Tissulaire [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie [CHRU Nancy], Service de Virologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hôpital Jeanne de Flandre [Lille], Hôpital de Hautepierre [Strasbourg], Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Nicolle [Rouen], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Faculté de Pharmacie [Nancy], and Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], viruses, medicine.medical_treatment, Graft vs Host Disease, T-Cell Antigen Receptor Specificity, Hematopoietic stem cell transplantation, Immunotherapy, Adoptive, Adenovirus Infections, Human, 0302 clinical medicine, T-Lymphocyte Subsets, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, Viral Load, Allografts, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tissue Donors, 3. Good health, Treatment Outcome, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Interferon-γ-based immunomagnetic isolation, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, Viral load, Immunosuppressive Agents, Adult, Third party haploidentical donor, medicine.medical_specialty, Adolescent, T cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:RC254-282, Interferon-gamma, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Leukapheresis, Viremia, Adenovirus infection, Molecular Biology, Umbilical cord blood transplantation, Immunomagnetic Separation, lcsh:RC633-647.5, business.industry, Umbilical Cord Blood Transplantation, Research, Adenoviruses, Human, medicine.disease, Allogeneic stem cell transplantation, Transplantation, 030104 developmental biology, Graft-versus-host disease, Transplantation, Haploidentical, Immunology, Virus Activation, Adenovirus-specific T cells, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered). Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0469-0) contains supplementary material, which is available to authorized users.
Published: 2017
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

305 results on '"Service d'hématologie pédiatrique"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources