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1. Genomic analysis of primary and secondary myelofibrosis redefines the prognostic impact of ASXL1 mutations: a FIM study

Author: Jean-Claude Chomel, Jean-Christophe Ianotto, Laurane Cottin, Pierre Sujobert, Véronique Mansat-De Mas, Barbara Burroni, Vincent Cussac, Nathalie Jézéquel, Brigitte Dupriez, Bruno Cassinat, Emmanuelle Verger, Raouf Ben Abdelali, Dana Ranta, Damien Luque Paz, Olivier Kosmider, Olivier Mansier, Gabriel Etienne, Jerome Rey, Maxime Renard, Jean-Jacques Kiladjian, Fabienne Vacheret, Guillaume Denis, Anne Murati, Jérémie Riou, Pascal Mossuz, Françoise Boyer, Eric Lippert, Yannick Le Bris, Pascale Cony-Makhoul, Ivan Sloma, Anouk Walter-Petrich, Suzanne Tavitian, Stéphane Giraudier, Stéphane Girault, Aurélie Chauveau, Gérard Socié, François Girodon, Lydia Roy, Olivier Nibourel, Borhane Slama, Valérie Ugo, Margot Robles, Mathieu Wemeau, Bernardo, Elizabeth, 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 [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), UFR Santé [UNIV Angers], Université d'Angers (UA), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire de Biologie Cellulaire [AP-HP Hôpital Saint-Louis], 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie clinique [CHRU Brest], Service d'hématologie clinique [CH Lens], Centre Hospitalier de Lens, Service des maladies du sang [Angers], Service d'Hématologie [Bordeaux], CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), 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), Institut Bergonié [Bordeaux], UNICANCER, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Cancérologie Biologique [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie [CH Annecy], CH Annecy, Service d'hématologie biologique [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Perigueux, Laboratoire CERBA [Saint Ouen l'Aumône], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d’Hématologie [CHU Henri-Mondor - APHP], CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Hématologie et d'Immunologie [CHU Henri Mondor], 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), Service d'Hématologie [CH Perpignan], CH Perpignan, Centre Hospitalier de Roubaix, Service d'hématologie et d'Oncologie [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Avignon Université (AU), Service d’Onco-Hématologie et Médecine interne [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Rochefort, Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département d'anatomopathologie [CHU Cochin], Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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 Bordeaux (UB)-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)-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), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 biologique [CHU de Dijon], CHU Henri Mondor [Créteil], and Centre Hospitalier de Rochefort (CH Rochefort)
Subjects: Neuroblastoma RAS viral oncogene homolog, Oncology, medicine.medical_specialty, IDH1, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, IDH2, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Myelofibrosis, 030304 developmental biology, 0303 health sciences, Mutation, Acute leukemia, Myeloid Neoplasia, business.industry, Hazard ratio, Bayes Theorem, Hematology, Genomics, medicine.disease, Prognosis, 3. Good health, Repressor Proteins, Primary Myelofibrosis, 030220 oncology & carcinogenesis, KRAS, business
Abstract: We aimed to study the prognostic impact of the mutational landscape in primary and secondary myelofibrosis. The study included 479 patients with myelofibrosis recruited from 24 French Intergroup of Myeloproliferative Neoplasms (FIM) centers. The molecular landscape was studied by high-throughput sequencing of 77 genes. A Bayesian network allowed the identification of genomic groups whose prognostic impact was studied in a multistate model considering transitions from the 3 conditions: myelofibrosis, acute leukemia, and death. Results were validated using an independent, previously published cohort (n = 276). Four genomic groups were identified: patients with TP53 mutation; patients with ≥1 mutation in EZH2, CBL, U2AF1, SRSF2, IDH1, IDH2, NRAS, or KRAS (high-risk group); patients with ASXL1-only mutation (ie, no associated mutation in TP53 or high-risk genes); and other patients. A multistate model found that both TP53 and high-risk groups were associated with leukemic transformation (hazard ratios [HRs] [95% confidence interval], 8.68 [3.32-22.73] and 3.24 [1.58-6.64], respectively) and death from myelofibrosis (HRs, 3.03 [1.66-5.56] and 1.77 [1.18-2.67], respectively). ASXL1-only mutations had no prognostic value that was confirmed in the validation cohort. However, ASXL1 mutations conferred a worse prognosis when associated with a mutation in TP53 or high-risk genes. This study provides a new definition of adverse mutations in myelofibrosis with the addition of TP53, CBL, NRAS, KRAS, and U2AF1 to previously described genes. Furthermore, our results argue that ASXL1 mutations alone cannot be considered detrimental.
Published: 2021
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2. Long-term follow-up of JAK2 exon 12 polycythemia vera: a French Intergroup of Myeloproliferative Neoplasms (FIM) study

Author: Laurane Cottin, Sylvie Tondeur, Jean-Christophe Ianotto, Olivier Mansier, Lenaïg Le Clech, Jean-Marie Chrétien, Franciane Paul, Mélanie Mercier, Laurent Voillat, Dana Ranta, Benoit de Renzis, Olivier Allangba, François Girodon, Christophe Marzac, Mathilde Hunault-Berger, Valérie Ugo, Corentin Orvain, Driss Chaoui, Jérémie Riou, Eric Lippert, Bruno Cassinat, Jean-Jacques Kiladjian, Suzanne Tavitian, Françoise Boyer, Damien Luque Paz, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Biologie et Pathologie [CHU Grenoble] (IBP), CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hématologie Clinique [CHI Cornouaille, Quimper], Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' [Brest] (FHU GOAL), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-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), 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 [CH Argenteuil], CH Argenteuil, Hématologie Clinique [CH Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), 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, 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), Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), UFR Santé [UNIV Angers], Université d'Angers (UA), Laboratoire de Biologie Cellulaire [AP-HP Hôpital Saint-Louis], 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), Cellule de Gestion des Données et Evaluation [CHU Angers] (DRCI - CGDE), Service d'hématologie clinique [CHRU de Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'Hématologie Clinique [CH Saint-Brieuc], Centre hospitalier Saint-Brieuc, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Chalon-sur-Saône William Morey, Service des maladies du sang [Angers], Service d'hématologie [Angers], Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Long term follow up, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cohort Studies, 03 medical and health sciences, Exon, 0302 clinical medicine, Polycythemia vera, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Humans, article clinique, Polycythemia Vera, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Myeloproliferative Disorders, business.industry, Exons, Hematology, Janus Kinase 2, Middle Aged, Prognosis, medicine.disease, Survival Rate, Oncology, Mutation, Female, France, business, Follow-Up Studies, 030215 immunology
Abstract: International audience; No abstract available
Published: 2020
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3. FranceCoag: a 22-year prospective follow-up of the national French cohort of patients with inherited bleeding disorders

Author: Alexandra, Doncarli, Virginie, Demiguel, Irina, Guseva Canu, Véronique, Goulet, Sophie, Bayart, Thierry, Calvez, Sabine, Castet, Vincent, Dalibard, Yohan, Demay, Birgit, Frotscher, Jenny, Goudemand, Thierry, Lambert, Vanessa, Milien, Caroline, Oudot, Thomas, Sannié, Hervé, Chambost, B, Wibaut, Laboratoire d'épidémiologie (IRSN), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Hématogoie pédiatrique, hôpital Sud, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Etudes Fiscales et Financières (CEFF), Aix Marseille Université (AMU), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Association française des hémophiles (AFH), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Santé publique France Guyane, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institute for Work and Health (IST), and Lausanne
Subjects: Adult, Male, Haemophilia, Pediatrics, medicine.medical_specialty, Inhibitor, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Haemophilia A, Population, Coagulation Protein Disorders, 030204 cardiovascular system & hematology, Hemophilia A, Hemophilia B, Young Adult, 03 medical and health sciences, Blood Coagulation Disorders, Inherited, 0302 clinical medicine, Rare inherited disease, medicine, Humans, Haemophilia B, Prospective Studies, 030212 general & internal medicine, Risk factor, Prospective cohort study, education, education.field_of_study, Prophylaxis, business.industry, Middle Aged, medicine.disease, 3. Good health, von Willebrand Diseases, Cohort, Female, France, business, Follow-Up Studies
Abstract: International audience; FranceCoag is an ongoing open prospective multicentre cohort project aimed at improving epidemiological knowledge about inherited bleeding disorders in France. The main objective of this article was to evaluate the project's progress as of the 30th December 2016. Between 1994 and this date, of the 10,047 patients included in the study, 384 (3.8%) were reported by clinicians to have died and 159 (1.6%) to be lost to follow-up. Among the remaining 9504 patients still being followed up, 5748 (60.5%) had haemophilia A, 1300 (13.7%) haemophilia B, 1980 (20.8%) von Willebrand Disease while 476 (5.0%) had another clotting factor deficiency (Factor I, II, V, combined V and VIII, VII, X, XI and XIII). The median age of the population was 32 years (Inter-quartile range (IQR) 18-50 years) at data extraction on December 30th, 2016. The subgroup of children (i.e.
Published: 2018
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4. Effects on Mortality and Cardiovascular Events of Adherence to Guideline-Recommended Therapy 4 Years after Lower Extremity Arterial Revascularization

Author: Martina Thiney, Patrick Feugier, Antoine Millon, Nellie Della Schiava, René Ecochard, Anne Long, Patrick Lermusiaux, Département de chirurgie vasculaire, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Revascularization, Risk Assessment, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Secondary Prevention, medicine, Humans, 030212 general & internal medicine, Practice Patterns, Physicians', ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Anticoagulants, Cardiovascular Agents, General Medicine, Guideline, Protective Factors, Vascular surgery, Confidence interval, Treatment Outcome, Lower Extremity, Practice Guidelines as Topic, Cohort, Arterial revascularization, Drug Therapy, Combination, Surgery, Observational study, Guideline Adherence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Angiotensin II Type 1 Receptor Blockers, Vascular Surgical Procedures, Platelet Aggregation Inhibitors, Cohort study
Abstract: Background All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk of cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events, and additional vascular surgery in vascularized LE-PAD patients. This observational, cohort study analyzed prospectively collected data of 140 consecutive patients after hospitalization for LE-PAD revascularization in the vascular surgery department of our university hospital, between January 1 and June 30, 2013. Methods Data from guideline-recommended classes of medications (ACE, ARB, statins, and antiplatelet agents or anticoagulation) were collected at the time of discharge to hospitalization and at the end of the follow-up. Information about mortality, CV events, and additional vascular surgery was collected during follow-up. Results The mean follow-up of patients was 41 months. Mortality and CV events concerned 24% and 12% of the patients, respectively, and additional vascular surgery was performed in 33% of the patients. There was no difference in mortality and CV event rates according to pharmacologic treatment. Additional vascular surgery rate of LE-PAD patients with best medical treatment tended to be lower than without (incidence rate ratio = 0.5777; 95% confidence interval, 0.3101–1.06; P = 0.08). Best medical treatment was prescribed in 54% of patients at discharge of hospitalization. This proportion (54%) was statistically unchanged at the end of follow-up. Conclusions In this small cohort, we failed to show that best medical treatment decreased mortality or CV event rates, but it tended to be associated with decreased additional vascular surgery rate. Further studies taking into consideration the control of CV risk factors could be interesting to demonstrate better outcome from LE-PAD patients with best medical treatment compared with LE-PAD patients without. There is an urgent need for a more effective implementation of currently recommended medication and a continued search after more effective pharmacologic treatment options in LE-PAD.
Published: 2018
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5. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

Author: Richard Delarue, Emmanuelle Nicolas-Virelizier, Reda Bouabdallah, Veronique Edeline, Bertrand Joly, Adrian Tempescul, Hassan Farhat, Luc-Matthieu Fornecker, Peggy Dartigues, René-Olivier Casasnovas, Laurent Martin, Franck Morschhauser, Aspasia Stamatoullas, Pauline Brice, Marc André, Alain Delmer, Michel Meignan, Nicolas Mounier, Hervé Ghesquières, Jehan Dupuis, Philippe Quittet, Krimo Bouabdallah, Julien Lazarovici, Alina Berriolo-Riedinger, Anne-Claire Gac, Alexandra Traverse-Glehen, Pierre Feugier, Thierry Lamy, Thomas Gastinne, Hervé Maisonneuve, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Henri Mondor, Institut d'Hématologie de Basse-Normandie (IHBN), 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)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Sud Francilien, CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Département de biologie et pathologie médicales [Gustave Roussy], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Nice (CHU Nice), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Dijon, Département d'Hematologie, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CRLCC Henri Becquerel, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie [Nantes], Hôpital Sud-Fancilien, CH Sud-Fancilien, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie Hôpital Mignot, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Lymphocyte B et Auto-immunité (LBAI), 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), CH La Roche-sur-Yon, Service d’Hématologie Clinique [CHU Pontchaillou, Rennes], Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dinant-Godinne UCL Namur, Service de cancérologie, 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), Service de médecine nucléaire [Créteil], Université Grenoble Alpes (UGA), Département Hématologie (FNCLCC), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Régional d'Etudes sur le CANcer (GRECAN), IFR146-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse )-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département d'Hématologie Clinique [CHU Nantes], Université Mohamed Boudiaf de M'sila, Service d’Hématologie Clinique [CHRU Nancy], Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre hospitalier La Roche-Sur-Yon, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologie morphologique, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Pathologie [CHU de Dijon], Service de Médecine Interne Clermont Ferrand (MéDECINE INTERNE - CLERMONT-FERRAND), Hopital, Hôpital Archet 2 [Nice] (CHU), Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CH Evry-Corbeil, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CCSD, Accord Elsevier, Service d'Hématologie Clinique (CHU de Dijon), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’Hématologie [Rouen], CHU Rouen, Service hématologie Créteil, CHU, Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [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), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Département de médecine nucléaire (Institut Curie, Saint-Cloud), Institut Curie [Paris], Hématologie clinique [CH La Roche-sur-Yon], service hématologie Strasbourg, CHU Strasbourg, Service d’Hématologie Clinique [Rennes], Service hématologie Nice, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, CHU Henri Mondor [Créteil], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Male, medicine.medical_specialty, Vincristine, Dacarbazine, [SDV]Life Sciences [q-bio], Salvage therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Procarbazine, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, business.industry, Standard treatment, medicine.disease, Hodgkin Disease, 3. Good health, Vinblastine, Drug Therapy, Computer-Assisted, [SDV] Life Sciences [q-bio], Oncology, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: International audience; Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (
Published: 2019
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6. 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
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7. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

Author: Amandine Baptiste, Thibaud Lefebvre, Olivier Ernst, Emmanuelle Chauzit, Jean-Pierre Vannier, Agnès Guerci-Bresler, Christian Rose, Zoubida Karim, Hervé Puy, Aspasia Stamatoullas, Mariane De Montalembert, Valentine Brousse, Krimo Bouabdallah, Mohamed Touati, C. Dumesnil, Agnès Lahary, Marina Cavazzana, Caroline Elie, Jean-Antoine Ribeil, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre de Référence de la Drépanocytose-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), 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 de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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), CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], 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), Service d'informatique médicale et biostatistiques [CHU Necker], Radiologie interventionnelle, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, Hôpital Saint-Vincent-de-Paul, TAN, Yossan-Var, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence de la Drépanocytose, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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 Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Blood transfusion, Physiology, Thalassemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, 030204 cardiovascular system & hematology, Gastroenterology, Physical Chemistry, Biochemistry, Diagnostic Radiology, 0302 clinical medicine, hemic and lymphatic diseases, Medicine and Health Sciences, Erythropoiesis, 10. No inequality, Child, lcsh:Science, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Chelation, Radiology and Imaging, Heart, Hematology, Middle Aged, Magnetic Resonance Imaging, Sickle cell anemia, Clinical Laboratory Sciences, 3. Good health, [SDV] Life Sciences [q-bio], Chemistry, Genetic Diseases, 030220 oncology & carcinogenesis, Physical Sciences, Female, Anatomy, Research Article, Adult, medicine.medical_specialty, Iron Overload, Adolescent, Anemia, Imaging Techniques, Iron, Anemia, Sickle Cell, Research and Analysis Methods, Iron Chelating Agents, 03 medical and health sciences, Autosomal Recessive Diseases, Hepcidin, Diagnostic Medicine, Internal medicine, medicine, Humans, Blood Transfusion, Clinical Genetics, Ferritin, Sickle Cell Disease, Chemical Bonding, business.industry, Transfusion Medicine, Myelodysplastic syndromes, Myocardium, lcsh:R, Biology and Life Sciences, Proteins, Protein Complexes, medicine.disease, Hematopoiesis, Hemoglobinopathies, Myelodysplastic Syndromes, biology.protein, Cardiovascular Anatomy, lcsh:Q, business, Physiological Processes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P
Published: 2017
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8. Natural killer-cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study

Author: Antoine Toubert, Agnès Guerci-Bresler, Hélène Moins-Teisserenc, Gabriel Etienne, Delphine Rea, Françoise Huguet, Laurence Legros, François Guilhot, Frédéric Maloisel, Zena Khaznadar, Joelle Guilhot, Martine Gardembas, Philippe Rousselot, Francois-Xavier Mahon, Bruno Villemagne, Jean-Christophe Ianotto, Franck E. Nicolini, Nicolas Dulphy, Viviane Dubruille, Aude Charbonnier, Guylaine Henry, Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Institut Bergonié [Bordeaux], UNICANCER, INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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 l'Archet - CHU de Nice, Service des maladies du sang [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'Hématologie Clinique [Hôpital Hôtel Dieu, Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Hôtel Dieu, Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alloimmunité-Autoimmunité-Transplantation (A2T), and Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, medicine.drug_class, Receptor expression, Chronic Myeloid Leukemia, Cell Count, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Tyrosine-kinase inhibitor, Article, Disease-Free Survival, Natural killer cell, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Recurrence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, medicine, Cytotoxic T cell, Humans, Protein Kinase Inhibitors, business.industry, Degranulation, Myeloid leukemia, Imatinib, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, 3. Good health, Killer Cells, Natural, Leukemia, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, Imatinib Mesylate, Receptors, Natural Killer Cell, business, medicine.drug
Abstract: Despite persistence of leukemic stem cells, patients with chronic myeloid leukemia who achieve and maintain deep molecular responses may successfully stop the tyrosine kinase inhibitor imatinib. However, questions remain unanswered regarding the biological basis of molecular relapse after imatinib cessation. In IMMUNOSTIM, we monitored 51 patients from the French Stop IMatinib trial for peripheral blood T cells and natural killer cells. Molecular relapse-free survival at 24 months was 45.1% (95% CI: 31.44%-58.75%). At the time of imatinib discontinuation, non-relapsing patients had significantly higher numbers of natural killer cells of the cytotoxic CD56dim subset than had relapsing patients, while CD56bright natural killer cells, T cells and their subsets did not differ significantly. Furthermore, the CD56dim natural killer-cell count was an independent prognostic factor of molecular-relapse free survival in a multivariate analysis. However, expression of natural killer-cell activating receptors, BCR-ABL1+ leukemia cell line K562-specific degranulation and cytokine-induced interferon-gamma secretion were decreased in non-relapsing and relapsing patients as compared with healthy individuals. After imatinib cessation, the natural killer-cell count increased significantly and stayed higher in non-relapsing patients than in relapsing patients, while receptor expression and functional properties remained unchanged. Altogether, our results suggest that natural killer cells may play a role in controlling leukemia-initiating cells at the origin of relapse after imatinib cessation, provided that these cells are numerous enough to compensate for their functional defects. Further research will decipher mechanisms underlying functional differences between natural killer cells from patients and healthy individuals and evaluate the potential interest of immunostimulatory approaches in tyrosine kinase inhibitor discontinuation strategies. (ClinicalTrial.gov Identifier NCT00478985).
Published: 2017
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9. CD19 CAR T-Cell Therapy in Patients with Relapse/Refractory DLBCL: Retrospective Analysis of the Eligibility Criteria

Author: Driss Chaoui, Vincent Camus, Jean-Pierre Marolleau, Maxime Berquier, Véronique Meignin, Géraldine Salmeron, Bénédicte Deau-Fischer, Rene-Olivier Casasnovas, Luc Mathieu Fornecker, Anne Quinquenel, Celia Salanoubat, Frédérique Kuhnowski, Véronique Morel, Gandhi Damaj, Roberta Di Blasi, Pierre Feugier, Catherine Thieblemont, Sophie Bernard, Elie Azoulay, Michael Darmon, Jérôme Paillassa, Guillaume Cartron, Sophie Rigaudeau, David Sibon, Emmanuel Gyan, Vincent Delwail, Sylvie Chevret, Corinne Haioun, Jean Valère Malfuson, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service de biostatistiques et information médicale [Saint-Louis], 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)-Université Paris Cité (UPCité), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Fondation FondaMental [Créteil], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie, Argenteuil, Centre Hospitalier Victor Dupouy, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie [Institut Curie], Institut Curie [Paris], Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Service clinique des Maladies du Sang, CHU Amiens-Picardie, Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), Service d'Hématologie Clinique [CHU Reims], Hôpital universitaire Robert Debré [Reims], Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Sud Francilien, Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hémato-oncologie [CHU Saint-Louis], 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), and DESSAIVRE, Louise
Subjects: 0301 basic medicine, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Immunology, Primary central nervous system lymphoma, Salvage therapy, Waldenstrom macroglobulinemia, Cell Biology, Hematology, medicine.disease, Biochemistry, [SDV] Life Sciences [q-bio], Clinical trial, Transplantation, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Extrapyramidal disorder, medicine, business, Diffuse large B-cell lymphoma, Progressive disease, 030215 immunology
Abstract: Introduction: The autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells demonstrated significant clinical benefits and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with an ORR of 52-83% and CR of 40-58% in the 3 pivotal clinical trials (ZUMA-1, TRANSCEND-NHL-001, JULIET), leading to a rapid approval in third line R/R DLBCL in Europe and in USA. The CD19 CAR T-cells Axicabtagene and Tisagenlecleucel have been approved in France since June 2018 for patients with DLBCL, primary mediastinal B-cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after > 2 systemic therapy lines. However, all patients are not deemed eligible for such therapy. Here we describe the characteristics of the non-eligible patients and the causes of non-eligibility for CD19 CAR T-cells at our center. Methods: We performed a retrospective analysis of all patients for whom our center was contacted for potential eligibility to CD19 CAR T-cells. Upon each request, a screening form was completed by the referring hospital to validate the indication (DLBCL, PMBL or tFL; recurrent or refractory to > 2 systemic therapy lines) and the absence of contra-indications (CNS involvement (MRI mandatory), active infection). The patient was then evaluated in our hospital to check the predetermined eligibility criteria: age, comorbidities, LVEF > 45%, no pericarditis or cardiogram abnormality, creatinine clearance > 60 mL/min, ALT/AST < 2.5 N, total bilirubin < 1.5 mg/dL, no pleural effusion, SpO2 > 92% without oxygen, lymphocytes > 100/µL, no rapid progressive disease (compressive mass, PS > 2 or rapid increase of LDH), or no active neurological/auto-immune disease. In case of severe comorbidities or age> 70, patient's frailty index was assessed by an ICU physician. Eligibility was then finally validated by our local board through a careful case-by-case analysis. Results: Between June 2018 and July 31, 2019, 221 requests were analyzed. Evaluation is still ongoing for 6 patients (3%). 80/215 patients (37%) were deemed eligible for CAR T-cells, 58 patients (27%) were excluded before any visit at the expert hospital because of histology other than DLBCL, PMBL and tFL (n=30: non-transformed FL 9, transformed SLL/CLL 7, transformed Waldenström 3, transformed MZL 3, MZL 2, primary CNS lymphoma 2, SLL/CLL 1, HL 1, lymphoblastic lymphoma 1, CD19- 1), < 2 previous lines (n=7), CNS involvement (n=7), administrative reason (n=14). The remaining 77 patients (36%) were deemed non-eligible for CAR T-cells after the first visit. Median age was 59 years (range 18-86, 41% ≥ 65 years), 68% were male. There were 62, 4 and 2 patients with DLBCL, PMBL and tFL, respectively. Median number of prior lines was 3 (range 2-11, 43% > 3 lines), 86% of patients presented with a primary refractory disease. Nine patients were with a refractory disease despite stem cell transplantation (SCT, 5 autologous, 3 allogeneic and 1 both). Considering these 77 patients, 12 (16%) had 2 concomitant causes of non-eligibility. Overall, the two main causes of non-eligibility were rapid disease progression (n=49) and major frailty (n=23), including 10 patients with 11 severe organ dysfunctions [5 cardiac, 3 kidney, 1 liver, 1 respiratory and 1 heavy engine handicap]. Replicative viral infections (n=4) constituted also an important cause of frailty: HIV (1), HBV (2), HBV + HCV (1). Two patients had a solid organ transplantation requiring immunosuppressive drugs. Advanced neurological diseases (n=4) included: extrapyramidal syndrome (3), advanced multiple sclerosis (1). Active autoimmune diseases were a cause of frailty for 2 patients: thyroiditis (1), periodic fever (1). In one patient, the screening evaluation showed a concomitant malignancy. Other causes of non-eligibility were found in 17 patients: complete remission after the salvage therapy (n=7), age > 80 (n=4), severe thrombocytopenia < 20 G/L (n=2), no slot available (n=1), patient refusal (n=3). Outcomes of the non-eligible patients (alternative treatments, survival) will be presented at the meeting. Conclusion: In this pioneering experience, 37% of patients in whom a CAR T-cell request is made are ultimately deemed eligible for the therapy. Other patients are either rapidly excluded based on lack of CAR T-cells indications (27%), or deemed non-eligible because of failure to control the disease / major frailty (36%). Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Gyan:Pfizer: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Novartis: Honoraria.
Published: 2019
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10. Molecular Characterisation of Diffuse Large B Cell Lymphoma in Patients of 80 Years Old or More: Clinical Relevance in a Multicentric Randomized Phase III Study of the Lysa (SENIOR Study)

Author: Hervé Tilly, Vinciane Marchand, Corinne Haioun, Pierre-Julien Viailly, Vincent Delwail, Mathieu Viennot, Rene-Olivier Casasnovas, Catherine Thieblemont, Steven Le Gouill, Fabrice Jardin, Pierre Feugier, Gandhi Damaj, Victor Bobée, Hervé Maisonneuve, Peggy Dartigues-Cuillères, Philippe Gaulard, Bettina Fabiani, Jean-François Emile, Elodie Bohers, Gianmatteo Pica, Philippe Ruminy, Frederic Peyrade, Fontanet Bijou, Julie Abraham, Gilles Salles, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d’Onco-Hématologie [La Roche sur Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Hôpital Dupuytren [CHU Limoges], Service d'Hémato-oncologie [CHU Saint-Louis], 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), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Institut Bergonié [Bordeaux], UNICANCER, 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), Service Hématologie [CH Métropole Savoie, Chambery], Centre Hospitalier Métropole Savoie [Chambéry], Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], 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), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Départemental Vendée, Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Bergonié - CRLCC Bordeaux, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), and 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)
Subjects: Neoplasm DNA, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Biopsy, medicine, Clinical significance, In patient, Genotype determination, 030304 developmental biology, Lenalidomide, 0303 health sciences, medicine.diagnostic_test, business.industry, Cell Biology, Hematology, medicine.disease, 3. Good health, business, Diffuse large B-cell lymphoma, Protein p53, 030215 immunology, medicine.drug
Abstract: Introduction The outcome of very elderly patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) remains poorer than that of younger patients, often because of co-morbidities and physiological organ function impairment. However, the biological specificities of DLBCL in very elderly patients are unknown. The LYSA conducted a multicentric, phase III, open-label, randomized trial in newly diagnosed DLBCL > 80y evaluating the efficacy of the combination of lenalidomide with R-miniCHOP (R2-miniCHOP) in comparison to the standard R-miniCHOP (SENIOR trial, NCT02128061). Based on targeted NGS sequencing and gene expression profile (GEP) analysis, the BIOSENIOR project aimed to provide a molecular characterisation of the cohort and detect clinically relevant biomarkers in according to treatment arm. Methods The SENIOR study enrolled patients aged of 80 years or more with non-previously treated CD20+ DLBCL, age-adjusted IPI= 0 to 3, and Ann Arbor stage II to IV. 249 patients were randomized (127 in R-miniCHOP arm and 122 in R2-miniCHOP arm). Median age was 83y (range 80-96. Patients with available tumor DNA /RNA from FFPE biopsies were included in the BIOSENIOR substudy. GEP was performed using Lymph2CX assay (Nanostring®) and a new RTMLPA assay (Bobée et al. J Mol Diagn 2017) able to quantify the expression of 137 relevant genes involved in B-cell biology, microenvironment or therapeutic response (cereblon). Genotyping (QiaSeq ®) was performed using a dedicated 36 genes panel. GEP features were compared to DLBCL patients < 60y enrolled in the LYSA GAINED trial (NCT01659099). Results Tumor DNA/RNA was available for 164/249 patients (66%). GEP was performed in 154 cases by RTMLPA and in 103 cases by Lymph2CX. The concordance to classify GCB/ABC was of 94% between the two technologies. DLBCL were mainly classified in the ABC subtype [77 = ABC (50%); 53 = GCB (34.4%); 17 unclassified (11%)]. Four cases (2.6%) were classified as EBV+ DLBCL and 1 as PMBL. 81 cases (52.5%) were considered as BCL2+, 23 (15%) as MYC+ and 16 (10.4%) as double-expressors (DE) by GEP. Comparison of GEP with younger patients highlighted distinct features and geriatric specificities (figure 1A). Genotypes were obtained in 159 patients. MYD88, PIM1, CREBBP, CD79B and TP53 were the five most frequently mutated genes (Figure 1B). Correlations between biomarkers and outcomes (OS and PFS) were performed in the overall population and according to treatment arms. The GCB/ABC subtyping, as determined by Lymph2CX (n = 97) was related to OS [HR = 0.38 (0.18 - 0.81) Log-rank: 0.009] and PFS in the overall population. This result was not confirmed in the extended cohort (n = 154) by RTMLPA. The MYC / BCL2 DE status assessed by GEP was a strong predictor of outcome (OS, HR = 2.89 (1.39 - 5.97) Log-rank: 0.003] in both arms. Importantly MYC/BCL2 DE was independent of the IPI score and albuminemia in multivariate analysis. In an exploratory analysis, cereblon (HR = 2.360; CI-95% 1.157-4.812, Log-rank: 0.015) and PD1 [HR = 0.33 (0.16 - 0.66) Log-rank: 0.001] expressions correlate exclusively with PFS in the R2-miniCHOP arm. MYD88 mutations (L265P and others variants) were associated with a worse outcome in the overall population (OS, HR= 2.05, CI-95% 1.190-3.554, Log-rank: 0.008; PFS, HR =1.731, CI-95% 1.059-2.830 Log-rank: 0.027). FOXO1 mutations were detected in 15 patients (9%). Its impact was only observed in the R-miniCHOP arm (OS, HR = 4.07 (1.52 - 10.87) Log-rank: 0.0024; PFS HR = 4.139 (1.59 - 10.79) Log-rank: 0.0016)] and was erased in the R2-miniCHOP arm. TP53 mutations, reported in 24% of cases were predictive of the PFS in the overall population [HR = 1.811 (1.09 - 3.01) Log-rank: 0.0199](prognostic factors are summarized in Table 1). Conclusion BIOSENIOR is an ancillary study of the first prospective phase III trial in ³80 years old patients with newly diagnosed DLBCL. Some biomarkers, known to be predictive in younger patients, are relevant in this cohort, including MYC expression, BCL2/MYC DE, mutations of MYD88, TP53 or FOXO1. However, GEP characteristics of DLBCL occurring in this very old population are highly different of younger patients, suggesting distinct underlying oncogenic mechanisms. BIOSENIOR indicates that, beyond geriatric frailty, molecular features of DLBCL patients > 80y play also a crucial role that should be considered in the design of future trials. Markers that may predict R2-miniCHOP efficacy remain to be confirmed. Disclosures Thieblemont: Janssen: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Roche: Honoraria, Research Funding; Cellectis: Membership on an entity's Board of Directors or advisory committees. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Salles:Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria. Tilly:Roche: Consultancy; Celgene: Consultancy, Research Funding; Astra-Zeneca: Consultancy; Karyopharm: Consultancy; BMS: Honoraria; Janssen: Honoraria; Gilead: Honoraria; merck: Honoraria; servier: Honoraria; roche: Membership on an entity's Board of Directors or advisory committees. Haioun:celgene: Honoraria; novartis: Honoraria; servier: Honoraria; amgen: Honoraria; janssen cilag: Consultancy; takeda: Consultancy; gilead: Consultancy; celgene: Consultancy; roche: Consultancy. Le Gouill:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche-Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jardin:janssen: Honoraria; roche: Honoraria; amgen: Honoraria; celgene: Honoraria; Servier: Honoraria. OffLabel Disclosure: lenalidomide is evaluatd in combination with RminiHOP
Published: 2019
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11. Myelodysplastic syndromes with single neutropenia or thrombocytopenia are rarely refractory cytopenias with unilineage dysplasia by World Health Organization 2008 criteria and have favourable prognosis

Author: Beyne-Rauzy, Odile, Sebert, Marie, Sapena, Rosa, Zerazhi, Hacène, Legros, Laurence, Guerci-Bresler, Agnès, Ame, Shanti Natarjan, Germing, Ulrich, Santini, Valeria, Salvi, Flavia, Gioia, Daniela, Lunghi, Monia, Dreyfus, François, Fenaux, Pierre, Sindromi, Fdn Italiana, Registry, Dusseldorf Mds, Gyan, Emmanuel, Andrieu, Valerie, Sanna, Alessandro, Caille, Agnès, Schemenau, Jennifer, Sudaka, Isabelle, Siguret, Virginie, Malet, Michele, Park, Sophie, Bordessoule, Dominique, Mairesse, Jacques, Gelsi-Boyer, Véronique, Cheze, Stephane, Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Haematology, Oncology and Clinical Immunology, Centre for Haematology and Oncology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Service d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémopathies Myéloïdes : Cellules Souches, Modèles Pré-Cliniques et Recherche Translationnelle (UMR 1131), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d’Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Thrombose : Épidémiologie, Physiopathologie et Thérapeutiques Innovantes (UMR_S 765), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, 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), Centre de Recherche en Économie et Statistique (CREST), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE Paris)-Centre National de la Recherche Scientifique (CNRS), 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), Service de Médecine Interne et Immunopathologie, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hémopathies Myéloïdes : Cellules Souches, Modèles Pré-Cliniques et Recherche Translationnelle, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], IUH- Institut Universitaire d'hématologie, Université Paris Diderot - Paris 7 ( UPD7 ), CHRU Tours, CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CIC 1415, Institut National de la Santé et de la Recherche Médicale-Université Francois Rabelais [Tours], Thrombose : Épidémiologie, Physiopathologie et Thérapeutiques Innovantes ( UMR_S 765 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Cochin [AP-HP], 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 ), Centre de Recherche en Économie et Statistique ( CREST ), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] ( ENSAI ) -École polytechnique ( X ) -École Nationale de la Statistique et de l'Administration Économique ( ENSAE ParisTech ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Francois Rabelais [Tours], Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE ParisTech )-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)-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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pediatrics, medicine.medical_specialty, classifications, diagnostic haematology, MDS, neutropenia, thrombocytopenia, Hematology, business.industry, Myelodysplastic syndromes, Neutropenia, medicine.disease, World health, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 03 medical and health sciences, 0302 clinical medicine, Refractory, Dysplasia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030220 oncology & carcinogenesis, Immunology, medicine, Young adult, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: International audience; no abstract
Published: 2016
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12. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study

Author: Bruno Villemagne, Martine Escoffre-Barbe, Michel Tulliez, Valérie Coiteux, Francois-Xavier Mahon, Gaelle Guillerm, Marie-Pierre Noel, Laurence Legros, François Guilhot, Joelle Guilhot, Franck E. Nicolini, Martine Gardembas, Jean-Christophe Ianotto, Philippe Rousselot, Agnès Guerci-Bresler, Hyacinthe Johnson-Ansah, Jean-Michel Pignon, Aude Charbonnier, Gabriel Etienne, Delphine Rea, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), 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), INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire d'hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Pontchaillou [Rennes], CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), 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, Pathologie et virologie moléculaire (PVM (UMR_7151)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Dasatinib, Fusion Proteins, bcr-abl, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, RNA, Messenger, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Univariate analysis, business.industry, Incidence, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Middle Aged, medicine.disease, Interim analysis, Confidence interval, 3. Good health, Surgery, Discontinuation, Leukemia, Pyrimidines, Treatment Outcome, Nilotinib, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: STOP second generation (2G)-tyrosine kinase inhibitor (TKI) is a multicenter observational study designed to evaluate 2G-TKI discontinuation in chronic myeloid leukemia (CML). Patients receiving first-line or subsequent dasatinib or nilotinib who stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the 2 preceding years at least were eligible for inclusion. This interim analysis reports outcomes of 60 patients with a minimum follow-up of 12 months (median 47, range: 12-65). Twenty-six patients (43.3%) experienced a molecular relapse defined as the loss of a major molecular response (MMR). Relapses occurred after a median time of 4 months (range: 1-38). Cumulative incidences of molecular relapse by 12 and 48 months were 35% (95% confidence interval [CI], 24.79% to 49.41%) and 44.76% (95% CI, 33.35% to 59.91%), respectively. Treatment-free remission (TFR) rates at 12 and 48 months were 63.33% (95% CI, 51.14% to 75.53%) and 53.57% (95% CI, 40.49% to 66.65%), respectively. In univariate analysis, prior suboptimal response or TKI resistance was the only baseline factor associated with significantly worse outcome. A landmark analysis demonstrated that loss of MR4.5 3 months after stopping TKI was predictive of failure to maintain MMR later on. During the treatment-free phase, no progression toward advanced phase CML occurred, and all relapsing patients regained MMR and MR4.5 after restarting therapy. In conclusion, discontinuation of first-line or subsequent 2G-TKI yields promising TFR rates without safety concerns. Further research is encouraged to better define conditions that will offer patients the highest chance to remain free from 2G-TKI therapy.
Published: 2016
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13. How Admission to a Vascular Surgery Department Improves Medical Treatment in Patients with Lower Extremity Peripheral Arterial Disease

Author: Patrick Feugier, Anne Long, Antoine Millon, Nellie Della Schiava, Martina Thiney, Patrick Lermusiaux, Jacques Ninet, Département de chirurgie vasculaire, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Service de Médecine Interne, Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Severity of Illness Index, Coronary artery disease, Hospitals, University, 0302 clinical medicine, Drug Utilization Review, Patient Admission, 030212 general & internal medicine, Practice Patterns, Physicians', ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, General Medicine, Middle Aged, Quality Improvement, Patient Discharge, Peripheral, Treatment Outcome, Lower Extremity, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, medicine.drug, Specialization, medicine.medical_specialty, Statin, medicine.drug_class, Revascularization, Drug Prescriptions, 03 medical and health sciences, Peripheral Arterial Disease, Internal medicine, medicine, Humans, Medical prescription, Aged, Quality Indicators, Health Care, Retrospective Studies, Cardiovascular History, business.industry, Cardiovascular Agents, Vascular surgery, medicine.disease, Surgery, ACE inhibitor, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Angiotensin II Type 1 Receptor Blockers, Delivery of Health Care, Surgery Department, Hospital, Platelet Aggregation Inhibitors
Abstract: Background All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs), and hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the number of patients who received best medical treatment at admission and at discharge from a vascular surgery department. We also examined the number of patients who received adapted medical treatment and every pharmacologic class separately. Finally, we investigated whether there were differences in prescribing rates according to patient characteristics and cardiovascular history, clinical grade of LE-PAD, and the type of surgery practiced. Materials and Methods This study is a retrospective chart analysis of 140 consecutive patients admitted to the vascular surgery department of our university hospital, between January 1, 2013, and June 30, 2013. To be included, patients required a vascular surgery for peripheral arterial disease with atherosclerosis. Data from guideline-recommended classes of medications (antiplatelet agents, ACE, ARBs, and statins) at the time of admission and discharge were collected and compared. Results Best medical treatment was prescribed in 44% patients before hospital admission and in 50% at discharge ( P = 0.10). Before hospital admission, 84% of patients had antiplatelet therapy compared with 96% at discharge ( P = 0.0004); 73% had a statin, compared with 83% at discharge ( P = 0.001); 64% had an ACE inhibitor or ARB, compared with 63% at the time of discharge ( P = 1).The proportion of patients receiving best medical treatment at admission and discharge increased in case of coronary artery disease ( P = 0.004). There was no difference in prescriptions of best medical treatment and best or adapted treatments at admission and discharge according to the severity of LE-PAD or type of revascularization. Conclusions Admission to a vascular department significantly increased the rate of prescription of antiplatelet and statin therapy, but no significant improvement was achieved for the prescription of best medical treatment and best or adapted treatments.
Published: 2016
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14. Response to rituximab in B-CLL patients is adversely impacted by frequency of IL-10 competent B cells and FcγRIIIa polymorphism. A study of FCGCLL/WM and GOELAMS groups

Author: Anne-Laure Gagez, Hervé Maisonneuve, Caroline Dartigeas, Emmanuelle Ferrant, Émilie Tuaillon, Patrick Feugier, Renaud Cezar, Stéphane Leprêtre, Rémi Letestu, Béatrice Mahé, Karine Bollore, Valérie Gouilleux-Gruart, Thérèse Aurran, Guillaume Cartron, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Département de Bactériologie-Virologie et Département d'Information Médicale, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d’Hématologie Clinique [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département d’Hématologie Clinique [CHRU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie biologique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Onco-hématologie [La Roche sur Yon], Centre Hospitalier Universitaire de Nantes, 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), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d’Hématologie Clinique [CHRU Montpellier], Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 03 medical and health sciences, chemistry.chemical_compound, immune system diseases, Obinutuzumab, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Antibody-dependent cell-mediated cytotoxicity, B-Lymphocytes, Polymorphism, Genetic, Hematology, biology, Receptors, IgG, Antibody-Dependent Cell Cytotoxicity, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Interleukin-10, 3. Good health, Lymphoma, Leukemia, Interleukin 10, Treatment Outcome, 030104 developmental biology, Oncology, chemistry, Immunology, biology.protein, Female, Rituximab, Antibody, medicine.drug
Abstract: Rituximab (MabThera, Rituxan) in vivo mechanisms of action remain incompletely understood and could differ depending on the subtype of B-lymphoproliferative disorders. Rituximab has been shown to induce apoptosis, complement-mediated lysis, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADPC) in vitro and there is some evidence pointing towards an involvement of these mechanisms in vivo. Factors affecting rituximab response have been previously described including histology, tumor burden and rituximab pharmacokinetics.1 We previously observed that FcγRIIIa-158 V/F polymorphism also impacts on clinical response. Because this polymorphism affects human IgG1 affinity for FcγRIIIa expressed on both natural killer cells and macrophages, we postulated that ADCC was an important mechanism of rituximab activity in follicular lymphoma.2 New anti-CD20 antibodies, with higher affinity for FcγRIIIa and ADCC such as obinutuzumab, have been therefore developed and are currently in clinical development.
Published: 2016
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15. Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B-cell neoplasms

Author: M. De Carvalho Bittencourt, Véronique Latger-Cannard, Jean-François Lesesve, S. Tardy, B. Frotscher, Pierre Feugier, Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Immunologie [CHRU Nancy], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: Pathology, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, Clinical Biochemistry, Mature B-Cell, Gene Expression, Lymphoma, Mantle-Cell, 0302 clinical medicine, Immunophenotyping, hemic and lymphatic diseases, Receptors, Immunologic, Lymphoma, Follicular, Characteristic morphology, Aged, 80 and over, 0303 health sciences, B-Lymphocytes, Leukemia, Hairy Cell, medicine.diagnostic_test, Hematology, General Medicine, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Adult, medicine.medical_specialty, B-cell neoplasms, Lymphocytosis, GPI-Linked Proteins, Flow cytometry, Diagnosis, Differential, 03 medical and health sciences, immunophenotyping, Antigens, CD, Predictive Value of Tests, medicine, Biomarkers, Tumor, Humans, 030304 developmental biology, Aged, business.industry, Biochemistry (medical), Cytogenetics, Gold standard (test), Lymphoma, B-Cell, Marginal Zone, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, ROC Curve, CD200, Case-Control Studies, Differential diagnosis, CD160, business, CLL
Abstract: SummaryIntroduction Chronic lymphocytic leukemia is usually diagnosed through the characteristic morphology/immunophenotype of the lymphocytes, but some CLL cases remain atypical resulting in diagnostic uncertainty. Methods Using flow cytometry analysis, we investigated the expression of CDs160/200 on B cells from 124 patients (82 CLL, 42 other B-cell neoplasms) and nine controls. CDs160/200 measurements were determined as a ratio of the mean fluorescence intensities of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively. Results Sixty and 83% CLL expressed CDs160/200 as compared to 5% and 10% of other B-cell neoplasms, respectively. None of the controls showed CDs160/200 expressions. Combination of both markers was observed in 55% of CLL but only in 2% of other B-cell neoplasms, and absence of both markers occurred in 12% of CLL but in 86% of other B-cell neoplasms. Conclusion CDs160/200 were associated with markers of the gold standard ‘Matutes score’ and could be useful markers to differentiate atypical CLL from other B-cell neoplasms in the absence of available biopsies or cytogenetics and molecular studies.
Published: 2014
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16. Efficacy and safety profile of long-term exposure to lenalidomide in patients with recurrent multiple myeloma

Author: Fouquet, Guillemette, Tardy, Stéphanie, Demarquette, Helene, Bonnet, Sarah, Gay, Julie, Debarri, Houria, Herbaux, Charles, Guidez, Stephanie, Michel, Jessica, Perrot, Aurore, Serrier, Caroline, Miljkovic, Darko, Avet Loiseau, Hervé, Facon, Thierry, Hulin, Cyrille, Leleu, Xavier, Service d'Hématologie [CHU Huriez Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Celgene, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], UL, NGERE, 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], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; BACKGROUNDLenalidomide in combination with dexamethasone (Len/Dex) is indicated for patients with recurrent/refractory multiple myeloma (RRMM) who were treated with 1 prior therapy until evidence of disease progression. The objective of the current study was to determine the efficacy and safety profile of long-term exposure to Len/Dex.METHODSA total of 50 patients with RRMM who were treated with long-term Len for ≥ 2 years from 2 Intergroupe Francophone du Myélome (IFM) centers (Lille and Nancy) were included in the current study.RESULTSThe median age of the patients was 58 years, with 30% of the patients aged > 65 years, 49% having an International Staging System stage of 2 and 3, 12% having severe renal insufficiency, and 8% demonstrating an adverse result on fluorescence in situ hybridization. Approximately 56% of the patients received treatment with Len/Dex for ≥ 3 years. The median duration of treatment with Len/Dex was 3 years (range, 2 years-7 years). The response rates for partial response or better and very good partial response or better for the overall cohort were 96% and 74%, respectively, which is similar to patients exposed to Len for ≥ 3 years. With a median follow-up of 4 years, 19 (38%) patients had stopped treatment with Len/Dex. The time to disease progression rate at 37 months was 78% and 91%, respectively, in patients exposed to Len for 2 years to
Published: 2013
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17. Sideroblastic anemia: molecular analysis of ALAS2 gene in a series of 29 probands and functional studies of ten missense mutations

Author: Ducamp, Sarah, Kannengiesser, Caroline, Touati, Mohamed, Garçon, Loïc, Guerci-Bresler, Agnès, Guichard, Jean-François, Vermylen, Christiane, Dochir, Joaquim, Poirel, Hélène Antoine, Fouyssac, Fanny, Mansuy, Ludovic, Leroux, Geneviève, Tertian, Gérard, Girot, Robert, Heimpel, Hermann, Matthes, Thomas, Talbi, Neila, Deybach, Jean-Charles, Beaumont, Carole, Puy, Hervé, Grandchamp, Bernard, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Français des Porphyries, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), genetics, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service d'Hématologie biologique [CHU Limoges], CHU Limoges, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Médecine Interne-Pathologie Vasculaire - Immunologie Clinique, Hôpital Sainte Blandine, Génétique Hématologique, Clinique Universitaire Saint-Luc, de Duve Institute, UCL, Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medizinische Universitätsklinik III, and Hôpitaux Universitaires de Genève (HUG)
Subjects: Life Sciences
Abstract: International audience; X-linked Sideroblastic Anemia (XLSA) is the most common genetic form of sideroblastic anemia, a heterogeneous group of disorders characterized by iron deposits in the mitochondria of erythroid precursors. XLSA is due to mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. Thirteen different ALAS2 mutations were identified in 16 out of 29 probands with sideroblastic anemia. One third of the patients were females with a highly skewed X-chromosome inactivation. The identification of seven novel mutations in the ALAS2 gene, six missense mutations, and one deletion in the proximal promoter extends the allelic heterogeneity of XSLA. Most of the missense mutations were predicted to be deleterious and ten of them, without any published functional characterization, were expressed in E. coli. ALAS2 activities were assayed in vitro. Five missense mutations resulted in decreased enzymatic activity under standard conditions, and two other mutated proteins had decreased activity when assayed in the absence of exogenous pyridoxal phosphate and increased thermosensitivity. Although most amino-acid substitutions result in a clearly decreased enzymatic activity in vitro, a few mutations have a more subtle effect on the protein that is only revealed by in vitro tests under specific conditions.
Published: 2011
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18. Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome.

Author: Berger MG, Pereira B, Rousselot P, Cony-Makhoul P, Gardembas M, Legros L, Escoffre-Barbe M, Nicolini FE, Saugues S, Lambert C, Réa D, Guerci-Bresler A, Giraudier S, Guilhot J, Saussele S, and Mahon FX
Subjects: Aged, Duration of Therapy, Female, Humans, Male, Middle Aged, Risk Factors, Time Factors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Osteoarthritis chemically induced, Osteoarthritis epidemiology, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects
Abstract: The effectiveness of tyrosine kinase inhibitors (TKIs) has made it possible to consider treatment discontinuation in chronic myeloid leukaemia (CML) patients that achieve an excellent response. However, a few of the patients included in the Europe Stop Tyrosine Kinase Inhibitors (EURO-SKI) trial reported musculoskeletal pain shortly after stopping TKIs, considered as a withdrawal syndrome (WS). To identify factors that may predispose to TKI WS, we analysed the pharmacovigilance declarations for the 6 months after stopping TKIs in a large cohort of CML (n = 427) that combined the French patients included in the STop IMatinib 2 (STIM2; n = 224) and EURO-SKI (n = 203) trials. Among these patients, 23% (99/427) developed TKI WS after stopping imatinib (77/373; 20·4%), nilotinib (12/29; 41·4%) or dasatinib (10/25; 40%). WS concerned mainly the upper body joints, and required multiple symptomatic treatments in 30% of patients. Univariate and multivariate analyses identified two risk factors: duration of TKI treatment [risk ratio (RR) = 1·68 (1·02-2·74)] with a 93-month cut-off time, and history of osteoarticular symptoms [RR = 1·84 (1·04-3·28)]. These findings confirm that WS is a TKI class effect. CML patients should be carefully screened before treatment initiation to identify pre-existent osteoarticular symptoms. Moreover, before TKI discontinuation, patients should be informed of the possibility of WS, particularly after a long treatment period., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)
Published: 2019
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18 results on '"Service d'Hématologie Clinique [CHRU Nancy]"'

1. Genomic analysis of primary and secondary myelofibrosis redefines the prognostic impact of ASXL1 mutations: a FIM study

2. Long-term follow-up of JAK2 exon 12 polycythemia vera: a French Intergroup of Myeloproliferative Neoplasms (FIM) study

3. FranceCoag: a 22-year prospective follow-up of the national French cohort of patients with inherited bleeding disorders

4. Effects on Mortality and Cardiovascular Events of Adherence to Guideline-Recommended Therapy 4 Years after Lower Extremity Arterial Revascularization

5. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

6. 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

7. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

8. Natural killer-cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study

9. CD19 CAR T-Cell Therapy in Patients with Relapse/Refractory DLBCL: Retrospective Analysis of the Eligibility Criteria

10. Molecular Characterisation of Diffuse Large B Cell Lymphoma in Patients of 80 Years Old or More: Clinical Relevance in a Multicentric Randomized Phase III Study of the Lysa (SENIOR Study)

11. Myelodysplastic syndromes with single neutropenia or thrombocytopenia are rarely refractory cytopenias with unilineage dysplasia by World Health Organization 2008 criteria and have favourable prognosis

12. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study

13. How Admission to a Vascular Surgery Department Improves Medical Treatment in Patients with Lower Extremity Peripheral Arterial Disease

14. Response to rituximab in B-CLL patients is adversely impacted by frequency of IL-10 competent B cells and FcγRIIIa polymorphism. A study of FCGCLL/WM and GOELAMS groups

15. Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B-cell neoplasms

16. Efficacy and safety profile of long-term exposure to lenalidomide in patients with recurrent multiple myeloma

17. Sideroblastic anemia: molecular analysis of ALAS2 gene in a series of 29 probands and functional studies of ten missense mutations

18. Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome.

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