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1. UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

Author: Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli‑Lebras, Lionel Adès, Delphine Lebon, Céline Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Récher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'hématologie adulte [Hôpital de Saint Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Haut-Lévêque, and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Cancer Research, Oncology, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults.
Published: 2023
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2. Mutations of the integrin αIIb/β3 intracytoplasmic salt bridge cause macrothrombocytopenia and enlarged platelet α-granules

Author: Paquita Nurden, Philippe Rameau, Xavier Pillois, Vasiliki Gkalea, Najet Debili, Marie-Christine Alessi, Marie Favier, Hana Raslova, Jean-Claude Bordet, Alan T. Nurden, Rémi Favier, Nutrition, obésité et risque thrombotique ( NORT ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hémostase, Inflammation et sepsis, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-VetAgro Sup ( VAS ), Hématopoïèse normale et pathologique ( U1170 Inserm ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Haut-Lévêque, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Plateforme imagerie et cytométrie ( PFIC ), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse ( AMMICa ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Gironde, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, Inflammation et sepsis (EA 4609), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Plateforme imagerie et cytométrie (PFIC), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Goletto, Marie-Hélène, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Fibrinolyse et Pathologie Vasculaire, and Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Blood Platelets, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Platelet Aggregation, Integrin, Integrin alpha2, integrin a2IIbb3, Platelet Glycoprotein GPIIb-IIIa Complex, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Cytoplasmic Granules, medicine.disease_cause, inherited macrothrombocytopenia, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Computer Simulation, Family, Platelet, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Gene, enlarged α-granules, ComputingMilieux_MISCELLANEOUS, Genetics, Mutation, Integrin beta3, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Thrombocytopenia, Molecular biology, Phenotype, platelet function defects, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Article RECHERCHE, biology.protein, Salt bridge, Megakaryocytes, 030215 immunology
Abstract: International audience; Rare gain‐of‐function mutations within the ITGA2B or ITGB3 genes have been recognized to cause macrothrombocytopenia (MTP). Here we report three new families with autosomal dominant (AD) MTP, two harboring the same mutation of ITGA2B, αIIbR995W, and a third family with an ITGB3 mutation, β3D723H. In silico analysis shows how the two mutated amino acids directly modify the salt bridge linking the intra‐cytoplasmic part of αIIb to β3 of the integrin αIIbβ3. For all affected patients, the bleeding syndrome and MTP was mild to moderate. Platelet aggregation tended to be reduced but not absent. Electron microscopy associated with a morphometric analysis revealed large round platelets; a feature being the presence of abnormal large α‐granules with some giant forms showing signs of fusion. Analysis of the maturation and development of megakaryocytes reveal no defect in their early maturation but abnormal proplatelet formation was observed with increased size of the tips. Interestingly, this study revealed that in addition to the classical phenotype of patients with αIIbβ3 intracytoplasmic mutations there is an abnormal maturation of α‐granules. It is now necessary to determine if this feature is a characteristic of all mutations disturbing the αIIb R995/β3 D723 salt bridge.
Published: 2017
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3. Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group

Author: Norbert Vey, Claude Preudhomme, Marie Balsat, Christine Terré, Jean-Pierre Marolleau, Thorsten Braun, Sandrine Hayette, Xavier Thomas, Emmanuel Raffoux, Céline Rodriguez, Olivier Nibourel, Céline Berthon, Karine Celli-Lebras, Arnaud Pigneux, Hervé Dombret, Marie Magdeleine Coudé, Aline Renneville, Alice Marceau, Emilie Lemasle, Jean-Michel Cayuela, Denis Caillot, Nicolas Boissel, Stéphane de Botton, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], ERAMET RESEARCH, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), 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 d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), and Hopital Saint-Louis [AP-HP] (AP-HP)
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Neoplasm, Residual, Myeloid, [SDV]Life Sciences [q-bio], Context (language use), 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Cumulative incidence, Acute leukemia, business.industry, Remission Induction, Nuclear Proteins, Myeloid leukemia, Middle Aged, Prognosis, medicine.disease, Minimal residual disease, body regions, Transplantation, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Multivariate Analysis, Mutation, Immunology, Female, business, Nucleophosmin, Stem Cell Transplantation, 030215 immunology
Abstract: Purpose This study assessed the prognostic impact of postinduction NPM1-mutated ( NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P < .001) and a shorter overall survival (OS; hazard ratio [HR], 10.99; P < .001). In multivariable analysis, an abnormal karyotype, the presence of FLT3-internal tandem duplication (ITD), and a < 4-log reduction in PB-MRD were significantly associated with a higher relapse incidence and shorter OS. In the subset of patients with FLT3-ITD, only age, white blood cell count, and < 4-log reduction in PB-MRD, but not FLT3-ITD allelic ratio, remained of significant prognostic value. In these patients with nonfavorable AML according to European LeukemiaNet, disease-free survival and OS were significantly improved by ASCT in those with a < 4-log reduction in PB-MRD. This benefit was not observed in those with a > 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response ( P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1m PB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication.
Published: 2017
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4. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

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

Author: Anna Lam, Frederic Sacher, Jatin Relan, Masateru Takigawa, Mathilde Merle, Ghassen Cheniti, Takeshi Kitamura, Arnaud Denis, Nicolas Derval, Julie Magat, Michael Wolf, Xavier Pillois, Nathaniel Thompson, Mélèze Hocini, Steven Kim, Nicolas Klotz, Jérôme Naulin, Antonio Frontera, Claire A. Martin, Thomas Pambrun, Josselin Duchateau, Felix Bourier, Michel Haïssaguerre, Ruairidh Martin, Florent Collot, Pierre Jaïs, Hubert Cochet, Grégoire Massoullié, Bruno Quesson, Konstantinos Vlachos, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], CHU Bordeaux [Bordeaux], Abbott, Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-EQPX-0030,MUSIC,Plateforme multi-modale d'exploration en cardiologie(2011), ANR-10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), CCSD, Accord Elsevier, Equipements d'excellence - Plateforme multi-modale d'exploration en cardiologie - - MUSIC2011 - ANR-11-EQPX-0030 - EQPX - VALID, Instituts Hospitalo-Universitaires - L'Institut de Rythmologie et modélisation Cardiaque - - LIRYC2010 - ANR-10-IAHU-0004 - IAHU - VALID, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Epicardial Mapping, Percentile, [SDV]Life Sciences [q-bio], Myocardial Infarction, Near and far field, multipolar catheters, 030204 cardiovascular system & hematology, Cardiac Catheters, high-density mapping, 03 medical and health sciences, Cicatrix, Electrocardiography, 0302 clinical medicine, Nuclear magnetic resonance, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Electrode pair, electrograms, Medicine, Animals, 030212 general & internal medicine, LAVA, Electrodes, Sheep, business.industry, Heart, Equipment Design, Magnetic Resonance Imaging, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], Disease Models, Animal, Electrode, Female, business
Abstract: International audience; OBJECTIVESThis study sought to evaluate the relation between bipolar electrode spacing and far- and near-fieldelectrograms.BACKGROUNDThe detailed effects of bipolar spacing on electrograms (EGMs) is not well described.METHODSWith a HD-Grid catheter, EGMs from different bipole pairs could be created in each acquisition. This studyanalyzed the effect of bipolar spacing on EGMs in 7 infarcted sheep. A segment was defined as a 2-mm center-to-centerbipole. In total, 4,768 segments (2,020 healthy, 1,542 scar, and 1,206 in border areas, as defined by magnetic resonanceimaging [MRI]) were covered with an electrode pair of spacing of 2 mm (Bi-2), 4 mm (Bi-4), and 8 mm (Bi-8).RESULTSA total of 3,591 segments in Bi-2 were free from local abnormal ventricular activities (LAVAs); 1,630 segmentswere within the MRI-defined scar and/or border area. Among them, 172 (10.6%) segments in Bi-4 and 219 (13.4%)segments in Bi-8 showed LAVAs. In contrast, LAVAs were identified in 1,177 segments in Bi-2; 1,118 segments were withinthe MRI-defined scar and/or border area. Among them, LAVAs were missed in 161 (14.4%) segments in Bi-4 and in 409(36.6%) segments in Bi-8. In segments with LAVAs, median far-field voltage increased from 0.09 mV (25th to 75thpercentile: 0.06 to 0.14 mV) in Bi-2, to 0.16 mV (25th to 75th percentile: 0.10 to 0.24 mV) in Bi-4, and to 0.28 mV (25thto 75th percentile: 0.20 to 0.42 mV) in Bi-8 (p
Published: 2018
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6. Anti-α IIb β 3 immunization in Glanzmann thrombasthenia: review of literature and treatment recommendations

Author: Roseline d'Oiron, Marie-Christine Alessi, Mathieu Fiore, Xavier Pillois, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hematology, 3Centre de Traitement pour Hémophiles, AP-HP Hôpital Bicêtre, Université Paris XI, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Boullé, Christelle
Subjects: biology, business.industry, Hematology, Human leukocyte antigen, 030204 cardiovascular system & hematology, Platelet membrane glycoprotein, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Platelet transfusion refractoriness, 03 medical and health sciences, 0302 clinical medicine, Platelet transfusion, Immunization, Antigen, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Article RECHERCHE, Immunology, biology.protein, Medicine, Platelet, Antibody, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: Glanzmann thrombasthenia (GT) is caused by inherited defects of the αIIb β3 platelet glycoprotein. This bleeding disorder can be treated with platelet transfusion therapy, but some patients will be immunized and begin to form anti-human leucocyte antigen (HLA) and/or anti-αIIb β3 antibodies. These antibodies can bind and interfere with the function of the transfused platelets, rendering treatment ineffective. However, platelet transfusion refractoriness attributable to HLA antibodies may be managed by the selection of compatible donors, although they are not always readily available, particularly in an emergency. Thus, anti-αIIb β3 antibodies represent one of the most severe complications in GT. Both genetic and environmental factors may contribute to the risk of anti-αIIb β3 development, but the underlying pathogenic mechanisms are still unknown. This review will summarize the current knowledge of the risk factors for development of anti-αIIb β3 antibodies in patients with GT and discuss how these findings may influence the clinical management of patients.
Published: 2018
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7. Cardiac Rhythm Disturbances in Hemodialysis Patients

Author: Sébastien Buffler, Yahsou Delmas, Michel Haïssaguerre, Christian Combe, Cécile Vigneau, Nicolas Klotz, Antoine Bénard, Valerie De Precigout, Jean-Baptiste Gourraud, Antoine Deplagne, Philippe Ritter, Philippe Mabo, Dorothée Bazin-kara, Atman Haddj-Elmrabet, Bruno Seigneuric, Sylvain Ploux, Adrien Keller, Jean-Philippe Bourdenx, Laurence Jesel, Helene Savel, Claire Borni-Duval, Claire A. Martin, Philippe Maury, Frederic Sacher, Thierry Hannedouche, Sylvain Reuter, Virginie Rondeau, Pierre Bordachar, Frédéric Lavainne, J. Ott, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], CHU Strasbourg, Service de Néphrologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Service de néphrologie [Centre hospitalier de Haguenau], Centre hospitalier de Haguenau, Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique, CHU Bordeaux [Bordeaux], Service de Néphrologie-transplantation-dialyse [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Infectious and Parasitic diseases, Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Pontchaillou [Rennes], 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 ), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 ), and CHU Toulouse [Toulouse]
Subjects: medicine.medical_specialty, hemodialysis, implantable loop recorder, business.industry, medicine.medical_treatment, 030232 urology & nephrology, Early detection, sudden death, 030204 cardiovascular system & hematology, Sudden death, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Cardiac rhythm disturbances, Internal medicine, Implantable loop recorder, medicine, Cardiology, cardiovascular system, In patient, Hemodialysis, cardiovascular diseases, business, Dialysis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives - The aim of this study was to identify using implantable loop recorder (ILR) monitoring the mechanisms leading to sudden death (SD) in patients undergoing hemodialysis (HD). Background - SD accounts for 11% to 25% of death in HD patients. Methods - Continuous rhythm monitoring was performed using the remote monitoring capability of the ILR device in patients undergoing HD at 8 centers. Clinical, biological, and technical HD parameters were recorded and analyzed. Results - Seventy-one patients (mean age 65 ± 9 years, 73% men) were included. Left ventricular ejection fraction was 5.0 mmol/l, bicarbonate 11.5 g/dl, pre-HD systolic blood pressure >140 mm Hg, the longer interdialytic period, history of coronary artery disease, previous other arrhythmias, and diabetes mellitus. A higher risk for ventricular arrhythmia was associated with potassium
Published: 2018
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8. Hematopoietic stem cell transplantation for patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a retrospective study of 21 patients from SFGM-TC centers

Author: Alban Villate, Marie-Thérèse Rubio, Patrice Chevallier, Ibrahim Yakoub-Agha, Reza Tabrizi, Pierre-Simon Rohrlich, Nicolas Vallet, Louis Terriou, Jonathan Farhi, Deborah Desmier, Fiorenza Barraco, Raynier Devillier, Natacha Maillard, Mohamad Mohty, Régis Peffault de Latour, Annalisa Ruggeri, Patrice Ceballos, Steéphanie Nguyen, Gaelle Guillerm, Flore Sicre de Fontbrune, Michael Loschi, Xavier Poiré, Gérard Socié, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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 hospitalier universitaire de Nantes (CHU Nantes), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Hôpital l'Archet, Hôpital Lapeyronie [Montpellier] (CHU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Hemoglobinuria, Paroxysmal, CD59, Hematopoietic stem cell transplantation, Antibodies, Monoclonal, Humanized, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Registries, Online Only Articles, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Eculizumab, medicine.disease, Hemolysis, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Monoclonal, Paroxysmal nocturnal hemoglobinuria, Hemoglobinuria, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder which manifests with hemolysis (classical PNH) due to loss of expression of the CD55 and CD59 proteins, which leads to complement mediated cell lysis.[1][1] Despite being the only curative treatment for PNH
Published: 2018
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9. A new heterozygous mutation in GP1BA gene responsible for macrothrombocytopenia

Author: Gérard Sébahoun, Xavier Pillois, Véronique Baccini, Hana Raslova, Philippe Rameau, Denis Bernot, Marie-Christine Alessi, Noémie Saut, Dorsaf Ghalloussi, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Fibrinolyse et Pathologie Vasculaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Plateforme imagerie et cytométrie (PFIC), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie, Hôpital Nord [CHU - APHM], Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Goletto, Marie-Hélène, Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre recherche en CardioVasculaire et Nutrition (C2VN)
Subjects: Genetics, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, GP1BA gene, Platelet disorder, Heterozygote advantage, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 030204 cardiovascular system & hematology, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, PLATELET DISORDERS, PLATELETS, PLATELET GENETIC DISEASES, 03 medical and health sciences, 0302 clinical medicine, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation (genetic algorithm), PLATELET MEMBRANE, Platelet, MEGAKARYOCYTOPOIESIS, ComputingMilieux_MISCELLANEOUS, 030215 immunology, Heterozygous mutation, Megakaryocytopoiesis
Abstract: International audience
Published: 2018
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10. ITGA2B and ITGB3 gene mutations associated with Glanzmann thrombasthenia

Author: Alan T. Nurden, Xavier Pillois, Boullé, Christelle, Service d'hématologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-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), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Platelet aggregation, Integrin alpha2, Gene mutation, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, hemic and lymphatic diseases, Antithrombotic, Humans, Medicine, Platelet, ComputingMilieux_MISCELLANEOUS, business.industry, αiibβ3 integrin, Integrin beta3, Hematology, General Medicine, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030104 developmental biology, Article RECHERCHE, Glanzmann thrombasthenia, Mutation, Cancer research, business, Thrombasthenia, 030215 immunology
Abstract: Studies on Glanzmann thrombasthenia (GT) helped discover the αIIbβ3 integrin and led to successful antithrombotic therapy [1,2]. GT is defined by a lack of platelet aggregation with physiological a...
Published: 2018
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11. Dual- vs. single-chamber defibrillators for primary prevention of sudden cardiac death: long-term follow-up of the Défibrillateur Automatique Implantable—Prévention Primaire registry

Author: Frankie Beganton, Christophe Leclercq, Algalarrondo, Marie Cécile Perier, Eloi Marijon, Serge Boveda, Pierre Bordachar, Pascal Defaye, Dominique Babuty, Daniel Gras, Laurent Fauchier, Dai-Pp Investigators, Nicolas Sadoul, Kumar Narayanan, Jean-Claude Deharo, Didier Klug, Olivier Piot, Cardiac Stimulation and Rhythmology, CHU Grenoble, Clinique Pasteur et Groupe Rythmologie Stimulation Cardiaque/SFC, Clinique Pasteur [Toulouse], Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre cardiologique du Nord (CCN), Nouvelles Cliniques Nantaises, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Cardiologie [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'économie et de sociologie du travail (LEST), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Electronique et Systèmes de Télécommunications (LEST), Université de Brest (UBO)-Ecole Nationale Supérieure des Télécommunications de Bretagne-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Male, medicine.medical_specialty, Time Factors, Defibrillation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Electric Countershock, 030204 cardiovascular system & hematology, Prosthesis Design, Implantable cardioverter-defibrillator, law.invention, Sudden cardiac death, 03 medical and health sciences, 0302 clinical medicine, law, Risk Factors, Physiology (medical), Internal medicine, Cause of Death, Clinical endpoint, Medicine, Humans, 030212 general & internal medicine, Registries, Inappropriate shock, Aged, Retrospective Studies, Sudden death prevention, business.industry, Surrogate endpoint, Single-chamber defibrillator, Incidence (epidemiology), Arrhythmias, Cardiac, Middle Aged, medicine.disease, 3. Good health, Defibrillators, Implantable, Prosthesis Failure, Clinical trial, Primary Prevention, Death, Sudden, Cardiac, Treatment Outcome, Artificial cardiac pacemaker, Female, France, Cardiology and Cardiovascular Medicine, business, Dual-chamber defibrillator
Abstract: International audience; AIMS: Implantable cardioverter defibrillators (ICDs) are an effective primary prevention of sudden cardiac death. We examined whether dual-chamber (DC) ICDs confer a greater benefit than single-chamber (SC) ICDs, and compared the long-term outcomes of recipients of each type of device implanted for primary prevention.AbstractAIMS:Implantable cardioverter defibrillators (ICDs) are an effective primary prevention of sudden cardiac death. We examined whether dual-chamber (DC) ICDs confer a greater benefit than single-chamber (SC) ICDs, and compared the long-term outcomes of recipients of each type of device implanted for primary prevention.METHODS AND RESULTS:Between 2002 and 2012, the DAI-PP registry consecutively enrolled 1258 SC- and 1280 DC-ICD recipients at 12 French medical centres. The devices were interrogated at 4- to 6-month intervals during outpatient visits, with a focus on the therapies delivered. The study endpoints were incidence of appropriate therapies, ICD-related morbidity, and deaths from all and from specific causes. The mean age of the SC- and DC-ICD recipients was 59 ± 12 and 62 ± 11 years, respectively (P< 0.0001). The distribution of genders, New York Heart Association functional classes and glomerular filtration rates, and the rates of ischaemic vs. dilated cardiomyopathies and of defibrillation tests at implant, were similar in both study groups. The rates of periprocedural complications were 12.1% in the DC- vs. 8.8% in the SC-ICD groups (P= 0.008). Over a mean follow-up of 3.1 ± 2.2 years, pulse generators were replaced in 21.9% of the DC- vs. 13.6% of the SC-ICD group (P< 0.0001). The proportions of patients treated with ≥1 appropriate therapies (24.7 vs. 23.8%) and ≥1 inappropriate shocks (8.4 vs. 7.8%), and all-cause mortality (12.4 vs. 13.2%) were similar in both groups.CONCLUSION:In this large registry of ICD implanted for primary prevention, DC-ICDs were associated with higher rates of peri-implant complications and generator replacements, whereas the survival and rates of inappropriate shocks were similar in both groups.CLINICAL TRIAL NUMBER:NCT#01992458.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.
Published: 2017
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12. Multicenter investigation of an implantable cardioverter-defibrillator algorithm to detect oversensing

Author: Kenneth A. Ellenbogen, Pascal Defaye, Michel Haïssaguerre, Sylvain Ploux, Romain Eschalier, Philippe Ritter, Jayanthi N. Koneru, Nicolas Welte, Marc Strik, Pierre Mondoly, Antonio Frontera, Pierre Bordachar, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Cardiac Stimulation and Rhythmology, CHU Grenoble, Departament de Quimica, Universitat des Illes Balears, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], MUMC+: MA Med Staf Artsass Cardiologie (9), and RS: FHML non-thematic output
Subjects: Male, medicine.medical_treatment, Electrogram, 030204 cardiovascular system & hematology, Ventricular tachycardia, SHOCKS, 0302 clinical medicine, Devices, FAILURE, 030212 general & internal medicine, Lead (electronics), ComputingMilieux_MISCELLANEOUS, Middle Aged, Implantable cardioverter-defibrillator, Defibrillators, Implantable, 3. Good health, Algorithm, Ventricular Fibrillation, Cardiology, SecureSense, Equipment Failure, Female, France, Cardiology and Cardiovascular Medicine, Algorithms, medicine.medical_specialty, Medical device, Electric Countershock, External noise, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, T wave, medicine, Humans, Diagnostic Errors, Aged, business.industry, St Jude Medical, PERFORMANCE, Ventricular pacing, medicine.disease, Remote Sensing Technology, Ventricular fibrillation, Electrocardiography, Ambulatory, Tachycardia, Ventricular, Noise, business
Abstract: Background The SecureSense right ventricular (RV) lead noise discrimination algorithm is designed to detect lead fracture and other types of oversensing in order to decrease inappropriate therapy. Objective We studied the real-life accuracy of the SecureSense algorithm in implantable cardioverter-defibrillator (ICD) patients followed by remote monitoring across multiple centers. Methods Across 3 French centers, we studied 486 patients with a St Jude Medical device who were followed by remote monitoring and who had the SecureSense algorithm activated. We reviewed ≤10 of the most recent remote monitoring–transmitted electrograms of nonsustained oversensing, RV lead noise, and ventricular tachycardia/ventricular fibrillation that received therapy. Results SecureSense inhibited 22 inappropriate therapies (lead dysfunction in 10 cases, P-wave oversensing in 12 cases). A total of 57 patients (12%) sent ≥1 nonsustained oversensing episode (total of 393 episodes) with multiple etiologies: noise on the near-field channel (38%), oversensing of T waves during ventricular pacing (33%), oversensing of the sinus P wave (12%), and oversensing of the paced P wave (6%). Two episodes (0.5%) of nonsustained VT were undersensed by the far-field channel. Of 336 analyzed episodes of ventricular tachyarrhythmia, 15 episodes (4%) in 4 patients were related to oversensing of intrinsic P waves in 11 episodes or oversensing of external noise due to electrical cautery for the remaining 4 episodes. Conclusion Of ICD patients equipped with SecureSense, 12% developed episodes of oversensing. The SecureSense algorithm prevented inappropriate ICD therapies with accurate diagnosis of oversensing (caused by lead dysfunction or oversensing of physiological signals). P-wave oversensing in integrated bipolar leads, electrical cautery, and electromagnetic interference are prone to be missed by SecureSense.
Published: 2017
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13. Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients

Author: Arnaud Denis, Sylvain Ploux, Michel Haïssaguerre, Sana Amraoui, Romain Eschalier, Hubert Cochet, Josselin Duchateau, Saagar Mahida, Pierre Bordachar, Joost Lumens, Pierre Jaïs, Frederic Sacher, Xavier Pillois, Nicolas Derval, Philippe Ritter, Mélèze Hocini, Seigo Yamashita, Adlane Zemmoura, Yuki Komatsu, RS: CARIM - R2.09 - Cardiovascular system dynamics, Biomedische Technologie, Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Epicardial Mapping, Male, medicine.medical_treatment, Action Potentials, cardiac resynchronization therapy, heart failure, 030204 cardiovascular system & hematology, GUIDELINES, Ventricular Function, Left, Electrocardiography, Ventricular Dysfunction, Left, Basal (phylogenetics), 0302 clinical medicine, Heart Rate, 030212 general & internal medicine, mapping, COMMITTEE, OF-THE-ART, CARDIAC-RESYNCHRONIZATION THERAPY, Left bundle branch block, STATEMENT, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Homogeneous, Cardiology, cardiovascular system, Female, MULTIDETECTOR COMPUTED-TOMOGRAPHY, Intraventricular conduction delay, QRS DURATION, Electrophysiologic Techniques, Cardiac, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Heart Ventricles, Bundle-Branch Block, Cardiac resynchronization therapy, 03 medical and health sciences, QRS complex, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Conduction System, Predictive Value of Tests, Physiology (medical), Internal medicine, medicine, Humans, left bundle branch block, cardiovascular diseases, resynchronization, Aged, CLINICAL CARDIOLOGY, Bundle branch block, business.industry, Myocardium, Patient Selection, Arrhythmias, Cardiac, Stroke Volume, medicine.disease, Heart failure, MORPHOLOGY, BUNDLE-BRANCH-BLOCK, business
Abstract: International audience; T he deleterious impact of abnormal left ventricular (LV) activation in heart failure (HF) is well established. 1 Cardiac resynchronization therapy (CRT) represents a highly effective intervention in selected patients with HF and abnormal LV activation. The QRS pattern emerged as a more specific selection criterion in the latest American Heart Association (AHA)/European Heart Rhythm Association guidelines. These recommendations are based on multiple subgroup analyses demonstrating a clear benefit to CRT depending on the preim-plantation QRS pattern. 2-4 Therefore, patients with baseline left bundle branch block (LBBB) have a class I indication for CRT implantation and represent the best responders to CRT. Patients with narrow QRS currently have a class III indication for CRT as a result of large trial, demonstrating that CRT has a neutral or deleterious effect in this group of patients. 5-8 In patients with nonspecific intraventricular conduction delay (NICD), the guidelines are less clear, with a class IIa or IIb indication depending on the QRS duration. These patients represent a more heterogeneous group that is not clearly characterized. Its definition wide QRS without the appearance of left or right bundle block corresponds to a definition by default. Results obtained after CRT include only small numbers of patients, with no dedicated randomized studies. 9-11 The electrophysiological mechanisms of lack of response in narrow QRS and NICD are not well understood. The use of a more detailed electric activation map rather than QRS analysis could significantly enhance our understanding of the electric activation sequence in HF patients, especially in narrow QRS and NICD patients and, therefore, refine selection criteria for CRT. Original Article Background-In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. Methods and Results-Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P=0.0004; NICD versus LBBB, 4±2 versus 1±1; P=0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. Conclusions-In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy.
Published: 2017
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14. Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission

Author: Olivier Hermine, Denis Caillot, Karine Celli-Lebras, Céline Berthon, Arnaud Pigneux, Emmanuel Raffoux, Sylvie Chevret, Jean-Pierre Marolleau, Oumedaly Reman, Emilie Lemasle, Hervé Dombret, Norbert Vey, Stéphane de Botton, Xavier Thomas, Jean-Yves Cahn, Marc A. Simon, Claude Preudhomme, Norbert Ifrah, Christian Recher, Sylvie Castaigne, Christine Terré, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Georges Clémenceau, CH de Valenciennes, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CRLCC Henri Becquerel, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Versailles (CHV), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, CHU Versailles, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: Male, Cancer Research, Survival, medicine.medical_treatment, Phases of clinical research, Hematopoietic stem cell transplantation, Older Patients, Gastroenterology, Trial, 0302 clinical medicine, Adenine nucleotide, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, Repetitive Cycles, Clofarabine, Cumulative incidence, Adenine Nucleotides, Hazard ratio, Colony-Stimulating Factor, Cytarabine, Hematopoietic Stem Cell Transplantation, Acute Myelogenous Leukemia, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, High-Dose Cytarabine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, Chemotherapy, Group-B, business.industry, Induction Therapy, Surgery, Transplantation, Consolidation Chemotherapy, Arabinonucleosides, business, 030215 immunology
Abstract: Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment × SCT interaction term. Results At 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment × SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles. Conclusion These results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission.
Published: 2017
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15. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma

Author: Michel, Attal, Valerie, Lauwers-Cances, Cyrille, Hulin, Xavier, Leleu, Denis, Caillot, Martine, Escoffre, Bertrand, Arnulf, Margaret, Macro, Karim, Belhadj, Laurent, Garderet, Murielle, Roussel, Catherine, Payen, Claire, Mathiot, Jean P, Fermand, Nathalie, Meuleman, Sandrine, Rollet, Michelle E, Maglio, Andrea A, Zeytoonjian, Edie A, Weller, Nikhil, Munshi, Kenneth C, Anderson, Paul G, Richardson, Thierry, Facon, Hervé, Avet-Loiseau, Jean-Luc, Harousseau, Philippe, Moreau, P, Zunic, Pôle Institut Universitaire du Cancer - Oncopole [CHU Toulouse] (Pôle IUC - Oncopole), CHU Toulouse [Toulouse]-Oncopole de Toulouse, Service d'Epidémiologie, CHU Toulouse [Toulouse], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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, Hôpital Universitaire de Caen, Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire d'Hématologie biologique, Institut Curie [Paris], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Dana-Farber Cancer Institute [Boston], Hôpital Claude Huriez [Lille], CHU Lille, Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Hôtel-Dieu de Nantes, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut Curie, Institut Jules Bordet, Hôpital Claude Huriez, and Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, Oncology, Follow-Up, Salvage therapy, Kaplan-Meier Estimate, Stem-Cell Transplantation, Dexamethasone, Bortezomib, 0302 clinical medicine, Maintenance therapy, Antineoplastic Combined Chemotherapy Protocols, Autologous Transplantation, Medicine, Lenalidomide, Multiple myeloma, Initial Treatment, Cancer, Phase-Iii, Induction Chemotherapy, General Medicine, Middle Aged, Daratumumab Monotherapy, Combined Modality Therapy, Thalidomide, 3. Good health, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Female, Adults with multiple myeloma, Multiple Myeloma, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Disease-Free Survival, Article, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, Humans, Autologous transplantation, Aged, Salvage Therapy, Transplantation, Diagnosed Multiple-Myeloma, Prednisone Plus Thalidomide, business.industry, Elderly-Patients, medicine.disease, Surgery, Randomized Controlled-Trial, business, Stem Cell Transplantation, 030215 immunology
Abstract: International audience; BackgroundHigh-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation.MethodsWe randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival.ResultsMedian progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazard ratio for disease progression or death, 0.65; P
Published: 2017
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16. 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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17. Implantable cardioverter-defibrillator therapy among patients with non-ischaemic vs. ischaemic cardiomyopathy for primary prevention of sudden cardiac death

Author: Christophe Leclercq, A. Bouzeman, Dominique Babuty, Frederic Treguer M.D., Pascal Defaye, Daniel Gras, Olivier Piot, Vincent Algalarrondo, Laurent Fauchier, Nicolas Sadoul, Dai-Pp Investigators, Nelly Amara, Denis Amet, Serge Boveda, Pierre Bordachar, Marie-Cécile Perier, Eloi Marijon, Didier Klug, Jean-Claude Deharo, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Clinique Pasteur [Toulouse], Cardiac Stimulation and Rhythmology, CHU Grenoble, Laboratoire des Écoulements Géophysiques et Industriels [Grenoble] (LEGI ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Electronique des Systèmes TEmps Réel (LESTER), Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre cardiologique du Nord (CCN), Nouvelles Cliniques Nantaises, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Service de Cardiologie B, Clinique Saintt Joseph, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Centre Hospitalier de Versailles André Mignot (CHV)
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Electric Countershock, Myocardial Ischemia, Cardiomyopathy, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, [SHS]Humanities and Social Sciences, Sudden cardiac death, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cause of Death, Physiology (medical), Internal medicine, medicine, Humans, Sinus rhythm, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, Proportional Hazards Models, Retrospective Studies, Cause of death, Ejection fraction, Ischemic cardiomyopathy, business.industry, Hazard ratio, Middle Aged, medicine.disease, Implantable cardioverter-defibrillator, Defibrillators, Implantable, Primary Prevention, Death, Sudden, Cardiac, Treatment Outcome, Cardiology, Female, France, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Aim The magnitude of benefit related to implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death (SCD) in non-ischaemic cardiomyopathy (NICM) and ischaemic cardiomyopathy (ICM) has not been evaluated extensively in clinical practice. Methods and results Of the 5539 consecutive patients enrolled in the multicentre Defibrillateur Automatique Implantable-Prevention Primaire (DAI-PP) study (2002-12), 5485 patients (with information on underlying heart disease) were included in the present analysis: 2181 (39.8%) had NICM and 3304 (60.2%) had ICM. ICM patients were older (63.7 ±10.3 vs. 60.6 ± 12.2 years, P
Published: 2017
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18. Impact of body-surface area on patients' outcome in younger adults with acute myeloid leukemia

Author: Yosr Hicheri, Norbert Vey, Jean-Yves Cahn, Patrice Chevallier, Fabrice Larosa, Norbert Ifrah, Martin Carre, Emmanuel Gyan, Bouscary Didier, Chantal Himberlin, Bruno Lioure, Gaelle Guillerm, Christian Recher, Mario Ojeda-Uribe, Marie C. Béné, Marc Bernard, Caroline Bonmati, Arnaud Pigneux, Mathilde Hunault-Berger, Xavier Cahu, Jacques Delaunay, Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [Nantes], Centre d'investigation clinique en cancérologie (CI2C), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Service d'hématologie, 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), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], PRES Université Nantes Angers Le Mans (UNAM), Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Rennes (UR)-Hôpital Pontchaillou, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Body Surface Area, medicine.medical_treatment, [SDV]Life Sciences [q-bio], acute myeloid leukemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Multicenter Studies as Topic, Medicine, Body Weights and Measures, Young adult, Dose intensity, Survival analysis, Body surface area, Chemotherapy, business.industry, Remission Induction, Age Factors, Myeloid leukemia, Hematology, General Medicine, Survival Analysis, 3. Good health, Surgery, Leukemia, Myeloid, Acute, Treatment Outcome, Clinical Trials, Phase III as Topic, Postremission Therapy, dose reduction, Younger adults, 030220 oncology & carcinogenesis, Cytarabine, Female, body-surface area, business, 030215 immunology, medicine.drug
Abstract: International audience; OBJECTIVES: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, and clinical outcome. METHODS: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered. RESULTS: Very high BSA (≥2.15 m(2) ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5-years OS of 27%) compared to the low (BSA≤1.5 m(2) ), intermediate (1.5 m(2)
Published: 2017
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19. No evidence of hepatitis B virus reactivation among liver transplant recipients treated with interferon- free regimens for hepatitis C virus recurrence (ANRS CO23 CUPILT Cohort)

Author: Mouna, Lina, Rossignol, Emilie, Tateo, Mariagrazia, Duclos-Vallee, Jean-Charles, Duvoux, Christophe, Durand, Francois, Tran, Albert, Radenne, Sylvie, Canva-Delcambre, Valerie, Houssel-Debry, Pauline, Dumortier, Jérôme, Conti, Filomena, De Ledinghen, Victor, Leroy, Vincent, Kamar, Nassim, Di Martino, Vincent, Moreno, Christophe, Fridlund, Danielle M. Botta, D'Alteroche, Louis, Lebray, Pascal, perre, philippe, Besch, Camille, Silvain, Christine, Habersetzer, François, Debette-Gratien, Maryline, Abergel, Armando, Diallo, Alpha, Roque-Afonso, Anne Marie, Pageaux, Georges-Philippe, Jonchère, Laurent, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), DHU Hepatinov, Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hépatogastroentérologie [Hôpital de la Croix-Rousse, Hospices Civils de Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Service d'hépatogastroentérologie [Hôpital Edouard Herriot, Hospices Civils de Lyon], Hôpital Edouard Herriot [CHU - HCL], Hôpital St Antoine, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Michallon, CHU Toulouse [Toulouse], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Marseille, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHD Vendee (La Roche Sur Yon), Service d’Hépatogastroentérologie, NHC, CHU de Strasbourg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, CHU Clermont-Ferrand, ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Lapeyronie [Montpellier] (CHU), Novartis, Astellas, Roche, MSD, GSK, Gilead, Supersonic Imagine, Janssen, Abbvie, Schering-Plough, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

20. Platelet function and microparticle levels in atrial fibrillation: Changes during the acute episode

Author: Olivier Bernus, Michel Haïssaguerre, Frederic Sacher, Jean Marc Sellal, Line Pourtau, Paquita Nurden, Gisèle Clofent-Sanchez, Mélèze Hocini, Françoise Dignat-George, Philippe Poncelet, Romaric Lacroix, Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), BIOCYTEX, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Xavier Arnozan, CHU Bordeaux [Bordeaux]-Hôpital Xavier Arnozan, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], and CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2
Subjects: Blood Platelets, Male, 0301 basic medicine, Platelets, medicine.medical_specialty, Platelet Aggregation, Microparticles fibrinolytic activity, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, Tissue factor, 0302 clinical medicine, Thrombin, Von Willebrand factor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell-Derived Microparticles, Internal medicine, Humans, Medicine, Platelet, Thrombin receptor, Ristocetin, Microparticle procoagulant activity, biology, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Atrial fibrillation, Middle Aged, Platelet Activation, medicine.disease, 030104 developmental biology, chemistry, Coagulation, Ketoprofen, Hemostasis, Immunology, Catheter Ablation, Cardiology, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: International audience; Background: Thrombotic risk constitutes a major complication of atrial fibrillation (AF). Platelets and microparti-cles (MPs) are important for hemostasis and thrombosis, however their participation during AF is not well known. The aim of this study was to characterize platelet function and MPs procoagulant and fibrinolytic activity in AF patients and to determine the effects of an acute-AF episode. Methods: Blood was collected from paroxysmal (21) and persistent (16) AF patients referred for AF catheter ab-lation. Ten patients in sinus rhythm for 10 days were induced in AF allowing comparisons of left atrium samples before and after induction. Platelet aggregation with ADP, TRAP, collagen, and ristocetin was studied. Platelet surface expression of PAR-1, αIIbβ3, GPIb and P-selectin were evaluated by flow cytometry, and MPs-associated procoagulant and fibrinolytic activity levels were determined by functional assays. Results: A specific reduction in platelet aggregation to TRAP, activating the thrombin receptor PAR-1, was found in all AF patients. No differences in platelet receptor expression were found. Yet, after acute-induced AF, the platelet response was improved. Furthermore, a significant decrease of left atrium tissue factor-dependent procoagulant activity of MPs was observed. Conclusion: Acute episodes of AF results in a decrease in MPs-associated tissue factor activity, possibly corresponding to consumption, which in turn favors coagulation and the local production of thrombin. A decreased platelet basal aggregation to TRAP may result from PAR1 desensitization, whereas the improved response after an induced episode of AF suggests activation of coagulation and PAR1 re-sensitization.
Published: 2017
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21. Clinical and Laboratory Findings in Patients with δ-Storage Pool Disease: A Case Series

Author: Fabien Selle, Marie Tuffigo, Xavier Pillois, Mathieu Fiore, Jean-François Viallard, Chloé James, Marie-Christine Alessi, Université de Bordeaux (UB), 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), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, and ALESSI, Marie-Christine
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Blood Platelets, Male, Platelet Storage Pool Deficiency, Pathology, medicine.medical_specialty, Platelet Aggregation, Mepacrine, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Article CLINIQUE, Humans, Medicine, Platelet, Platelet activation, Platelet storage pool deficiency, CD63, biology, electron microscopy, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, dense granules, 3. Good health, Bleeding diathesis, bleeding score, Microscopy, Electron, Glycoprotein Ib, 030220 oncology & carcinogenesis, biology.protein, Female, platelet δ-storage pool disease, Cardiology and Cardiovascular Medicine, business, platelet function testing, medicine.drug
Abstract: International audience; Platelet δ-storage pool disease (δ-SPD) is a platelet function disorder characterized by a reduction in the number or content of dense granules. Reports on δ-SPD are mostly limited to case presentations. We aimed to retrospectively describe a series of patients with δ-SPD to better characterize the disease. We studied 16 patients with congenital or acquired δ-SPD. Lumiaggregometry, α- and δ-granules content, platelet ultrastructure, αIIbβ3 integrin, and glycoprotein Ib (GPIb) activation were assessed. Most of the patients generally demonstrate mild to moderate bleeding diathesis. Platelet aggregation studies showed moderate abnormalities with variable profiles, while all the individuals had almost complete absence of adenosine triphosphate release. Mepacrine capture, CD63 expression, and study of dense granules by electron microscopy enabled to distinguish different subtypes of δ-SPD with quantitative or qualitative defect. Surprisingly, significantly decreased GPIb expression levels after platelet activation with thrombin receptor activating peptide 50 μM were found, suggesting that GPIb-impaired mobilization may represent an additional feature of the disorder. In conclusion, δ-SPD represents a complex disorder with various clinical and biological aspects, requiring a great deal of expertise to be properly diagnosed.
Published: 2017
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22. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association

Author: Diane Damotte, Aspasia Stamatoullas, Herve Ghesquieres, Laurent Martin, Camille Laurent, Peggy Dartigues, Pierre Hirsch, Thierry Jo Molina, Clémentine Sarkozy, Anne-Sophie Michallet, Jehan Dupuis, Bettina Fabiani, Alexandra Traverse-Glehen, Gilles Salles, Franck Morsschauser, Marie Maerevoet, M. Parrens, Maria Gomes da Silva, Krimo Bouabdallah, Bertrand Coiffier, 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 ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Léon Bérard [Lyon], CHU Henri Mondor, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ), CRLCC Henri Becquerel, Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Instituto Português de Oncologia de Lisboa Francisco Gentil, Institut Jules Bordet, Departement de Pathologie, Institut Claudius Regaud,Toulouse, Fédération Nationale des Centres de Lutte contre le Cancer, Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, Hospices Civils de Lyon ( HCL ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor [Créteil], Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
Subjects: Male, BEACOPP, Biopsy, medicine.medical_treatment, Gastroenterology, 0302 clinical medicine, Bone Marrow, Recurrence, immune system diseases, hemic and lymphatic diseases, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Articles, Hematology, Middle Aged, Prognosis, Combined Modality Therapy, Immunohistochemistry, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Disease Progression, Female, Rituximab, medicine.drug, Adult, medicine.medical_specialty, Lymphoma, B-Cell, Adolescent, Mediastinal Neoplasms, Gray zone lymphoma, Immunophenotyping, Young Adult, 03 medical and health sciences, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Biomarkers, Tumor, medicine, Humans, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, business.industry, medicine.disease, Survival Analysis, Surgery, Lymphoma, Radiation therapy, Regimen, ABVD, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, 030215 immunology
Abstract: International audience; Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lym-phoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalat-ed BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
Published: 2016
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23. Comparison of Outcome of Possible Versus Definite Infective Endocarditis Involving Native Heart Valves

Author: Boveda, Serge, Narayanan, Kumar, Jacob, Sophie, Providencia, Rui, Algalarrondo, Vincent, Bouzeman, Abdeslam, Beganton, Frankie, Defaye, Pascal, Perier, Marie-Cécile, Sadoul, Nicolas, Piot, Olivier, Klug, Didier, Gras, Daniel, Fauchier, Laurent, Bordachar, Pierre, Babuty, Dominique, Deharo, Jean-Claude, Leclercq, Christophe, Marijon, Eloi, Pericart, Lauriane, Bernard, Anne, Bourguignon, Thierry, Bernard, Louis, Angoulvant, Denis, Clementy, Nicolas, Clinique Pasteur [Toulouse], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Barts Heart Centre [London, UK] (St Bartholomew’s Hospital), Barts Health NHS Trust [London, UK], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier de Versailles André Mignot (CHV), Cardiac Stimulation and Rhythmology, CHU Grenoble, Laboratoire d'Electronique des Systèmes TEmps Réel (LESTER), Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS), Centre cardiologique du Nord (CCN), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nouvelles Cliniques Nantaises, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire des Écoulements Géophysiques et Industriels [Grenoble] (LEGI ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Service de Médecine Interne et Maladies Infectieuses [Tours], Cellules Dendritiques, Immunomodulation et Greffes, and CHU Trousseau [Tours]
Subjects: Male, medicine.medical_specialty, Time Factors, Heart Valve Diseases, 030204 cardiovascular system & hematology, Duke criteria, [SHS]Humanities and Social Sciences, Academic institution, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Mitral valve, Cause of Death, medicine, Humans, 030212 general & internal medicine, Heart valve, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Endocarditis, business.industry, Middle Aged, medicine.disease, Prognosis, Heart Valves, Survival Rate, medicine.anatomical_structure, Echocardiography, Infective endocarditis, Cardiology, Female, France, Morbidity, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: There are very few data on the prognosis of possible versus definite infective endocarditis (IE). We studied data from 365 consecutive patients with IE involving native heart valve seen in an academic institution from 1990 to 2012. Patients were classified according to the modified Duke criteria for IE: patients with possible IE (n = 101, 28%) and those with definite IE (n = 264, 72%). Patients with possible IE were older than those with definite IE (66 ± 15 vs 62 ± 16, p = 0.05). A causative microorganism was identified in 66% of patients with possible IE versus all patients with definite IE (p0.0001) and only 41% had major echocardiographic criteria (vs 100%; p0.0001). Overall, 139 patients died over a mean ± SD follow-up of 3.9 ± 4.5 years (median 2.2, interquartile range 5.9 years). Patients with possible and definite IE had a similar risk of death. Independent predictors of long-term mortality were increasing age (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01 to 1.04; p = 0.0009), vegetation length15 mm (HR 1.87, 95% CI 1.14 to 3.06; p = 0.01), and stroke (HR 4.10, 95% CI 1.84 to 9.17; p = 0.0006), whereas infection of mitral valve (HR 0.57, 95% CI 0.34 to 0.94; p = 0.03) and surgery (HR 0.43, 95% CI 0.19 to 0.99; p = 0.05) were associated with a better prognosis. Patients with definite IE and those with possible IE who did not undergo surgery had a worse prognosis than their counterparts with surgery. In conclusion, unselected patients with possible IE (Duke criteria) had a similar prognosis than those with definite IE.
Published: 2016
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24. Lung morphology assessment of cystic fibrosis using MRI with ultra-short echo time at submillimeter spatial resolution

Author: M. Fayon, Fanny Menut, Michel Montaudon, Patrick Berger, Gaël Dournes, Olivier Corneloup, Marjorie Salel, Jean-François Chateil, Julie Macey, François Laurent, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Physiopathologie de la réactivité bronchique et vasculaire, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Cystic Fibrosis, Intraclass correlation, Concordance, [SDV]Life Sciences [q-bio], Contrast Media, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Imaging, Three-Dimensional, medicine, Humans, Radiology, Nuclear Medicine and imaging, Child, Lung, Neuroradiology, Reproducibility, Bronchiectasis, medicine.diagnostic_test, business.industry, Ultrasound, Reproducibility of Results, Magnetic resonance imaging, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030228 respiratory system, ROC Curve, Female, Radiology, business, Tomography, X-Ray Computed, Kappa
Abstract: We hypothesized that non-contrast-enhanced PETRA (pointwise encoding time reduction with radial acquisition) MR (magnetic resonance) sequencing could be an alternative to unenhanced computed tomography (CT) in assessing cystic fibrosis (CF) lung structural alterations, as well as compared agreements and concordances with those of conventional T1-weighted and T2-weighted sequences. Thirty consecutive CF patients completed both CT and MRI the same day. No contrast injection was used. Agreement in identifying structural alterations was evaluated at the segmental level using a kappa test. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess concordances and reproducibility in Helbich-Bhalla disease severity scoring. Agreement between PETRA and CT was higher than that of T1- or T2-weighted sequences, notably in assessing the segmental presence of bronchiectasis (Kappa = 0.83; 0.51; 0.49, respectively). The concordance in Helbich-Bhalla scores was very good using PETRA (ICC = 0.97), independently from its magnitude (mean difference (MD) = -0.3 [-2.8; 2.2]), whereas scoring was underestimated using both conventional T1 and T2 sequences (MD = -3.6 [-7.4; 0.1]) and MD = -4.6 [-8.2; -1.0], respectively). Intra- and interobserver reproducibility were very good for all imaging modalities (ICC = 0.86-0.98). PETRA showed higher agreement in describing CF lung morphological changes than that of conventional sequences, whereas the Helbich-Bhalla scoring matched closely with that of CT. • Spatial resolution of lung MRI is limited using non-ultra-short TE MRI technique • Ultra-short echo time (UTE) technique enables submillimeter 3D-MRI of airways • 3D-UTE MRI shows very good concordance with CT in assessing cystic fibrosis • Radiation-free 3D-UTE MRI enables the Helbich-Bhalla scoring without a need for contrast injection
Published: 2016
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25. Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome

Author: Anne-Sophie Morin, Marc Michel, Daniel Adoue, Bertrand Godeau, Olivier Fain, Nathalie Costedoat-Chalumeau, Brigitte Pan-Petesch, Nadine Magy-Bertrand, Bernard Bonnotte, Clementine Nordon, Karim Sacre, François Lefrère, Mehdi Khellaf, Jean-François Viallard, Jean-Marc Durand, Lamiae Grimaldi-Bensouda, Lucien Abenhaim, Nathalie Morel, Antoinette Perlat, Philippe Quittet, LASER Paris, CHU Henri Mondor, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], 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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Saint-Eloi, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Morvan [Brest], Service d'Accueil des Urgences (Urgences - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pontchaillou [Rennes], 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), Département de Biothérapie [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)-Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Médecine Interne [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Service d'ORL et de chirurgie cervicale, CHU Grenoble, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), London School of Hygiene and Tropical Medicine (LSHTM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), HAL UPMC, Gestionnaire, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], 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), Hôpital Saint Eloi (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Henri Mondor [Créteil], 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), Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Toulouse III - Paul Sabatier ( UPS ), 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 Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Médecine interne [CHU St-Antoine], CHU Saint-Antoine [APHP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hôpital Jean Verdier, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service d'Accueil des Urgences ( Urgences - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri-Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Anti-nuclear antibody, Adolescent, [SDV]Life Sciences [q-bio], Logistic regression, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Odds Ratio, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Humans, Prospective Studies, Registries, Risk factor, Young adult, Family history, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Purpura, Thrombocytopenic, Idiopathic, business.industry, Disease Management, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Odds ratio, Articles, Middle Aged, 3. Good health, Surgery, Patient Outcome Assessment, Phenotype, 030220 oncology & carcinogenesis, Population Surveillance, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Cohort study, Follow-Up Studies
Abstract: for the PGRx-ITP Study Group; International audience; This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×109/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome.
Published: 2016
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26. Primary Prevention Implantable Cardioverter Defibrillator (ICD) Therapy in Women-Data From a Multicenter French Registry

Author: Rui Providência, Eloi Marijon, Pier D. Lambiase, Abdeslam Bouzeman, Pascal Defaye, Didier Klug, Denis Amet, Marie‐Cécile Perier, Daniel Gras, Vincent Algalarrondo, Jean‐Claude Deharo, Christophe Leclercq, Laurent Fauchier, Dominique Babuty, Pierre Bordachar, Nicolas Sadoul, Olivier Piot, Serge Boveda, Rui Providencia, Frankie Beganton, Marie‐Cecile Perier, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cardiac Stimulation and Rhythmology, CHU Grenoble, Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvelles Cliniques Nantaises, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre cardiologique du Nord (CCN), Clinique Pasteur et Groupe Rythmologie Stimulation Cardiaque/SFC, Clinique Pasteur [Toulouse], 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), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), 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 ), Service de cardiologie et maladies vasculaires, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU de Tours, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre cardiologique du Nord, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1
Subjects: Male, Time Factors, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], heart failure, shock, 030204 cardiovascular system & hematology, Arrhythmias, Cardiac Resynchronization Therapy, 0302 clinical medicine, Risk Factors, Arrhythmia and Electrophysiology, 030212 general & internal medicine, Registries, death, sudden, Original Research, Hazard ratio, Middle Aged, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, Prosthesis Failure, Primary Prevention, Treatment Outcome, Cohort, Cardiology, Female, France, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Cardiac resynchronization therapy, Electric Countershock, Prosthesis Design, 03 medical and health sciences, Sex Factors, Internal medicine, death, medicine, Humans, Cardiac Resynchronization Therapy Devices, Healthcare Disparities, Aged, Retrospective Studies, sudden, [ SDV ] Life Sciences [q-bio], business.industry, Retrospective cohort study, Odds ratio, Health Status Disparities, medicine.disease, mortality, Death, Sudden, Cardiac, Heart failure, business, Catheter Ablation and Implantable Cardioverter-Defibrillator
Abstract: Background There are limited data describing sex specificities regarding implantable cardioverter defibrillators (ICDs) in the real‐world European setting. Methods and Results Using a large multicenter cohort of consecutive patients referred for ICD implantation for primary prevention (2002–2012), in ischemic and nonischemic cardiomyopathy, we examined the sex differences in subjects' characteristics and outcomes. Of 5539 patients, only 837 (15.1%) were women and 53.8% received cardiac resynchronization therapy. Compared to men, women presented a significantly higher proportion of nonischemic cardiomyopathy (60.2% versus 36.2%, P 120 ms: 74.6% versus 68.5%, P =0.003), higher New York Heart Association functional class (≥III in 54.2%♀ versus 47.8%♂, P =0.014), and lower prevalence of atrial fibrillation (18.7% versus 24.9%, P P P =0.492), early complications (odds ratio=1.00, 95% CI 0.75–1.32, P =0.992), and all‐cause mortality (hazard ratio=0.87 95% CI 0.66–1.15, P =0.324). Analysis of sex‐by‐ cardiac resynchronization therapy interaction shows than female cardiac resynchronization therapy recipients experienced fewer appropriate therapies than men (hazard ratio=0.62, 95% CI 0.50–0.77; P P =0.034). Conclusions In our real‐life registry, women account for the minority of ICD recipients and presented with a different clinical profile. Whereas female cardiac resynchronization therapy recipients had a lower incidence of appropriate ICD therapies and all‐cause death than their male counterparts, the observed rates of inappropriate shocks and early complications in all ICD recipients were comparable. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT01992458.
Published: 2016
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27. Impact of early complications on outcomes in patients with implantable cardioverter-defibrillator for primary prevention

Author: Maria Soledad Ascoeta, Marie-Cécile Perier, Olivier Piot, Daniel Gras, Laurent Fauchier, Nicolas Sadoul, Pascal Defaye, Didier Klug, Frankie Beganton, Eloi Marijon, Serge Boveda, Vincent Algalarrondo, Dominique Babuty, Christophe Leclercq, Jean-Claude Deharo, Pierre Bordachar, Centre cardiologique du Nord (CCN), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Nouvelles Cliniques Nantaises, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Clinique Pasteur et Groupe Rythmologie Stimulation Cardiaque/SFC, Clinique Pasteur [Toulouse], Editorial support on the final version of the paper was provided by MedLink Healthcare Communications Ltd and was funded by the authors. ADREC (Association Dyonisienne de Recherche et Enseignement de Cardiologie) provided secretarial assistance., Centre cardiologique du Nord, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire [Grenoble] ( CHU ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), 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 ), Service de cardiologie et maladies vasculaires, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU de Tours, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1
Subjects: Male, Pediatrics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Postoperative Complications, Risk Factors, Medicine, 030212 general & internal medicine, Registries, education.field_of_study, Hematoma, Primary prevention, Sudden death, Incidence (epidemiology), Incidence, Middle Aged, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, Female, France, Cardiology and Cardiovascular Medicine, Cardiomyopathy, Dilated, medicine.medical_specialty, Population, Cardiac resynchronization therapy, Electric Countershock, Risk Assessment, 03 medical and health sciences, Physiology (medical), Humans, Mortality, education, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Implantable cardiac-defibrillator, Odds ratio, medicine.disease, Survival Analysis, Equipment Failure Analysis, Death, Sudden, Cardiac, Tachycardia, Ventricular, Morbidity, Complication, business
Abstract: International audience; Background - The lifesaving benefit of implantable cardioverter-defibrillators (ICDs) has been demonstrated. Their use has increased considerably in the past decade, but related complications have become a major concern. Objective - The purpose of this study was to assess the incidence and effect on outcomes of early (≤30 days) complications after ICD implantation for primary prevention in a large French population. Methods - We analyzed data from 5539 patients from the multicenter French DAI-PP (Défibrillateur Automatique Implantable-Prévention Primaire) registry (2002-2012) who had coronary artery disease or dilated cardiomyopathy and were implanted with an ICD for primary prevention. Results - Overall, early complications occurred in 707 patients (13.5%), mainly related to lead dislodgment or hematoma (57%). Independent factors associated with occurrence of early complications were severe renal impairment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.17-2.37, P = .02), age ≥75 years (OR 1.01, 95% CI 1.00-1.02, P = .03), cardiac resynchronization therapy (OR 1.58, 95% CI 1.16-2.17, P = .01), and anticoagulant therapy (OR 1.28, 95% CI 1.02-1.61, P = .03). During a mean ± SD follow-up of 3.1 ± 2.3 years, 824 (15.8%) patients experienced ≥1 late complication (>30 days), and 782 (14.9%) patients died. After adjustment, early complications remained associated with occurrence of late complications (OR 2.15, 95% CI 1.73-2.66, P < .0001) and mortality (OR 1.70, 95% CI 1.34-2.17, P = .003). Conclusion - Early complications are common after ICD implantation for primary prevention, occurring in 1 in 7 patients, and are associated with an increased risk of late complications and overall mortality. Further studies are needed to investigate the underlying mechanisms of such associations.
Published: 2016
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28. The psychological impact of implantable cardioverter defibrillator implantation on Brugada syndrome patients

Author: Dominique Babuty, Delphine Plassard-Kerdoncuf, Gilles Lande, Christine Fruchet, Vincent Probst, Hervé Le Marec, Frederic Sacher, Béatrice Guyomarch, Philippe Mabo, Jacques Mansourati, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Male, Pediatrics, Heart disease, medicine.medical_treatment, 030204 cardiovascular system & hematology, MESH: Brugada Syndrome, MESH: Health Surveys, 0302 clinical medicine, Quality of life, Risk Factors, MESH: Risk Factors, Surveys and Questionnaires, 030212 general & internal medicine, Brugada Syndrome, Brugada syndrome, MESH: Aged, education.field_of_study, MESH: Middle Aged, Middle Aged, Implantable cardioverter-defibrillator, Defibrillators, Implantable, 3. Good health, Cardiology, Female, France, medicine.symptom, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, SF-36, Population, Sudden death, Asymptomatic, MESH: Defibrillators, Implantable, 03 medical and health sciences, Physiology (medical), Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, education, Aged, MESH: Humans, business.industry, MESH: Questionnaires, MESH: Quality of Life, MESH: Adult, medicine.disease, Health Surveys, MESH: Male, MESH: France, Quality of Life, business, MESH: Female
Abstract: International audience; AIMS: Brugada syndrome (BrS) is a hereditary arrhythmic disease, responsible for sudden death in patients without known heart disease. An implantable cardioverter defibrillator (ICD) is recommended in patients at high risk of sudden death, but the resulting psychological impact has never been studied. The aim of our study was to assess the impact on quality of life of BrS and ICD implantation. METHODS AND RESULTS: Patients were selected from the reference centre for hereditary arrhythmic disease database in Nantes. This population was divided into three groups: Group 1 (G1), symptomatic implanted patients; Group 2 (G2), asymptomatic implanted patients; and Group 3 (G3), asymptomatic patients without ICD. One hundred and ninety questionnaires [36-item short-form health survey (SF-36) and subsidiary questions] were analysed (60 in G1, 78 in G2, and 52 in G3). We failed to identify any difference in the evaluation of the SF-36 between the three groups and the SF-36 score was similar to the French population score. However, specific questions regarding tolerance of the ICD showed that ICD implantation resulted in significant negative impact, especially for professional careers and purchasing insurance, even though the patient considered ICD implantation as reassuring. CONCLUSION: Whatever the group, BrS patients have a good quality of life with no difference between implanted and non-implanted patients. However, ICD implantation is accompanied by difficulties in their social and professional life. This work emphasizes the need to propose specific recommendations applicable to insurance to reduce the complications experienced by these patients.
Published: 2011
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29. Therapeutic drug monitoring of mycophenolate mofetil and enteric-coated mycophenolate sodium in patients with systemic lupus erythematosus

Author: Sarah Djabarouti, Pierre Duffau, Jean-François Viallard, Estibaliz Lazaro, Candice Chapouly, Marie-Claude Saux, C. Greib, Jean-Luc Pellegrin, Dominique Breilh, 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 de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service de médecine interne et maladies infectieuses, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Adaptation cardiovasculaire à l'ischémie, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de médecine interne, maladies infectieuses et systémiques, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Médecine Interne, Coordination Régionale de la lutte contre l'infection due au VIH (COREVIH), COREVIH, Département de pharmacocinétique et pharmacologie clinique, Service de pharmacocinétique et de pharmacie clinique, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], PENIGAUD, LAURE, and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Cmax, Administration, Oral, Renal function, Pharmacology, Mycophenolate, 030226 pharmacology & pharmacy, Gastroenterology, Mycophenolic acid, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Internal medicine, Humans, Lupus Erythematosus, Systemic, Medicine, Pharmacology (medical), skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Lupus erythematosus, medicine.diagnostic_test, business.industry, Mycophenolate Sodium, General Medicine, Middle Aged, Mycophenolic Acid, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Therapeutic drug monitoring, Area Under Curve, Female, Tablets, Enteric-Coated, Drug Monitoring, business, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.drug
Abstract: Mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), is used to treat systemic lupus erythematosus (SLE). MMF and EC-MPS pharmacokinetics were examined to devise guidance for therapeutic drug monitoring (TDM) for SLE patients with normal renal function.This observational study included 21 patients receiving MMF (1000 mg twice daily) and 14 taking EC-MPS (720 mg twice daily). MPA AUC between 0 and 12 h (AUC(0-12h)), C(max), T(max), and 12-h trough concentrations (C(12h)) were determined.Means of dose-normalized MMF- or EC-MPS-MPA C(max) were 64.6 +/- 25 and 61.4 +/- 27.1 h mg/l, respectively. MPA T(max) for EC-MPS was longer and more variable than for MMF. MMF-MPA AUC(0-12h) and C(12h) were correlated (r = 0.78, p = 0.0001), but EC-MPS-MPA C(max) and single concentrations were weakly correlated. A limited-sampling strategy (LSS) combining C(max) and C(12h) gave satisfactory predictive performance to estimate MPA AUC(0-12h) after EC-MPS administration.For TDM in SLE patients with GFR60 ml/min/1.73 m(2), C(12h) after MMF ingestion could predict MPA AUC(0-12h), while an LSS around T(max) should be used for patients on EC-MPS.
Published: 2010
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30. Allogeneic Hematopoietic Stem-Cell Transplantation for Myeloid Sarcoma: A Retrospective Study From the SFGM-TC

Author: Didier Blaise, Patrice Chevallier, Mohamad Mohty, Nathalie Contentin, Christelle Volteau, Eric Deconinck, Mathilde Hunault, Pierre Bordigoni, Agnès Buzyn, Mauricette Michallet, Gérard Michel, Jean-Luc Harousseau, Jean-Paul Vernant, Stephane Vigouroux, Gérard Socié, Bruno Lioure, Reza Tabrizi, Saas, Philippe, 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), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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]), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]
Subjects: Male, Cancer Research, medicine.medical_treatment, Hematopoietic stem cell transplantation, Gastroenterology, 0302 clinical medicine, MESH: Child, Sarcoma, Myeloid, Child, MESH: Treatment Outcome, Cause of death, MESH: Middle Aged, Hazard ratio, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, MESH: Follow-Up Studies, Middle Aged, MESH: Transplantation, Autologous, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Sarcoma, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Survival Rate, Transplantation, Autologous, 03 medical and health sciences, Internal medicine, medicine, Myeloid sarcoma, Humans, MESH: Hematopoietic Stem Cell Transplantation, Retrospective Studies, MESH: Adolescent, MESH: Humans, business.industry, MESH: Sarcoma, Myeloid, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, MESH: Male, Surgery, Transplantation, business, MESH: Female, Follow-Up Studies, 030215 immunology
Abstract: Purpose This retrospective multicenter study assessed the outcome of 51 patients with myeloid sarcoma (MS) who underwent allogeneic hematopoietic stem-cell transplantation (alloHSCT). Patients and Methods Most patients had MS presenting in conjunction with acute myeloid leukemia (AML) or after AML. Six patients had isolated MS. The median time between diagnosis and alloHSCT was 8 months (range, 2.8 to 67). Forty patients were in complete remission (CR) at time of alloHSCT. Results With a median follow-up of 33 (range, 1 to 182) months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival were 47% (95% CI, 33% to 61%) and 36% (95% CI, 24% to 50%) at 5 years. Twenty patients (39%) relapsed at a median of 204 (range, 35 to 1151) days after alloHSCT, with relapse being the major cause of death. In a Cox multivariate analysis, age ≥ 15 years and remission status at time of alloHSCT (CR v other) were associated with improved OS (hazard ratio [HR], 0.27; 95% CI, 0.12 to 0.65; P = .003; and HR, 0.22; 95% CI, 0.08 to 0.57; P = .002, respectively). Conclusion We conclude that first-line alloHSCT performed early in the course of MS is a valid therapeutic option.
Published: 2008
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31. Is Arsenic Trioxide (ATO) Required in the Treatment of Standard Risk Newly Diagnosed APL? Analysis of a Randomized Trial (APL 2006) By the French Belgian Swiss APL Group

Author: Lionel Ades, Norbert Vey, Hervé Dombret, Xavier Thomas, Sylvie Chevret, Julie Lejeune, Agnès Guerci-Bresler, Patrice Chevallier, Arnaud Pigneux, Eric Deconinck, Dominique Bordessoule, Olivier Tournilhac, Raffoux Emmanuel, Christian Récher, Thierry Lamy, Claude Gardin, Pierre Fenaux, Stéphane de Botton, Olivier Spertini, Jean-Francois Lambert, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), CHU Pontchaillou [Rennes], 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 ), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service d'Hématologie Clinique Adulte et de Thérapie Cellulaire, Centre Hospitalier Universitaire de Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de biostatistiques et information médicale [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-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 ), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Anthracycline Antibiotics, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Newly diagnosed, Interim analysis, Biochemistry, 3. Good health, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, chemistry, law, Standard Risk, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Arsenic trioxide, business, 030215 immunology
Abstract: Background: ATO is very effective in the treatment of APL and recent results have shown that ATRA+ATO combinations (without CT) were at least as effective as classical ATRA + anthracycline based chemotherapy (CT) while being less myelosuppressive (Lo Coco, NEJM 2014, Burnett, Lancet Oncol, in press). However, access to ATO remains limited for frontline treatment of APL in most countries, which must mainly rely on ATRA+CT combination. In those combinations, investigators have suggested that the amount of CT could be reduced and the incidence of relapses further diminished by introducing ATRA (Sanz) or ATO (Powell) during consolidation cycles. In a randomized trial (APL 2006 trial), we compared for consolidation treatment (after ATRA CT induction treatment) ATO, ATRA and the "classical" Ara C in standard risk APL (ie with baseline WBC < 10G/L). Methods: Between 2006 and 2013 newly diagnosed APL patients (pts) < 70 years with WBC < 10 G/L , after an induction treatment consisting of ATRA 45mg/m2/d until CR with Idarubicin (Ida) 12 mg/m2/dx3 and AraC 200mg/m2/dx7 started on day 3, were randomized for consolidation between AraC, ATO and ATRA. The AraC group ( standard group) received a first consolidation course with, Idarubicin (Ida) 12 mg/m2/dx3 and AraC 200mg/m2/dx7, a second consolidation with Ida 9 mg/m2/dx3 and AraC 1g/m2/12h x4d, and a maintenance during two years with intermittent ATRA 15d/ 3 months and continuous 6 MP + MTX,). The ATO and ATRA groups received the same treatment as the AraC group, but AraC was replaced respectively by ATO 0.15 mg/Kg/d d1 to 25 and ATRA 45 mg/m2/d d1 to 15 for both consolidation courses. We present here results of an analysis made at the reference date January 1st 2014 in the 398 pts aged < 70 years with WBC Results: Among the 398 included pts, 7 were excluded for diagnosis error, 96% achieved CR, 12 (3%) had early death (from bleeding (n=1), sepsis (n=6), Thrombosis (n=4), cardiac arrest (n=1)) and 4 (1%) had resistant leukemia. 353 pts were randomized for consolidation (118, 118 and 117 in the AraC, ATO and ATRA arms, respectively). Pre-treatment characteristics were well balanced between the 3 consolidation groups. Overall, 4, 0, and 7 pts had relapsed (p=0.03) and 6, 5, and 5 pts (p=0.93) had died in CR in the AraC, ATO and ATRA consolidation groups, respectively. Causes of death in CR were sepsis (n=4) and hemorrhage (n=2), AML/MDS (n=5), relapse of a previous cancer (n=2), other (n=2). Two of the 6 deaths in CR related to myelosuppression occurred in each arm. Of the 5 patients who developed AML/MDS, 2, 1 and 2 had been treated in the AraC, ATO and ATRA arms, respectively. Five-year EFS from randomization was 90.8% [85.5; 96.5], 92.5% [87.6; 98.4] and 86.8% [79.7; 94.5] (p=0.52), 5y CIR was 3.89% [0.08 ; 7.69], 0% [0 ; 0], 7.41% [1.96 ; 12.87] (p=0.03) and 5 year OS was 93.6% [89.1; 98.3]%, 92.8% [87.6; 98.4]% and 91.9% [85.4; 98.9] (p=NS), in the AraC, ATO and ATRA consolidation groups, respectively. Median time to ANC >1 G/L after the first consolidation course was 24, 24 and 17 in the AraC, ATO and ATRA group, respectively (AraC vs ATO: p= 0.96; ATO vs ATRA: p1 G/L after the second consolidation course was 23, 19 and 13 days (AraC vs ATO: p= 0.02; ATO vs ATRA: p Median duration of hospitalization after the first and the second consolidation course were 32d, 29d, 32d (p= NS) and 30d, 17d, 15d in the AraC, ATO and ATRA group, respectively (p Conclusion: Very high CR rates are now obtained in standard risk APL on a very large multicenter basis using classical ATRA and anthracycline based CT combinations, with very few relapses. On the other hand, our results strongly suggest that relapse rates observed with regimens without ATO, although they are low, can be significantly further reduced by addition of ATO. The Ida-ATRA consolidation regimen in particular, while carrying reduced toxicity, was associated with a relapse rate of 7.4%. Our results therefore advocate systematic introduction of ATO in the first line treatment of standard risk APL, but probably not concomitantly with CT, a situation where we found myelosuppression to be significant. Disclosures Guerci-Bresler: ARIAD: Speakers Bureau; BMS: Speakers Bureau; Novartis: Speakers Bureau; PFIZER: Speakers Bureau. Vey:Roche: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Deconinck:NOVARTIS: Other: Travel for international congress; PFIZER: Research Funding; CHUGAI: Other: Travel for international congress; ALEXION: Other: Travel for international congress; JANSSEN: Other: Travel for international congress; ROCHE: Research Funding; LFB loboratory: Consultancy. Dombret:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux:Celgene Corporation: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.
Published: 2015

32. Addition of Lomustine (CCNU) to Induction and Post-Remission Chemotherapy for Fit Elderly AML Patients without Unfavorable Cytogenetics: Results of the Lamsa-2007 Goelams Trial

Author: Norbert Vey, Catherine Lacombe, Rachid Salmi, Jean-Yves Cahn, Mario Ojeda, Caroline Bonmati, Thibaut Leguay, Anne Banos, Marc Bernard, Isabelle Luquet, Romain Guieze, François Dreyfus, Eric Jourdan, Roselyne Delepine, Jacques Delaunay, Ariane C Mineur, Marie C. Béné, Bruno Lioure, Jean-Christophe Ianotto, Arnaud Pigneux, Hichri Yosr, Julien Asselineau, Hacene Zerazhi, Norbert Ifrah, Pascale Cornillet-Lefebvre, Christian Recher, Mathilde Hunault, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie [Tours], Hôpital Bretonneau-CHRU Tours, Service d'hématologie, Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Soutien Méthodologique à la Recherche Clinique ( USMR ), CHU Bordeaux [Bordeaux], Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I ( UdA ), Laboratoire d'hématologie, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de cancérologie et d'hématologie, Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Hôpital Morvan [Brest], Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Hôpital de Bayonne, CH de la Côte Basque, Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'hématologie clinique, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, CHU Pontchaillou [Rennes], Centre Hospitalier Saint Jean de Perpignan, 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 ), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Institut de Santé Publique, d'Epidémiologie et de Développement, Université Bordeaux Segalen - Bordeaux 2, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, 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), Unité de Soutien Méthodologique à la Recherche Clinique (USMR), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier Universitaire de Reims (CHU Reims), Ligue Nationale Contre le Cancer (LNCC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de la Côte Basque (CHCB), Université de Rennes (UR)-Hôpital Pontchaillou, 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) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, 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), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], 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), CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Population, Biochemistry, Gastroenterology, Confirmatory trial, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Medicine, Idarubicin, education, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chemotherapy, education.field_of_study, [ SDV ] Life Sciences [q-bio], business.industry, Cell Biology, Hematology, Lomustine, Chemotherapy regimen, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Cytarabine, business, medicine.drug
Abstract: Background: The treatment of Acute Myeloid Leukemia (AML) in elderly patients remains unsatisfactory, with an expected survival time of about 1 year post diagnosis. In an attempt to improve outcome for these patients, the prospective open-label phase 3 LAMSA-2007 trial (Clinicaltrial.gov ID, NCT00590837) repeated, at decreasing doses in consolidation and reinduction courses, a standard induction regimen with cytarabine and idarubicin (IC), with or without the randomized addition of lomustine (ICL). This alkylating agent with significant anti-leukemic activity is widely used in France for AML therapy. This study was performed as a confirmatory trial, following our previous report of the French experience in which this compound stood out as a favorable factor of improved outcome for patients with non-unfavorable cytogenetics (Pigneux, JCO 2010). Methods: Eligible patients were adults 60 years old or more, with previously untreated AML, fit to receive intensive chemotherapy (ECOG and SORROR Results: From February 2008 to December 2011, 459 patients were enrolled and 424 were evaluable. The median age of analyzed patients was 68 yo (60-81), 58% were male. Cytogenetics was favorable (5.2%), intermediate (90.3%) or failure (4.5%). Overall, 26% of the patients had a favorable genotype based on NPM, CEBPa and FLT3 ITD mutational status. The two arms were comparable for pre-treatment characteristics. There were 3.7% induction deaths in the IC arm and 7.7% in the ICL arm (p=0.11). The rate of primary resistant AML was 21.4% after IC versus 7.7% after ICL (p Conclusion: Thisschedule using the same drugs at decreasing doses during induction, consolidation and reinductions provided unusually good results in the IC arm, further improved in the ICL arm by the addition of lomustine, in fit elderly AML patients without unfavorable cytogenetics, with acceptable toxicity. The higher rate of CR, reduced relapse incidence and improved EFS in the ICL arm support the anti-leukemic effect of lomustine in elderly AML patients, even if it does not translate in a significantly prolonged long term overall survival. New strategies for maintenance therapy remain to be improved in this setting to sustain this positive effect. Disclosures Vey: Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria.
Published: 2015

33. Impact of HLA of Winning Cord Blood Unit on Outcomes after Double Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee Cellular Therapy and Immunobiology Working Party and the Acute Leukemia Working Party of the EBMT

Author: Nigel H. Russell, Eliane Gluckman, Dimitrios Karakasis, Annalisa Ruggeri, Gérard Socié, Eric Deconinck, Pierre-Simon Rohrlich, Mauricette Michallet, Pierre Feugier, Henrik Sengeloev, Thierry Lamy, Vanderson Rocha, Jan J. Cornelissen, Arnon Nagler, Noel-Jean Milpied, Myriam Labopin, Eefke Petersen, Charles Craddock, Didier Blaise, Federica Giannotti, Mohamad Mohty, Chantal Kenzey, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre International des greffes [CHU Saint-Antoine] (EBMT), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de pédiatrie, Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Relations Hôte-Environnement (RHEM), Université Henri Poincaré - Nancy 1 (UHP), CHU Pontchaillou [Rennes], 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 ), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), France Monacord, Centre Scientifique de Monaco (CSM), Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center at Tel hashomer, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Université de Rennes (UR)-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 )
Subjects: medicine.medical_specialty, Acute leukemia, Thymoglobulin, Umbilical Cord Blood Transplantation, business.industry, [SDV]Life Sciences [q-bio], Immunology, Retrospective cohort study, Cell Biology, Hematology, Human leukocyte antigen, medicine.disease, Biochemistry, 3. Good health, Transplantation, Leukemia, Internal medicine, Cord blood, medicine, Intensive care medicine, business
Abstract: Umbilical cord blood transplantation (UCBT) from unrelated donor is a valid alternative for patients (pts) with acute leukemia (AL) who lack an HLA matched donor. Double UCBT (dUCBT) has extended the use of UCBT to adults. In the majority of the cases, chimerism analysis shows that one unit emerges as the sole source of long term hematopoiesis in the recipient (rcp) following dUCBT. However, no clear factor has yet been identified to reliably predict which unit will emerge as the predominant one. With the aim of analyzing factors that may predict cord blood unit (CBU) predominance and the impact of the winning CBU characteristics on outcomes after dUCBT, we studied adults with AL who underwent dUCBT as first transplant between 2004 and 2013 at EBMT centres. We selected pts who achieved engraftment and who had available chimerism data assessed within day 130 after dUCBT, with one of the CBUs representing at least 50% of the rcp hematopoiesis (winCBU). According to these criteria, 347 pts were included: 323 had full donor (18 being dual chimera) and 24 had mixed chimerism (>5% of donor cells). At diagnosis, 35% had ALL and 65% AML. At dUCBT 45% were in first complete remission (CR), 44% in second CR and 11% had more advanced disease. Overall, 33% had high risk cytogenetic features. Median time from diagnosis to dUCBT was 12 months (range, 2-202), median age was 40 years (y) (18-76). Conditioning regimen (CT) was reduced intensity (RIC) in 52%. Cyclophosphamide+fludarabine+total body irradiation was the most frequent CT (63%). Anti-thymoglobulin (ATG) was administrated in 25% of the transplants. Median number of total nucleated cells (TNC) and CD34+ cells at cryopreservation were 5.1x107/Kg (range, 2.3-13.7) and 1.3x105/Kg (range, 0.4-10.7), respectively. Considering the unit with the highest number of HLA mismatches (MMs) with the rcp, 73% of the donors were matched at 4 or less loci (≤4/6). For winCBUs, median number of TNC and CD34 cells at cryopreservation were 2.5x107/Kg (range, 0.95-6) and 1x105/Kg (range, 0.06-10), respectively. Only 4% of the winCBUs were 6/6 HLA-matched to the rcp, while 37% were 5/6, 55% were 4/6 and 4% were 3/6 HLA-matched. Overall, 54% of the winCBUs were gender matched and 38% were ABO compatible with the rcp. WinCBUs median age was 3.4 years (range, 0.2-14). As for inter unit characteristics, 50% of the pts received gender matched units. Units were ABO compatible in 40% of the cases, while 30% had minor and 30% had major ABO incompatibility. In our study population, median follow-up for survivors was 35 months (range, 3-99). All pts engrafted with neutrophil >0.5x109/L in a median time of 25 days (range, 6-66) post DCBT. No secondary graft failure was reported. The cumulative incidence (CI) of acute GvHD grade II-IV at 100 days was 41% with a median time of onset of 29 days (range, 7-106). The 3y-CI of chronic GvHD was 41% (50% of the pts had extensive). The 3y-CI of relapse (RI) and transplant related mortality (TRM) were 27% and 24%, respectively. At 3y, leukemia free survival (LFS) was 49% and overall survival (OS) was 54%. In multivariate analysis (MVA) including unit characteristics (HLA and gender matching, type of HLA MMs, number of TNC and CD34 cells at cryopreservation, ABO compatibility and unit age) and inter unit features (gender match, ABO compatibility), no significant factor predicting the winCBU was identified. Analyzing the impact of winCBU on dUCBT outcomes, the HLA matching between CBU and the rcp was the only characteristic related to the winCBU significantly affecting results. The 3y-LFS for pts with 6/6 or 5/6 HLA-matched winCBUs was 56% as compared to 44% for those with 4/6 (p=0.03), while OS was 62% versus 49% (p=0.01), respectively. Acute GvHD was increased in pts receiving a 4/6 HLA-matched winCBU (46% versus 35% for those 6/6 or 5/6, p=0.04). In MVA, 4/6 HLA-matched winCBU was associated with decreased LFS (HR 1.5, p=0.03) and OS (HR 1.5, p=0.03), and with increased TRM (HR 1.9, p=0.03) and acute GvHD (HR 1.7, p=0.01). Notably, older winCBUs (>3.4y) were associated with higher acute GvHD (48% versus 35%; HR 1.6, p=0.02). Other factors associated with poor outcomes were advanced disease status and the use of ATG. Although we failed to identified any factor predicting CBU predominance, we were able to demonstrate that a 4/6 HLA matched winCBU is associated with poor outcomes. Therefore, selecting units with lower number of HLA MMs for dUCBT may improve final outcomes. Disclosures Russell: Therakos: Other: shares. Mohty:Riemser: Honoraria, Research Funding. Nagler:Biokine LTD: Consultancy.
Published: 2015
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34. Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group

Author: Thorsten, Braun, Sophie, Cereja, Sylvie, Chevret, Emmanuel, Raffoux, Marie, Beaumont, Laurence, Detourmignies, Arnaud, Pigneux, Xavier, Thomas, Dominique, Bordessoule, Agnès, Guerci, Thierry, Lamy, Christian, Recher, Xavier, Poiré, Olivier, Tournilhac, Olivier, Spertini, Christine, Chomienne, Laurent, Degos, Hervé, Dombret, Lionel, Adès, Pierre, Fenaux, Norbert, Vey, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique, Centre Hospitalier de Roubaix, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-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 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 Clinique Adulte et de Thérapie Cellulaire, CHU Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Unite de Biologie Cellulaire, Hématologie -Immunologie -Cibles thérapeutiques, Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), 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, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Jonchère, Laurent
Subjects: Adult, Male, Incidence, [SDV]Life Sciences [q-bio], Chemoradiotherapy, Middle Aged, acute promyelocytic leukemia, prostate cancer, [SDV] Life Sciences [q-bio], Belgium, Leukemia, Promyelocytic, Acute, Recurrence, immune system diseases, Antineoplastic Combined Chemotherapy Protocols, Breast Cancer, Humans, Anthracyclines, Female, secondary acute myeloid leukemia, France, Prospective Studies, Mitoxantrone, neoplasms, Switzerland, Aged
Abstract: International audience; Background - Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL.Methods - The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL.Results - In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P Conclusions - Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL.
Published: 2015
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35. Reconstitution of Natural Killer Cells in HLA-Matched HSCT after Reduced-Intensity Conditioning: Impact on Clinical Outcome

Author: Roberto Crocchiolo, Christian Chabannon, Caroline Pical-Izard, Christophe Picard, Coralie Frassati, Sylvaine Just-Landi, Daniel Olive, Didier Blaise, Eloïse Kochbati, Samuel Granjeaud, Cyril Fauriat, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Hematology and BMT Unit, Hematology and BMT Unit, Unit of Lymphoid Malignancies, Department of Oncology, Biostatistics Unit, Università degli studi di Genova = University of Genoa (UniGe), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], University of Genoa (UNIGE), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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)-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 Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]
Subjects: Transplantation, NK functions, Lymphokine-activated killer cell, HLA-matched, Cell growth, business.industry, medicine.medical_treatment, Degranulation, Stem cell transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Human leukocyte antigen, Hematopoietic stem cell transplantation, Hematology, NK cells, 3. Good health, Reduced-intensity conditioning, Interleukin 21, Immune system, Cytokine, hemic and lymphatic diseases, Immunology, Medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Recent advances in the development of reduced-intensity conditioning (RIC) have allowed a broader range of patients to access allogeneic hematopoietic stem cell transplantation (HSCT). Reconstitution of an effective immune system post-transplant, including natural killer (NK) cells, is critical for both tumor control and infectious disease control or prevention. The development and functions of NK cells in such settings remain elusive. Here we analyzed NK cell development in HLA-matched HSCT from related or unrelated donors, after RIC that included antithymocyte globulin (N = 45 patients). Our data reveal that NK cells quickly recover after RIC-HSCT, irrespective of donor type. Rapidly re-emerging NK cells, however, remain immature for more than 6 months. Effector functions resemble that of immature NK cells because they poorly produce IFN-γ and TNF-α in response to target cell stimulation, despite a rapid acquisition of degranulation ability and MIP-1β production. Strikingly, rapid reconstitution of cytokine production correlates with a lower relapse incidence (P = .01) and a better survival rate (P
Published: 2015
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36. Once-daily prolonged release tacrolimus in liver transplantation: Experts' literature review and recommendations

Author: Olivier Guillaud, Pauline Houssel-Debry, Audrey Coilly, Faiza Chermak, Christophe Duvoux, Martine Neau-Cransac, Yvon Calmus, Jérôme Dumortier, Jeanick Stocco, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies du foie, Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Jonchère, Laurent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies du foie [CHU Rennes], and Centre Hospitalier Universitaire [Rennes]
Subjects: Graft Rejection, medicine.medical_specialty, Time Factors, Dose, Chemistry, Pharmaceutical, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Urology, Context (language use), 030230 surgery, Liver transplantation, Pharmacology, Drug Administration Schedule, Tacrolimus, Medication Adherence, Food-Drug Interactions, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Transplantation, Hepatology, medicine.diagnostic_test, business.industry, Graft Survival, Area under the curve, Liver Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], stomatognathic diseases, Treatment Outcome, Therapeutic drug monitoring, Delayed-Action Preparations, Concomitant, Practice Guidelines as Topic, Trough level, 030211 gastroenterology & hepatology, Surgery, Drug Monitoring, business, Immunosuppressive Agents
Abstract: International audience; The efficacy and safety of tacrolimus (Tac) twice daily (bid) and once a day (qd) formulations are considered to be similar. However, the available information regarding initiation of Tac qd is sparse, and practical information is lacking. On the basis of a literature review, clinical efficacy, and safety trials, French experts in the liver transplantation field were asked to highlight pharmacokinetic (PK) differences between both formulations to assess efficacy and safety of the qd formulation in the context of de novo initiation or conversion and to provide their recommendations for initiation and day-to-day management of Tac qd. The same efficacy and safety profile is found for both immediate-release and prolonged-release Tac. PK differences carry on absorption because of the difference in formulations but not on metabolism or excretion. Tac qd offers a better reproducibility in exposure than Tac bid but is associated with an increased risk of disturbed absorption in case of a change in intestinal motility. The same therapeutic drug monitoring with Tac qd and bid could be applied, based on minimal concentration (trough level; Cmin ), as there is a similar strong correlation between Cmin and the area under the curve (AUC) for both formulations. Different protocols for Tac qd initiation were described through numerous studies, except for early conversion: initiation on day 0, using 0.10 to 0.20 mg/kg/day as monotherapy, or lower dosages in case of concomitant immunosuppressant treatment or poor graft quality; early conversion from day 5 to 6 months, preferably before hospital discharge, using a 1 to 1.3 mg/kg/day schedule and with first Cmin assessment 48 hours after the conversion; and later conversion (\textgreater6 months posttransplantation) using a milligram-to-milligram dosage schedule, and with dose adjustment based on weekly Cmin measurement. Experts underline that an increase in treatment adherence was expected using Tac qd in liver recipients. In conclusion, Tac qd has the same efficacy and safety profile as Tac bid. De novo introduction or later conversion are well documented but could differ from day-to-day practice. Liver Transpl 21:1312-1321, 2015. © 2015 AASLD
Published: 2015
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37. A bilayer model of human atria: mathematical background, construction, and assessment

Author: Pierre Jaïs, Simon Labarthe, Jason D. Bayer, Yves Coudière, Jacques Henry, Hubert Cochet, Edward J. Vigmond, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], PlaFRIM (https://plafrim.bordeaux.inria.fr/doku.php), ANR-10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), ANR-13-MONU-0004,HR-CEM,Modèles numériques haute résolution de l'électrophysiologie cardiaque(2013), European Project: 261057,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUTRAF(2010), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], ANR-10-IAHU-04/10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest
Subjects: Surface (mathematics), surface model, Action Potentials, atrial arrhythmia, Atrial Function, Right, 030204 cardiovascular system & hematology, Right atrial, Pectinate muscles, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Monolayer, medicine, Humans, Computer Simulation, Heart Atria, 030304 developmental biology, 0303 health sciences, human atria, two-layer model, business.industry, Bilayer, Models, Cardiovascular, Arrhythmias, Cardiac, Numerical Analysis, Computer-Assisted, Atrial Remodeling, Anatomy, atrial physiology, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Coupling (electronics), Kinetics, medicine.anatomical_structure, Atrial Function, Left, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, Crista terminalis, business, Biological system, Coupling coefficient of resonators
Abstract: International audience; (1) Aims: Atrial numerical modelling has generally represented the organ as either a surface or tissue with thickness. While surface models have significant computational advantages over tissue models, they cannot fully capture propagation patterns seen in vivo, such as dissociation of activity between endo-and epicardium. We introduce an intermediate representation, a bilayer model of the human atria, which is capable of recreating recorded activation patterns. (2) Methods: We simultaneously solved two surface monodomain problems by formalizing an optimization method to set a coupling coefficient between them. Two different asymptotically equivalent numerical implementations of the model are presented. We then built a geometrically and electrophysiologically detailed model of the human atria based on CT data, including two layers of fibre directions, major muscle bundles, and discrete atrial coupling. We adjusted parameters to recreate clinically measured activation times. Activation was compared to a monolayer model. (3) Results: Activation was fit to the physiological range measured over the entire atria. The crista terminalis and pectinate muscles were important for local right atrial activation, but did not significantly affect total activation time. Propagation in the bilayer model was similar to that of a monolayer, but with noticeable difference, due to three-dimensional propagationwhere fibre direction changed abruptly across the wall, resulting in a slight dissociation of activity. (4) Conclusion: Atrial structure plays the dominant role in determining activation. A bilayer model is able to take into account transmural heterogeneities, while maintaining thelow computational load associated with surface models.
Published: 2014
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38. An Iterative method for solving the inverse problem in Electrocardiography imaging: From body surface to heart potential

Author: Nejib Zemzemi, Bourenane, H., Cochet, H., Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], MIT, Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: [SDV]Life Sciences [q-bio], [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: International audience; Solving the inverse problem in electrocardiogra- phy imaging (ECGI) is a challenging problem. In this work, we present an ECGI solver based on the iterative Kozlov- Maz'ya-Fomin (KMF) method. Because of the lack of gold standards data for this problem, we propose to test this method on synthetical data generated based on the bidomain state-of- the-art model. We segmented a real geometry of a 43 years old women and produced a computational geometry on which we run the forward problem body surface potentials BSPs. We analyse the reconstructed solution using the Relative error in time and space, the correlation coefficient and phase mapping procedure.
Published: 2014

39. Impact of Neoadjuvant Chemoradiotherapy on Postoperative Outcomes After Esophageal Cancer Resection

Author: Gronnier, Caroline, Tréchot, Boris, Duhamel, Alain, Mabrut, Jean-Yves, Bail, Jean-Pierre, Carrère, Nicolas, Lefevre, Jérémie, Brigand, Cécile, Vaillant, Christophe, Adham, Mustapha, Msika, Simon, Demartines, Nicolas, El Nakadi, Issam, Piessen, Guillaume, Meunier, B., Collet, Denis, Mariette, Christophe, Luc, G., Cabau, Magalie, Jougon, Jacques, Badic, Bogdan, Lozach, Patrick, Cappeliez, Serge, Lebreton, G., Alves, A., Flamein, Renaud, Pezet, Denis, Pipitone, Federica, Contival, Nicolas, Pappalardo, Eric, Mantziari, Styliani, Hec, F., Vanderbeken, Marguerite, Tessier, Williams, Briez, Nicolas, Fredon, F, Gainant, Alain, Mathonnet, Muriel, Bigourdan, Jm, Mezoughi, Salim, Ducerf, C., Baulieux, Jacques, Pasquer, Arnaud, Baraket, Oussama, Poncet, Gilles, Vaudoyer, Delphine, Enfer, J, Villeneuve, L, Glehen, O., Coste, T, Fabre, J.M, Marchal, F, Frisoni, Romain, Ayav, Ahmet, Brunaud, Laurent, Bresler, Laurent, Cohen, C, Aze, Olivier, Vénissac, Nicolas, Pop, D., Mouroux, J, Donici, Ion, Prudhomme, M., Felli, E., Lisunfui, Stéphanie, Seman, Marie, Petit, Gaelle Godiris, Karoui, M, Tresallet, Christophe, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service d'Hématologie [CHU Huriez Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Université Lille Nord de France (COMUE), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de biostatistiques [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de chirurgie digestive, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Pontchaillou [Rennes], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], CIC-IT Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de chirurgie générale et viscérale, Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Clermont-Ferrand, Service Chirurgie Digestive, Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Alimentary Tract Surgery, University Hospital, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Service de Chirurgie Digestive Hépatobiliaire et Endocrine [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), Department of Thoracic Surgery, Louis Pasteur Hospital, Service de Chirurgie Générale, Viscérale et Endocrinienne [CHU Pitié-Sapêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Biostatistiques [CHRU Lille], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Objectives: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection.Background: Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL.Methods: Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n = 593) were compared with those treated by primary surgery (n = 1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics.Results: Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P = 0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P = 0.110) and 33.4% versus 32.1% (P = 0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P = 0.291), whereas chylothorax (2.5% vs 1.2%; P = 0.020), cardiovascular complications (8.6% vs 0.1%; P = 0.037), and thromboembolic events (8.6% vs 6.0%; P = 0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P = 0.228), with more chylothorax (2.5% vs 0.7%; P = 0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P = 0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT.Conclusions: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).
Published: 2014
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40. Confidence-based Training for Clinical Data Uncertainty in Image-based Prediction of Cardiac Ablation Targets

Author: Nicholas Ayache, Hubert Cochet, Loic Le Folgoc, Benjamin Berte, Maxime Sermesant, Jatin Relan, Jan Margeta, Michel Haïssaguerre, Pierre Jaïs, Yuki Komatsu, Rocio Cabrera-Lozoya, Cabrera Lozoya, Rocio, Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Hôpital Haut-Lévêque, and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Engineering, business.industry, 0206 medical engineering, Training (meteorology), Process (computing), [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Sudden cardiac arrest, 02 engineering and technology, Cardiac Ablation, Sensor fusion, Machine learning, computer.software_genre, 020601 biomedical engineering, Image (mathematics), Random forest, 0202 electrical engineering, electronic engineering, information engineering, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, 020201 artificial intelligence & image processing, Computer vision, Artificial intelligence, medicine.symptom, business, computer, Image based
Abstract: International audience; Ventricular radio-frequency ablation (RFA) can have a critical impact on preventing sudden cardiac arrest but is challenging due to a highly complex arrhythmogenic substrate. This work aims to identify local image characteristics capable of predicting the presence of local abnormal ventricular activities (LAVA). This can allow, pre-operatively and non-invasively, to improve and accelerate the procedure. To achieve this, intensity and texture-based local image features are computed and random forests are used for classification. However using machine-learning approaches on such complex multimodal data can prove difficult due to the inherent errors in the training set. In this manuscript we present a detailed analysis of these error sources due in particular to catheter motion and the data fusion process. We derived a principled analysis of confidence impact on classification. Moreover, we demonstrate how formal integration of these uncertainties in the training process improves the algorithm's performance, opening up possibilities for non-invasive image-based prediction of RFA targets.
Published: 2014

41. Influence of Transmural Slow-Conduction Zones on the Long- Time Behaviour Of Atrial Arrhythmia. A Numerical Study with a Human Bilayer Atrial Model

Author: Simon Labarthe, Edward Vigmond, Yves Coudière, Jacques Henry, Hubert Cochet, Pierre Jais, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], plafrim, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: cardiovascular system, cardiovascular diseases, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: International audience; Atrial fibrosis is known to be a factor in the perpetu ation of atrial arrhythmia. Despite the thinness of atrial tissue, the fibrosis distribution may not be homogeneous through the entire thickness of the atria. This study aims to elucidate the respective influences of a transmural and a non-transmural distribution of fibrosis, described as a slow conduction zone, on the perpetuation of an arrhythmic episode, compared to a control situation. We used a bilayer monodomain representation of the atria that included transmural heterogeneities of fibre organisation. This model allowed long simulations for a sustainable computational load. We observed that when the fibrosis was transmural, the centre of the rotor was anchored in the slow conduction zone and was stable during a 10 seconds simulation, whereas the other simulations showed meandering rotors that disappeared after a few seconds. This study provided insight into the influence of transmural fibrosis on atrial arrhythmia perpetuation. In our model framework, only a transmural fibrosis distribution had a stabilizing effect on reentrant circuits. The bilayer model proved to be a good trade-off between accuracy and speed for observing the influence of transmural heterogeneities on atrial arrhythmia over long periods.
Published: 2013

42. A Bilayer Representation of the Human Atria

Author: Simon Labarthe, Yves Coudière, Jacques Henry, Pierre Jaïs, Hubert Cochet, Edward J. Vigmond, Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], EMBS, plafrim, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Time Factors, Materials science, medicine.medical_treatment, Finite Element Analysis, Shell (structure), Action Potentials, Catheter ablation, 030204 cardiovascular system & hematology, Pectinate muscles, 03 medical and health sciences, 0302 clinical medicine, Multidetector Computed Tomography, medicine, Humans, Computer Simulation, Heart Atria, 030304 developmental biology, Fibrillation, Double layer (biology), 0303 health sciences, Orientation (computer vision), Models, Cardiovascular, Reproducibility of Results, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, medicine.anatomical_structure, Mesh generation, medicine.symptom, Crista terminalis, Biomedical engineering
Abstract: International audience; Atrial fibrillation is the most commonly encountered clinical arrhythmia. Despite recent advances in treatment by catheter ablation, its origin is still incompletely understood and it may be difficult to treat. Computer modelling offers an attractive complement to experiment. Simulations of fibrillation, however, are computationally demanding since the phenomenon requires long periods of observation. Because the atria are thin walled structures, they are often modelled as surfaces. However, this may not always be appropriate as the crista terminalis and pectinate muscles are discrete fibrous structures lying on the endocardium and cannot be incorporated into the surface. In the left atrium, there are essentially two layers with an abrupt change in fibre orientation between them. We propose a double layer method, using shell elements to incorporate wall thickness, where fibre direction is independent in each layer and layers are electrically linked. Starting from human multi- detector CT (MDCT) images, we extracted surfaces for the atria and manually added a coronary sinus. Propagation of electrical activity was modelled with the monodomain equation. Results indicate that major features are retained while reducing computation cost considerably. Meshes based on the two layer approach will facilitate studies of AF.
Published: 2013
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43. Surface-based electrophysiology modeling and assessment of physiological simulations in atria

Author: Michel Haïssaguerre, Dominique Chapelle, Jean-Frédéric Gerbeau, Annabelle Collin, Mélèze Hocini, Mathematical and Mechanical Modeling with Data Interaction in Simulations for Medicine (M3DISIM), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Numerical simulation of biological flows (REO), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Inria Paris-Rocquencourt, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Sébastien Ourselin and Daniel Rueckert and Nicolas Smith, École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Surface (mathematics), Materials science, Asymptotic analysis, Left atrium, Bidomain model, Cardiology, 3d model, 030204 cardiovascular system & hematology, 01 natural sciences, 010101 applied mathematics, 03 medical and health sciences, Electrophysiology, 0302 clinical medicine, medicine.anatomical_structure, Electrophysiology modelling, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, 0101 mathematics, Wall thickness, Anisotropy, Biological system, Simulation
Abstract: International audience; The objective of this paper is to assess a previously-proposed surface-based electrophysiology model with detailed atrial simulations. This model - derived and substantiated by mathematical arguments - is specifically designed to address thin structures such as atria, and to take into account strong anisotropy effects related to fiber directions with possibly rapid variations across the wall thickness. The simulation results are in excellent adequacy with previous studies, and confirm the importance of anisotropy effects and variations thereof. Furthermore, this surface-based model provides dramatic computational benefits over 3D models with preserved accuracy.
Published: 2013
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44. Double umbilical cord blood transplantation for hematological malignancies: a long-term analysis from the SFGM-TC registry

Author: Anne Sirvent, Vanderson Rocha, Reza Tabrizi, Thierry Lamy, Stephane Morisset, Gérard Socié, Gérard Michel, Marie-Lorraine Balere, Nicole Raus, Evelyne Marry, Pierre Bordigoni, Sabine Furst, Bruno Lioure, Mauricette Michallet, Bernard Rio, Nathalie Dhedin, Didier Blaise, Sébastien Maury, Eliane Gluckman, Eric Deconinck, Mohamad Mohty, Ibrahim Yakoub-Agha, Natacha Maillard, Jean-Yves Cahn, Mohamad Sobh, Jacques-Olivier Bay, Nathalie Fegueux, Agnes Buzyn, Aline Schmidt-Tanguy, Marc Renaud, Marie Robin, Hélène Labussière Wallet, Federico Garnier, Loic Fouillard, Anne Huynh, Noel Milpied, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Unité de Transplantation Médullaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital d'enfants, Département d'Hématologie et Oncologie Médicale, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, CRLCC Jean Perrin, 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], 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'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Agence de la biomédecine [Saint-Denis la Plaine], Clinical Research Unit, Haematology, CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], 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 Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Hematology, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, 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), Université de Rennes (UR)-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 ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -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 Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Hôpital d'enfants, Assistance publique - Hôpitaux de Paris (AP-HP), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Hôpital Jean Bernard, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Hematology, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-CHU Grenoble, Université Toulouse III - Paul Sabatier ( UPS ), 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 ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Hematology
Subjects: Male, Cancer Research, Time Factors, Transplantation Conditioning, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Umbilical cord, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Recurrence, Medicine, Cumulative incidence, Registries, 0303 health sciences, Hematology, Middle Aged, 3. Good health, Survival Rate, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Reduced Intensity Conditioning, Hematologic Neoplasms, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Cord, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, Genetics, Humans, Transplantation, Homologous, Molecular Biology, 030304 developmental biology, Aged, Retrospective Studies, business.industry, Umbilical Cord Blood Transplantation, Cell Biology, Neutrophil recovery, Surgery, Transplantation, business, Follow-Up Studies
Abstract: Allogeneic hematopoietic stem cell (HSC) transplantation is a curative treatment for many hematologic malignancies for which umbilical cord blood (UCB) represents an alternative source of HSCs. To overcome the low cellularity of one UCB unit, double UCB transplantation (dUCBT) has been developed in adults. We have analyzed the outcome of 136 patients who underwent dUCBT reported to the SFGM-TC registry between 2005 and 2007. Forty-six patients received myeloablative regimens, and 90 patients received reduced-intensity conditioning regimens. There were 84 cases of leukemia, 17 cases of non-Hodgkin lymphoma, 11 cases of myeloma, and 24 other hematologic malignancies. At transplantation, 40 (29%) patients were in complete remission. At day 60 after transplantation, the cumulative incidence of neutrophil recovery was 91%. We observed one UCB unit domination in 88% of cases. The cumulative incidence of day 100 acute graft-versus-host disease, chronic graft-versus-host disease, transplant-related mortality, and relapse at 2 years were 36%, 23%, 27%, and 28% respectively. After a median follow-up of 49.5 months, the 3-year probabilities of overall and progression-free survival were 41% and 35%, respectively, with a significant overall survival advantage when male cord engrafted male recipients. We obtained a long-term plateau among patients in complete remission, which makes dUCBT a promising treatment strategy for these patients.
Published: 2013
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45. A computational bilayer surface model of human atria

Author: Yves Coudière, Jacques Henry, Pierre Jaïs, Edward J. Vigmond, Hubert Cochet, Simon Labarthe, Université de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], SIgnals and SYstems in PHysiology & Engineering (SISYPHE), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Sébastien Ourselin, Daniel Rueckert, Nicolas Smith, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], S.Ourselin, D.Ruecker, N.Smith, plafrim, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and ProdInra, Archive Ouverte
Subjects: Volumetric model, Materials science, conduction, [SDV]Life Sciences [q-bio], 0206 medical engineering, computer-model, Left atrium, 02 engineering and technology, 030204 cardiovascular system & hematology, dissociation, 03 medical and health sciences, 0302 clinical medicine, Optics, Monolayer, medicine, epicardial electrical, business.industry, Bilayer, Mechanics, Thermal conduction, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 020601 biomedical engineering, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Slab, Right atrium, business
Abstract: International audience; A bilayer surface model of human atria is presented. A rule-based bi-layer physiological fibre arrangement is defined on an imaged in-vivo atrial geometry. This fibre architecture includes the main structures of fibres in the right and left atria, including the main transmural heterogeneities and transseptal connexions. The precision of the corresponding bilayer mathematical model is assessed by comparing the case of two sheets of orthogonal fibres to a three dimensional slab of tissue. A comparison of bilayer and monolayer simulations of sinus propagation is finally proposed. This model allows inclusion of transmural heterogeneities while maintaining small computational costs associated with surface models. It then proposes a good trade-off between model precision and computing efforts for performing complex atrial simulations for a clinical use.
Published: 2013
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46. Left ventricular endocardial or triventricular pacing to optimize cardiac resynchronization therapy in a chronic canine model of ischemic heart failure

Author: Pierre Jaïs, Daniel Gras, Ping Yang, Philippe Ritter, Christophe Leclercq, Pierre Bordachar, John M. Morgan, Nathan A. Grenz, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Medtronic, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, MESH: Cardiac Resynchronization Therapy, Physiology, medicine.medical_treatment, Bundle-Branch Block, Cardiac resynchronization therapy, Myocardial Ischemia, MESH: Cardiac Pacing, Artificial, 030204 cardiovascular system & hematology, Cardiac Resynchronization Therapy, MESH: Dogs, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Dogs, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, MESH: Ventricular Dysfunction, Left, medicine, Animals, MESH: Animals, MESH: Treatment Outcome, Heart Failure, MESH: Bundle-Branch Block, MESH: Catheter Ablation, business.industry, MESH: Chronic Disease, Cardiac Pacing, Artificial, medicine.disease, 3. Good health, Disease Models, Animal, Treatment Outcome, Heart failure, Anesthesia, Chronic Disease, MESH: Heart Failure, Cardiology, Catheter Ablation, MESH: Myocardial Ischemia, [SDV.IB]Life Sciences [q-bio]/Bioengineering, MESH: Disease Models, Animal, Cardiology and Cardiovascular Medicine, Ischemic heart, business, Canine model, 030217 neurology & neurosurgery
Abstract: Cardiac resynchronization therapy (CRT) is a proven treatment for heart failure but ∼30% of patients appear to not benefit from the therapy. Left ventricular (LV) endocardial and multisite epicardial [triventricular (TriV)] pacing have been proposed as alternatives to traditional LV transvenous epicardial pacing, but no study has directly compared the hemodynamic effects of these approaches. Left bundle branch block ablation and repeated microembolizations were performed in dogs to induce electrical dysynchrony and to reduce LV ejection fraction to max and other hemodynamic indexes were measured with a conductance catheter during LV epicardial, LV endocardial, biventricular (BiV) epicardial, BiV endocardial, and TriV pacing performed at three atrioventricular delays. LV endocardial pacing was obtained with a clinically available pacing system. The optimal site was defined as the site that increased dP/d tmax by the largest percentage. Implantation of the endocardial lead was feasible in all canines ( n = 8) without increased mitral regurgitation seen with transesophageal echocardiography and with full access to the different LV endocardial pacing sites. BiV endocardial pacing increased dP/d tmax more than BiV epicardial and TriV pacing on average ( P < 0.01) and at the optimal site ( P < 0.01). There were no significant differences between BiV epicardial and TriV pacing. BiV endocardial pacing was superior to BiV epicardial and to TriV pacing in terms of acute hemodynamic response. Further investigation is needed to confirm the chronic benefit of this approach in humans.
Published: 2012
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47. Past, present and future of cardiac resynchronization

Author: Philippe Ritter, Serge Cazeau, Claude Daubert, Christophe Leclercq, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Département de Rythmologie-Stimulation- Hôpital Saint-Joseph, Paris (Département de Rythmologie-Stimulation), Groupe Hospitalier Paris Saint-Joseph, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Groupe Hospitalier Paris Saint-Joseph (hpsj), and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Adult, Male, medicine.medical_specialty, Cardiac dyssynchrony, medicine.medical_treatment, Treatment outcome, Cardiac resynchronization therapy, Stimulation cardiaque, 030204 cardiovascular system & hematology, History, 21st Century, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Conduction System, Internal medicine, medicine, Animals, Humans, Cardiac Resynchronization Therapy Devices, 030212 general & internal medicine, Intensive care medicine, Ventricular dyssynchrony, Cardiac stimulation, Resynchronisation cardiaque, business.industry, Hemodynamics, Arrhythmias, Cardiac, Equipment Design, General Medicine, History, 20th Century, Middle Aged, medicine.disease, Insuffisance cardiaque, Treatment Outcome, Désynchronisation cardiaque, Clinical evidence, Cardiac resynchronization, Cardiology, cardiovascular system, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Pacemakers, Cardiology and Cardiovascular Medicine, business, Clinical evaluation, Forecasting
Abstract: International audience; The growing interest in dyssynchrony and cardiac resynchronization therapy has opened the field of cardiac stimulation to new haemodynamic indications. French investigators have played a key role in the formulation of new concepts, all arising from clinical observations, and the development (in collaboration with industry) and clinical evaluation of resynchronization devices. This review summarizes recent knowledge and perspectives pertaining to atrial, atrioventricular and ventricular dyssynchrony and resynchronization. Some of these concepts have been validated by robust clinical evidence, on the basis of which scientific recommendations have been formulated. Other concepts have been less successful but probably merit further attention.
Published: 2012
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48. Microcanonical processing methodology for ECG and intracardial potential: application to atrial fibrillation

Author: Pont, Oriol, Haïssaguerre, Michel, Yahia, Hussein, Derval, Nicolas, Hocini, Mélèze, Pont, Oriol, Geometry and Statistics in acquisition data (GeoStat), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], and CHU Bordeaux [Bordeaux]
Subjects: [PHYS.COND.CM-SM] Physics [physics]/Condensed Matter [cond-mat]/Statistical Mechanics [cond-mat.stat-mech], [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Statistical Mechanics (cond-mat.stat-mech), Physics - Data Analysis, Statistics and Probability, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], FOS: Physical sciences, Medical Physics (physics.med-ph), [PHYS.COND.CM-SM]Physics [physics]/Condensed Matter [cond-mat]/Statistical Mechanics [cond-mat.stat-mech], Physics - Medical Physics, Data Analysis, Statistics and Probability (physics.data-an), Condensed Matter - Statistical Mechanics
Abstract: Cardiac diseases are the principal cause of human morbidity and mortality in the western world. The electric potential of the heart is a highly complex signal emerging as a result of nontrivial flow conduction, hierarchical structuring and multiple regulation mechanisms. Its proper accurate analysis becomes of crucial importance in order to detect and treat arrhythmias or other abnormal dynamics that could lead to life-threatening conditions. To achieve this, advanced nonlinear processing methods are needed: one example here is the case of recent advances in the Microcanonical Multiscale Formalism. The aim of the present paper is to recapitulate those advances and extend the analyses performed, specially looking at the case of atrial fibrillation. We show that both ECG and intracardial potential signals can be described in a model-free way as a fast dynamics combined with a slow dynamics. Sharp differences in the key parameters of the fast dynamics appear in different regimes of transition between atrial fibrillation and healthy cases. Therefore, this type of analysis could be used for automated early warning, also in the treatment of atrial fibrillation particularly to guide radiofrequency ablation procedures., Transactions on Mass-Data Analysis of Images and Signals 4, 1 (2012). Accepted
Published: 2012

49. Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study

Author: Bruno Lioure, Odile Blanchet, Christian Berthou, Mario Ojeda-Uribe, Jean-Luc Harousseau, Didier Bouscary, Martin Carre, Marie C. Béné, Fabrice Larosa, Mathilde Hunault, Isabelle Luquet, Luc Fornecker, Patrice Chevallier, Brigitte Witz, Norbert Ifrah, Didier Blaise, Pascale Cornillet-Lefebvre, Thierry Lamy, Jérôme Cornillon, Anne Huynh, Martine Delain, Arnaud Pigneux, Edouard Randriamalala, Nathalie Fegueux, Jean-Yves Cahn, Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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], Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire d'hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 ), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), 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), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-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 ), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Remission Induction, Transplantation Conditioning, Myeloid, medicine.medical_treatment, Graft vs Host Disease, Kaplan-Meier Estimate, Hematopoietic stem cell transplantation, MESH: Peripheral Blood Stem Cell Transplantation, Biochemistry, MESH: Proportional Hazards Models, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Cumulative incidence, MESH: Incidence, MESH: Bone Marrow Transplantation, Bone Marrow Transplantation, MESH: Transplantation Conditioning, MESH: Middle Aged, Incidence, Incidence (epidemiology), Remission Induction, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, MESH: Antineoplastic Combined Chemotherapy Protocols, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, MESH: Leukemia, Myeloid, Acute, medicine.medical_specialty, Immunology, MESH: Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, MESH: Hematopoietic Stem Cell Transplantation, MESH: Kaplan-Meier Estimate, Proportional Hazards Models, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, Proportional hazards model, Siblings, Cell Biology, medicine.disease, Confidence interval, MESH: Male, Surgery, MESH: Siblings, Transplantation, business, MESH: Female, 030215 immunology
Abstract: The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients. This study was registered at clinicaltrials.gov as no. NCT01015196.
Published: 2012
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50. Targeting natural killer cells and natural killer T cells in cancer

Author: Didier Blaise, Christian Chabannon, Sophie Ugolini, Eric Vivier, Laurent Brossay, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre de Ressources Biologiques en Oncologie, Department of Molecular Microbiology and Immunology, Brown University, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: History, Cell type, chemical and pharmacologic phenomena, Biology, Article, Education, Immunological synapse, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Immune system, Neoplasms, Animals, Humans, 030304 developmental biology, 0303 health sciences, Lymphokine-activated killer cell, Hematopoietic Stem Cell Transplantation, Natural killer T cell, 3. Good health, Computer Science Applications, Killer Cells, Natural, Immunization, Immunology, Interleukin 12, Natural Killer T-Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030215 immunology
Abstract: International audience; Natural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.
Published: 2012
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