Search

Your search keyword '"Flore Sicre de Fontbrune"' showing total 14 results
Start Over Author "Flore Sicre de Fontbrune" Publisher hal ccsd
14 results on '"Flore Sicre de Fontbrune"'

1. Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia

Author

Marie Sebert, Stéphanie Gachet, Thierry Leblanc, Alix Rousseau, Olivier Bluteau, Rathana Kim, Raouf Ben Abdelali, Flore Sicre de Fontbrune, Loïc Maillard, Carèle Fedronie, Valentine Murigneux, Léa Bellenger, Naira Naouar, Samuel Quentin, Lucie Hernandez, Nadia Vasquez, Mélanie Da Costa, Pedro H. Prata, Lise Larcher, Marie de Tersant, Matthieu Duchmann, Anna Raimbault, Franck Trimoreau, Odile Fenneteau, Wendy Cuccuini, Nathalie Gachard, Nathalie Auger, Giulia Tueur, Maud Blanluet, Claude Gazin, Michèle Souyri, Francina Langa Vives, Aaron Mendez-Bermudez, Hélène Lapillonne, Etienne Lengline, Emmanuel Raffoux, Pierre Fenaux, Lionel Adès, Edouard Forcade, Charlotte Jubert, Carine Domenech, Marion Strullu, Bénédicte Bruno, Nimrod Buchbinder, Caroline Thomas, Arnaud Petit, Guy Leverger, Gérard Michel, Marina Cavazzana, Eliane Gluckman, Yves Bertrand, Nicolas Boissel, André Baruchel, Jean-Hugues Dalle, Emmanuelle Clappier, Eric Gilson, Ludovic Deriano, Sylvie Chevret, François Sigaux, Gérard Socié, Dominique Stoppa-Lyonnet, Hugues de Thé, Christophe Antoniewski, Dominique Bluteau, Régis Peffault de Latour, Jean Soulier, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), AP-HP Hôpital universitaire Robert-Debré [Paris], Recherche clinique appliquée à l'hématologie (URP_3518), Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Institut Gustave Roussy (IGR), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Institut Pasteur [Paris] (IP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux universitaires Est parisien [AP-HP], CHU Bordeaux [Bordeaux], 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CIC NECKER BT (CIC 1416), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Collège de France (CdF (institution)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), This study received support from the European Research Council (ERC) Consolidator Grant to J.S. (CEVAL-311660), the FP7 Eurofancolen program (HEALTH-F5-2012-305421), the ANR program PACRI (Projet alliance parisienne des instituts de recherche en cancérologie), the CONECT-AML (Collaborative Network for Children and Teenagers with Acute Myeloid Leukemia) program supported by a grant from the Institut National du Cancer (INCa), Fondation ARC, Ligue nationale contre le cancer, and Laurette Fugain (INCa-ARC-LIGUE_11905) to J.S. and C.A., and the Association Française pour la Maladie de Fanconi (AFMF) grants 'Histoire naturelle de la maladie de Fanconi' to R.P.L. and J.S., 'Modélisation de la transformation leucémique dans la maladie de Fanconi' to D.B., and 'Cribles fonctionnels à haut débit de gènes modificateurs de la maladie de Fanconi' to C.G. M.S. was supported by the AVIESAN-INCa Program 'Formation à la Recherche Translationnelle,' and A.R. by a grant from the Fondation ARC. The work in E.G.’s lab is supported by Fondation ARC and ANR Telochrom. The work in L.D.’s lab is supported by INCa (PLBIO16-181) and ERC (310917)., ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011), European Project: 311660,EC:FP7:ERC,ERC-2012-StG_20111109,CEVAL(2013), and European Project: 305421,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EUROFANCOLEN(2013)

Subjects
MDM4, Fanconi anemia, precision medicine, [SDV]Life Sciences [q-bio], Genetics, leukemia, clonal hematopoiesis, Molecular Medicine, Cell Biology, TP53, mutational signature, genomic instability, BRCA2
Abstract

International audience; Fanconi anemia (FA) patients experience chromosome instability, yielding hematopoietic stem/progenitor cell (HSPC) exhaustion and predisposition to poor-prognosis myeloid leukemia. Based on a longitudinal cohort of 335 patients, we performed clinical, genomic, and functional studies in 62 patients with clonal evolution. We found a unique pattern of somatic structural variants and mutations that shares features of BRCA-related cancers, the FA-hallmark being unbalanced, microhomology-mediated translocations driving copy-number alterations. Half the patients developed chromosome 1q gain, driving clonal hematopoiesis through MDM4 trisomy downmodulating p53 signaling later followed by secondary acute myeloid lukemia genomic alterations. Functionally, MDM4 triplication conferred greater fitness to murine and human primary FA HSPCs, rescued inflammation-mediated bone marrow failure, and drove clonal dominance in FA mouse models, while targeting MDM4 impaired leukemia cells in vitro and in vivo. Our results identify a linear route toward secondary leukemogenesis whereby early MDM4-driven downregulation of basal p53 activation plays a pivotal role, opening monitoring and therapeutic prospects.

Published
2023
Full Text
View/download PDF

2. Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study

Author

Aude Marie-Cardine, Flore Sicre de Fontbrune, Stéphane Blanche, Despina Moushous, Thierry Leblanc, Christine Bellanné-Chantelot, Fanny Rialland, Nathalie Aladjidi, Claire Freycon, Virginie Gandemer, Catherine Paillard, Blandine Beaupain, Marlène Pasquet, French Severe Chronic Neutropenia Registry, Marie-Gabrielle Vigue, Wadih Abou-Chahla, Christophe Piguet, Frédéric Millot, Martin Biosse-Duplan, Pacifique Lévy, Cecile Renard, Jean Donadieu, Gioacchino Andrea Rotulo, Geneviève Plat, Vincent Barlogis, Claire Fieschi, Therapeia Rehabilitation Center, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Registre des neutropénies chroniques [CHU Trousseau], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital des Enfants, CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), CHU Strasbourg, CHU Bordeaux [Bordeaux], Hôpital Bretonneau, Amgen SAS, Chugai SA, Inserm, Association Sportive de Saint-Quentin–Fallavier, Société d’Hémato-Immunologie Pédiatrique, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Adult, medicine.medical_specialty, Neutropenia, Adolescent, severe congenital neutropenia, [SDV]Life Sciences [q-bio], Disease, medicine.disease_cause, 03 medical and health sciences, Cyclic neutropenia, Young Adult, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Registries, Child, 030304 developmental biology, 0303 health sciences, ELANE-related neutropenia, business.industry, Elastase, Hematopoietic Stem Cell Transplantation, Genetic Variation, Infant, Hematology, Bacterial Infections, medicine.disease, opportunistic infections, 3. Good health, Transplantation, Pneumonia, Mycoses, Staphylococcus aureus, 030220 oncology & carcinogenesis, Cellulitis, France, business, Leukocyte Elastase, Follow-Up Studies
Abstract

International audience; Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease’s natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37·4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (3000/mm(3) ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.

Published
2021
Full Text
View/download PDF

3. Scedosporiosis/lomentosporiosis observational study (SOS): Clinical significance of Scedosporium species identification

Author

Boris Melloni, Benoit Roze, Lilia Hasseine, Jacques-Olivier Bay, Laurence Delhaes, Dominique Toubas, Gaelle Guillerm, Xavier Iriart, Thomas Similowski, Valérie Letscher-Bru, Liana Carausu, Adela Angoulvant, Eric Caumes, Marie-Elisabeth Bougnoux, Yves Leprince, Taieb Chouaki, Cécile Molucon-Chabrot, Eric Dannaoui, Hervé Dutronc, Youssef El-Samad, Florent Morio, Morgane Mourguet, Alexandre Alanio, Berengere Gruson, Pierre Cahen, Stéphane Ranque, Anne Boullié, Julie Bonhomme, Violaine Noel, Françoise Dromer, Elisabeth Chachaty, Felipe Suarez, Beate Heym, François Bissuel, Cécile Jensen, Jean-Pierre Gangneux, Emmanuelle Mouchon, Philippe Zann, Patricia Mariani, Bernard Bouteille, Véronique Leflon-Guibout, Dea Garcia-Hermoso, Anne Scemla, Stéphane Blanche, Agnes Lefort, Dorothée Raoux-Barbot, Didier Bronnimann, Olivier Lortholary, Matthieu Revest, Fanny Lanternier, Philippe Poirier, Luc Quaesaet, Marie Machouart, Françoise Botterel-Chartier, Viviane Queyrel-Moranne, Thomas Perpoint, Anne De Tinteniac, Pascale Penn, Ana Presedo, Marie Balsat, Anne Huynh, Lelia Escaut, Noémie Gadaud, Antoine Huguenin, Martine Gari-Toussaint, Sophie Brun, Jean-Marie Forel, Blandine Rammaert, Nicole Desbois, Alain Delmer, Valérie Moal, Arnaud Fekkar, Damien Hoinard, Elizabeth Rivaud, Delphine Lancement, Laurence Pougnet, Valérie Zeller, Jacques Grill, Florence Pasquier, Fabrice Larosa, Jean-François Papon, Nina Arakelyan-Laboure, Thomas Daix, Catherine Cordonnier, Nicolas Limal, Patrick Lutz, Laurence Maulin, Céline Nourrisson, Stéphane Bretagne, Françoise Uettwiller, Florence Ader, Céline Dieval, Nicolas Traversier, Sophie Bayle, Sorya Belaz, Frédéric Villega, Flore Sicre De Fontbrune, Didier Poisson, Olivier Moquet, Guillaume Martin-Blondel, Kamel Laribi, Delphine Horeau-Langlard, Gilles Nevez, Stéphanie Branger, Audrey Hessel, Philippe Herman, Jérémie Orain, Emilie Catherinot, Frédéric Mechai, Cristina Audoly, Frédéric Gabriel, Jean-François Velly, Caroline Fritz, Muriel Alvarez, Romain Guillemain, Pascal Turlure, Grégoire Leclerc, Frederic Pene, Lionel Mannone, Frédéric Grenouillet, Yoann Prevot, Louis-Jean Couderc, Isabelle Degasne, Giovanna Ingenuo, Joséphine Dorin, Florence Persat, Pierre-Marie Roger, Nathalie Brieu, David Boutoille, Pierre Frange, Nicolas Paleiron, Christophe Joubert, Laurent Hustache-Mathieu, Raoul Herbrecht, Frédéric Janvier, Lenaïg Le Clech, Cécile Gautier, Joelle Guitard, Nicolas Durrleman, Romain Guery, Stéphane De Botton, Sophie Cassaing, Marine Paul, Rachel Brault, Claire Briere-Bellier, Catherine Kauffmann-Lacroix, Nicolas Engrand, Audrey Berric, Hôpital Henri Mondor, Diane Bouvry, André Paugam, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Victor Segalen - Bordeaux 2, Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier du Pays d'Aix, CHU Amiens-Picardie, The National Reference Center for Invasive Mycoses and Antifungals is supported in part by Santé Publique France and Institut Pasteur., Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris], and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]

Subjects
Adult, Male, medicine.medical_specialty, Antifungal Agents, Adolescent, LOMENTOSPORA PROLIFICANS, Lomentospora prolificans, Microbial Sensitivity Tests, Neutropenia, Scedosporium sp, Scedosporium, Young Adult, 03 medical and health sciences, Scedosporium species, Internal medicine, Humans, Medicine, Clinical significance, Child, Mycological Typing Techniques, scedosporiosis, Phylogeny, Fungemia, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Retrospective Studies, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, 030306 microbiology, business.industry, Infant, Newborn, Infant, Scedosporium apiospermum, General Medicine, Middle Aged, medicine.disease, cardiovascular localization, 3. Good health, Infectious Diseases, Child, Preschool, outcome, Female, Observational study, France, business, Invasive Fungal Infections
Abstract

International audience; Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes.

Published
2020
Full Text
View/download PDF

4. Human-Derived α1-Antitrypsin is Still Efficacious in Heavily Pretreated Patients with Steroid-Resistant Gastrointestinal Graft-versus-Host Disease

Author

Aurélien Sutra Del Galy, Aliénor Xhaard, Hélène Moins-Teisserenc, Marie Robin, Livia Giannoni, Marine Peyneau, Marie Hélène Schlageter, Régis Peffault de Latour, Simona Pagliuca, David Michonneau, Gérard Socié, Florence Morin, Deborah Desmier, Flore Sicre de Fontbrune, Nathalie Dhedin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Milétrie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier

Subjects
medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Enteropathy, Normal range, Feces, Retrospective Studies, Transplantation, business.industry, Remission Induction, Hematology, medicine.disease, Steroid resistant, Alpha-1 antitrypsin, Confidence interval, 3. Good health, Treatment, [SDV] Life Sciences [q-bio], Intestinal Diseases, Graft-versus-host disease, α1 antitrypsin, 030220 oncology & carcinogenesis, Allogeneic hematopoietic stem cell transplantation, Steroid-resistant graft-versus-host disease, Steroids, business, 030215 immunology
Abstract

International audience; Almost one-half of patients developing graft-versus-host disease (GVHD) will not respond to standard first-line steroid treatment. Alpha-1 antitrypsin (AAT) is able to induce tolerance in preclinical models of GVHD. AAT alters the cytokine milieu, promotes a tolerogenic shift of dendritic cells, and skews effector T cells toward regulatory T cells. Gastrointestinal steroid-refractory (SR)-GVHD is a protein-losing enteropathy that might represent the optimal setting in which to use AAT. Here we analyze the outcomes of 16 patients treated with human-derived AAT in advanced-stage gut SR-GVHD, with two-thirds of the patients having failed at least 1 treatment for SR-GVHD. The overall response rate (ORR) was 44%, with a complete response (CR) rate of 27%. Gastrointestinal response was observed in 61% of patients. The median time to best response was 21 days (range, 6 to 26 days). At day 56 after AAT treatment, all CRs were maintained, and the ORR was 39%. The 1-year overall survival was 48% (95% confidence interval, 26% to 74%). Ancillary studies showed that AAT serum levels were in the normal range at the beginning of treatment, whereas fecal loss was elevated. AAT levels consistently rose after exogenous administration, but no correlation was found between serum levels and response. REG3α and IL-33 levels were associated with response while, in contrast to previous reports, regulatory T cells decreased during AAT treatment. This retrospective analysis supports a previous report of AAT as a promising agent in the management of gut SR-GVHD and should prompt its evaluation at an earlier stage.

Published
2020
Full Text
View/download PDF

5. HSCT may lower leukemia risk in ELANE neutropenia: a before–after study from the French Severe Congenital Neutropenia Registry

Author

Yves Bertrand, Blandine Beaupain, Despina Moshous, Ouahiba Nachit, Nathalie Aladjdi, Bruno Filhon, Flore Sicre de Fontbrune, Christine Bellanné-Chantelot, Jean-Hugues Dalle, Benedicte Neven, Gioacchino Andrea Rotulo, Fanny Rialland, J. Donadieu, Marie Ouachee, E. Dore, Catherine Paillard, Claire Galambrun, Virginie Gandemer, Regis Peffault de la Tour, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universita degli studi di Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Strasbourg (UNISTRA), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, CHU Bordeaux [Bordeaux], CHU Rouen, Normandie Université (NU), Hopital Saint-Louis [AP-HP] (AP-HP), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Pediatrics, medicine.medical_specialty, Neutropenia, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Congenital Bone Marrow Failure Syndromes, Humans, Medicine, Registries, Congenital Neutropenia, Before after study, Transplantation, Acute leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, 3. Good health, Leukemia, Controlled Before-After Studies, 030220 oncology & carcinogenesis, Cohort, France, business, 030215 immunology
Abstract

International audience; ELANE neutropenia is associated with myelodysplasia and acute leukemia (MDS–AL), and severe infections. Because the MDS–AL risk has also been shown to be associated with exposure to GCSF, since 2005, in France, patients receiving high daily GCSF doses (>15 μg/kg/day) are eligible for HSCT, in addition to classic indications (MDS–AL or GCSF refractoriness). We analyzed the effect of this policy. Among 144 prospectively followed ELANE-neutropenia patients enrolled in the French Severe Congenital Neutropenia Registry, we defined two groups according to period: “before 2005” for those born before 2005 and followed until 31/12/2004 (1588 person-years); and “after 2005” comprised of those born after 2005 or born before 2005 but followed after 2005 until 31/03/2019 (1327 person-years). Sixteen of our cohort patients underwent HSCT (14 long-term survivors) and six developed MDS–ALs. Six leukemic transformations occurred in the before-2005 group and none after 2005 (respective frequencies 3.8 × 10–3 vs. 0; P

Published
2020
Full Text
View/download PDF

6. Should Transplantation Still Be Considered for Ph1-Negative Myeloproliferative Neoplasms in Transformation?

Author

David Michonneau, Gérard Socié, Flore Sicre de Fontbrune, Lionel Ades, Bruno Cassinat, Raphael Itzykson, Mathilde Ruggiu, Emmanuelle Clappier, Jean-Jacques Kiladjian, Marie Robin, Emmanuel Raffoux, Stéphane Giraudier, Régis Peffault de Latour, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976))

Subjects
medicine.medical_specialty, Allogeneic transplantation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Patient age, Neoplasms, Internal medicine, Overall survival, Humans, Transplantation, Homologous, Medicine, Retrospective Studies, Transplantation, Chemotherapy, Myeloproliferative Disorders, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, 3. Good health, Child, Preschool, 030220 oncology & carcinogenesis, Cohort, business, 030215 immunology
Abstract

BCR-ABL-negative myeloproliferative neoplasms (MPNs) in transformation have a dismal prognosis, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the sole curative therapeutic option. We retrospectively analyzed 53 molecularly annotated patients treated at Saint Louis Hospital, Paris, diagnosed with MPN in transformation between 2008 and 2018. The median patient age was 65 years, and the median interval between MPN diagnosis and MPN transformation was 46 months. The median overall survival (OS) of the entire cohort after transformation was 7.1 months. OS was better for patients treated with hypomethylating agents (HMAs) or with chemotherapy compared than for those treated by best supportive care or single-agent targeted therapy (median, 9.1 months versus 1.5 months; P.001). Patients treated with chemotherapy more often achieved complete remission compared with those treated with HMAs (68% versus 29%; P = .02), and were more often candidates for transplantation (59% versus 14%; P = .02), but the median OS was similar in the 2 groups. We then compared the outcomes in transplant recipients and nonrecipients using the Mantel-Byar methodology and found that allo-HSCT did not improve survival. In multivariate analysis, independent factors in prognosis were performance status at transformation (P.01), initial treatment with HMAs or chemotherapy (P = .02), and the ability to achieve complete remission during follow-up (P.01). Our data demonstrate that the indication for allo-HSCT for high-risk MPN should be discussed before transformation, because transplantation rescues few patients after transformation.

Published
2020
Full Text
View/download PDF

7. Letermovir for Secondary Prophylaxis of Cytomegalovirus Infection and Disease after Allogeneic Hematopoietic Cell Transplantation: Results from the French Compassionate Program

Author

Rabah Redjoul, Maud d'Aveni, Golriz Pahlavan-Grumel, Flore Sicre de Fontbrune, Nathalie Bénard, Stephanie Nguyen-Quoc, Catherine Cordonnier, Christine Robin, Sophie Alain, Ana Berceanu, Patrice Ceballos, Anne Thiebaut, CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire [Grenoble] (CHU), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), CHU Saint-Eloi, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MSD France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, medicine.medical_specialty, Congenital cytomegalovirus infection, Disease, Acetates, 030230 surgery, Antiviral Agents, 03 medical and health sciences, Letermovir, 0302 clinical medicine, Immune system, Internal medicine, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Adverse effect, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Cytopenia, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, 3. Good health, Cytomegalovirus Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Quinazolines, business, medicine.drug
Abstract

Letermovir potently inhibits the cytomegalovirus (CMV)-terminase complex. Letermovir primary prophylaxis given for the first 3 months after allogeneic hematopoietic cell transplantation (HCT) has been shown to reduce clinically significant CMV infection and is well tolerated. Until now, only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis (SP) of CMV infection or diseases after HCT. Here we report the outcome of 80 consecutive CMV-seropositive adult patients included in the French compassionate program and who received letermovir as a SP after at least 1 CMV episode (infection or disease) since HCT. Letermovir was initiated at a median of 170 (49 to 1829) days after transplant and given orally for a median of 118 (26 to 396) days at the usual daily dose of 480 mg once daily and adjusted to 240 mg once daily when coadministered with cyclosporine. The donors were seronegative in 53% of the cases. Fifty patients had a current or previous graft-versus-host disease (GVHD) and 14 had experienced CMV disease since transplant. Four (5.5%) patients developed CMV breakthrough infections (n = 1) or diseases (n = 3) after the initiation of letermovir. In 3 of these 4 patients, further investigation of virologic resistance showed a CMV UL56 mutation C325Y or W, conferring the high-level letermovir resistance. One or more adverse reactions were declared by the local investigator in 15 (19%) patients. Only 2 patients stopped letermovir SP because of an adverse reaction (pruritus, 1; cytopenia, 1). In our experience, letermovir given as a SP may prevent a new CMV reactivation in a high-risk patient population and can be administered for several weeks, providing a bridge between the pre-emptive or therapeutic treatment of a CMV episode and CMV-specific immune reconstitution, giving time for tapering immunosuppressants. Prospective studies are required to confirm these results.

Published
2020
Full Text
View/download PDF

8. Romiplostim in patients undergoing hematopoietic stem cell transplantation: results of a phase 1/2 multicenter trial

Author

Flore Sicre de Fontbrune, Marie-Thérèse Rubio, Stéphanie Nguyen, Sylvie Chevret, Régis Peffault de Latour, Mohamad Mohty, Laetitia Souchet, Nathalie Dhedin, David Michonneau, Tereza Coman, Gérard Socié, Anna Lisa Ruggeri, Felipe Suarez, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], CHU Necker - Enfants Malades [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Oncology, medicine.medical_specialty, medicine.medical_treatment, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Multicenter trial, Internal medicine, medicine, Aplastic anemia, Thrombopoietin, ComputingMilieux_MISCELLANEOUS, Romiplostim, business.industry, Cell Biology, Hematology, medicine.disease, 3. Good health, Clinical trial, Transplantation, 030220 oncology & carcinogenesis, Stem cell, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract

Persisting severe thrombocytopenia more than 6 weeks after allogeneic stem cell transplantation is a common problem associated with adverse prognosis. Peffault de Latour et al report the results of the first trial of the thrombopoietin mimetic, romiplostim, in this setting, demonstrating recovery of platelet counts in 18 of 24 patients.

Published
2020
Full Text
View/download PDF

9. Epstein-Barr Virus-Associated Post-Transplantation Lymphoproliferative Disease in Patients Who Received Anti-CD20 after Hematopoietic Stem Cell Transplantation

Author

Flore Sicre de Fontbrune, Aliénor Xhaard, Côme Bommier, Pedro Henrique Prata, Simona Pagliuca, David Michonneau, Jérôme Le Goff, Nathalie Dhedin, Véronique Meignin, Gérard Socié, Maud Salmona, Marie Robin, Régis Peffault de Latour, Sophie Caillat-Zucman, Linda Feghoul, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier

Subjects
Adult, Male, Epstein-Barr Virus Infections, Herpesvirus 4, Human, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Epstein-Barr virus infection, Hematopoietic stem cell transplantation, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Child, Epstein–Barr virus infection, Aged, Retrospective Studies, Transplantation, Anti-CD20 therapy, business.industry, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, Epstein–Barr virus, Lymphoproliferative Disorders, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], surgical procedures, operative, 030220 oncology & carcinogenesis, Post-transplantation lymphoproliferative disease, Cohort, Female, Rituximab, business, Complication, Follow-Up Studies, HLA-DRB1 Chains, 030215 immunology, medicine.drug
Abstract

International audience; Post-transplantation lymphoproliferative disease (PTLD) is a serious complication associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although anti-CD-20 therapy is now used as a preemptive strategy for EBV reactivation, PTLD still occurs in some patients. Here we analyzed outcomes and risk factors associated with PTLD transformation in 208 HSCT recipients who were diagnosed with EBV-DNAemia and received at least 1 course of rituximab. The median patient age was 42.52 years (range, 8.35 to 74.77 years), and the median duration of follow-up was 47.33 months (range, 3.18 to 126.20 months). The 2-year overall survival of the entire cohort was 62.8 (95% confidence interval [CI], 56.4 to 69.9), and the 2-year cumulative incidence function of PTLD was 6.3% (95% CI, 3.5% to 10.1%), for a median follow-up of patients diagnosed with PTLD of 37.85 months. Multivariable analysis identified 4 risk factors associated with PTLD: HSCT from an unrelated donor, recipient HLA-DRB1*11:01, fever at diagnosis of EBV infection, and donor-recipient sex-mismatched HSCT. The presence of more than 2 of these risk factors was associated with an increased risk of developing PTLD. This retrospective study identifies risk factors associated with PTLD in EBV-infected patients after HSCT and defines patient subgroups that may benefit from intensified preemptive strategies.

Published
2019
Full Text
View/download PDF

10. Nationwide survey on the use of horse antithymocyte globulins (ATGAM) in patients with acquired aplastic anemia: A report on behalf of the French Reference Center for Aplastic Anemia

Author

Suzanne Tavitian, Mohamad Mohty, Marlène Pasquet, Reza Tabrizi, Régis Peffault de Latour, Claire Galambrun, Jean-Yves Cahn, Thierry Leblanc, Fiorenza Barraco, Thorsten Braun, Thierry Lamy, Charlotte Jubert, Jacques-Olivier Bay, Flore Sicre de Fontbrune, Stéphanie Nguyen, Eric Deconinck, Ambroise Marçais, Gérard Socié, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Anemia, Hemorrhage, Infections, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Randomized controlled trial, law, Surveys and Questionnaires, Internal medicine, medicine, Animals, Humans, Horses, Young adult, Aplastic anemia, Child, Adverse effect, ComputingMilieux_MISCELLANEOUS, Antilymphocyte Serum, business.industry, Anemia, Aplastic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, 3. Good health, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Cyclosporine, Drug Therapy, Combination, Female, France, business, 030215 immunology
Abstract

Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first-line treatment of severe AA. The French Health Agency (ANSM) permitted a patient-named authorization for temporary use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received antithymocyte globulins (ATGAM) plus CSA as first line treatment (n = 379; 81.5%), or for refractory (n = 26) or relapsed disease (n = 33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%), and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty-five patients died during the study mainly because of infections (53%). Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5 × 109 /L, male gender and longer delay between diagnosis and hATG (>6 months period). This study does illustrate the results of ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT.

Published
2018
Full Text
View/download PDF

11. 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
Full Text
View/download PDF

12. Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia

Author

Paul Coppo, Régis Peffault de Latour, Brigitte Dupriez, Gérard Socié, Ana Berceanu, Lionel Adès, Louis Terriou, Natacha Maillard, Julie Abraham, Flore Sicre de Fontbrune, Thierry Leblanc, Driss Chaoui, Marie Balsat, Bernard Drenou, Etienne Lengliné, Emmanuel Raffoux, Gaelle Guillerm, Selim Corm, Pierre Peterlin, Olivier Tournilhac, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département d'hématologie, Centre Hospitalier de Lens, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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 [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'Hématologie, Argenteuil, Centre Hospitalier Victor Dupouy, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, 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), 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)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], 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 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, CHU Saint-Antoine [APHP], Lille Inflammation Research International Center (LIRIC), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Male, medicine.medical_specialty, Pediatrics, Anemia, Eltrombopag, Salvage therapy, Benzoates, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Refractory, Interquartile range, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Aplastic anemia, ComputingMilieux_MISCELLANEOUS, Aged, Antilymphocyte Serum, Retrospective Studies, Salvage Therapy, business.industry, Anemia, Aplastic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Bone Marrow Failure, 3. Good health, Surgery, Transplantation, Platelet transfusion, Hydrazines, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Pyrazoles, Female, France, business, 030215 immunology
Abstract

Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naive patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×109/L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naive and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.

Published
2018
Full Text
View/download PDF

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

Author

Lucie Hernandez, Samuel Quentin, Elodie Lainey, Thierry Leblanc, Nicolas Boissel, Etienne Lengliné, Jean-Hugues Dalle, Julien Masliah-Planchon, Gérard Michel, Lionel Adès, Régis Peffault de Latour, Louis De Jaegere, Yves Bertrand, André Baruchel, Guy Leverger, Marie Sebert, Naddia Vasquez, Emmanuelle Clappier, Marc Muller, Olivier Bluteau, Stéphane Blanche, Isabelle Pellier, Gérard Socié, Wendy Cuccuini, Carine Domenech, Mathilde Hunault, Nicolas Blin, Raphael Itzykson, Sébastien Maury, Pierre Fenaux, Bénédicte Bruno, Mélanie Da Costa, Anna Raimbault, Jean Soulier, Claudine Schmitt, Arnaud Petit, Flore Sicre de Fontbrune, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Recherche clinique appliquée à l'hématologie (URP_3518), Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Service d'hématologie pédiatrique [Robert-Debré - APHP], Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Laboratoire d’Hématologie [CHU Henri-Mondor - APHP], CHU Henri Mondor, Service d'Hématologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique [CHRU Nancy], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Henri Mondor [Créteil], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, MECOM, DNA Mutational Analysis, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, Cohort Studies, 03 medical and health sciences, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Fanconi anemia, Internal medicine, hemic and lymphatic diseases, Exome Sequencing, medicine, Humans, Child, Bone Marrow Diseases, Germ-Line Mutation, Exome sequencing, Chromosome 7 (human), business.industry, Infant, Newborn, Bone marrow failure, High-Throughput Nucleotide Sequencing, Infant, Cell Biology, Hematology, medicine.disease, Pancytopenia, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Child, Preschool, Myelodysplastic Syndromes, Female, Bone marrow, business
Abstract

International audience; Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders (GATA2, RUNX1), telomeropathies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling.

Published
2018
Full Text
View/download PDF

14. Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study

Author

Catherine Paillard, Mohamad Mohty, Claire Galambrun, Charlotte Jubert, Gérard Socié, Fanny Rialland, Eliane Gluckman, Jérôme Larghero, S. Furst, Annalisa Ruggeri, Marie-Thérèse Rubio, Virginie Gandemer, Jacques-Olivier Bay, Jean-Hugues Dalle, Sylvie Chevret, Flore Sicre de Fontbrune, Régis Peffault de Latour, Bénédicte Bruno, Anne Sirvent, Edouard Forcade, Jérôme Cornillon, Pierre S. Rorlich, Alexandra Salmon, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Anemia, Immunology, Graft vs Host Disease, Cord Blood Stem Cell Transplantation, Biochemistry, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Aplastic anemia, Child, Survival rate, ComputingMilieux_MISCELLANEOUS, Antilymphocyte Serum, Alanine, business.industry, Umbilical Cord Blood Transplantation, Anemia, Aplastic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Total body irradiation, Allografts, medicine.disease, 3. Good health, Survival Rate, Transplantation, 030220 oncology & carcinogenesis, Acute Disease, Female, Unrelated Donors, business, Whole-Body Irradiation, 030215 immunology
Abstract

Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results