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1. Progressive multifocal leukoencephalopathy after durvalumab treatment for acute myeloid leukemia: A consequence of an immune reconstitution inflammatory syndrome?

Author

Emeline Vinatier, Caroline Poli, Aurélien Giltat, Christopher Nunes‐Gomes, Corentin Orvain, Mathilde Hunault‐Berger, Pascale Jeannin, and Sylvain Thépot

Subjects
acute leukemia, immunopathology, immunotherapy, infection, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the reactivation of the John Cunningham virus (JCV). PML occurs almost exclusively during profound immune suppression but it can also be observed in immunocompromised subjects as part of an inflammatory immune reconstitution syndrome (IRIS) in patients receiving antiviral therapy. We report a case of PML in a 61‐year‐old patient with acute myeloid leukemia who had developed after discontinuation of durvalumab (anti‐PD‐L1) therapy initiated after multiple treatments. Results suggest that PML may result from two nonexclusive mechanisms: (i) an inhibition of the protective response of JCV‐specific T cells as a consequence of the blockade of the PD1‐PDL1 pathway, associated with a lack of compensatory expression of other inhibitory receptors by T cells and (ii) a neuroinflammatory response (PML‐IRIS) that may have contributed to virus reactivation.

Published
2022
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2. Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study

Author

Corentin Orvain, Sylvain Chantepie, Xavier Thomas, Martine Escofrre-Barbe, Francoise Huguet, Yohan Desbrosses, Gaelle Guillerm, Madalina Uzunov, Thibaut Leguay, Sarah Barbieux, Norbert Vey, Patrice Chevallier, Jean-Valere Malfuson, Stephane Lepretre, Michael Baumann, Murat Aykut, Abdelaziz Chaib, Magalie Joris, Hacene Zerazhi, Georg Stussi, Jacques Chapiro, Celine Berthon, Caroline Bonmati, Eric Jourdan, Diana Carp, Amb roise Marcais, Maria-Pilar Gallego-Hernanz, Iona Vaida, Karin Bilger, Alban Villate, Florence Pasquier, Yves Chalandon, Sebastien Maury, Veronique Lheritier, Norbert Ifrah, Herve Dombret, Nicolas Boissel, and Mathilde Hunault-Berger.

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been formerly re-evaluated. We report here the outcome of patients with initial CNS involvement included in the pediatric-inspired prospective randomized GRAALL-2005 study. Between 2006 and 2014, 784 adult patients (aged 18-59 years) with newly diagnosed Philadelphia-negative ALL were included, of whom 55 (7%) had CNS involvement. In CNSpositive patients, overall survival was shorter (median 1.9 years vs. not reached, HR=1.8 [1.3-2.6], P

Published
2023
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3. Improved survival with enasidenib versus standard of care in relapsed/refractory acute myeloid leukemia associated with IDH2 mutations using historical data and propensity score matching analysis

Author

Stéphane deBotton, Joseph M. Brandwein, Andrew H. Wei, Arnaud Pigneux, Bruno Quesnel, Xavier Thomas, Ollivier Legrand, Christian Recher, Sylvain Chantepie, Mathilde Hunault‐Berger, Nicolas Boissel, Salem A. Nehme, Mark G. Frattini, Alessandra Tosolini, Roland Marion‐Gallois, Jixian J. Wang, Chris Cameron, Muhaimen Siddiqui, Brian Hutton, Gary Milkovich, and Eytan M. Stein

Subjects
acute myeloid leukemia, enasidenib, IDH2 mutations, overall survival, standard of care, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT). Methods Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221‐C‐001 trial and SoC outcomes obtained from a real‐world chart review of patients in France. Results Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61–1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47–0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72–13.24) and 4.76 months for SoC (95% CI, 3.81–8.21). Results remained robust across all sensitivity analyses conducted. Conclusions PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes.

Published
2021
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4. Daunorubicin and Its Active Metabolite Pharmacokinetic Profiles in Acute Myeloid Leukaemia Patients: A Pharmacokinetic Ancillary Study of the BIG-1 Trial

Author

Guillaume Drevin, Marie Briet, Caroline Bazzoli, Emmanuel Gyan, Aline Schmidt, Hervé Dombret, Corentin Orvain, Aurelien Giltat, Christian Recher, Norbert Ifrah, Philippe Guardiola, Mathilde Hunault-Berger, and Chadi Abbara

Subjects
daunorubicin, pharmacokinetics, acute myeloid leukaemia, modelling, Pharmacy and materia medica, RS1-441
Abstract

Daunorubicin pharmacokinetics (PK) are characterised by an important inter-individual variability, which raises questions about the optimal dose regimen in patients with acute myeloid leukaemia. The aim of the study is to assess the joint daunorubicin/daunorubicinol PK profile and to define an optimal population PK study design. Fourteen patients were enrolled in the PK ancillary study of the BIG-1 trial and 6–8 samples were taken up to 24 h after administration of the first dose of daunorubicin (90 mg/m2/day). Daunorubicin and daunorubicinol quantifications were assessed using a validated liquid chromatography technique coupled with a fluorescence detector method. Data were analysed using a non-compartmental approach and non-linear mixed effects modelling. Optimal sampling strategy was proposed using the R function PFIM. The median daunorubicin and daunorubicinol AUC0-tlast were 577 ng/mL·hr (Range: 375–1167) and 2200 ng/mL·hr (range: 933–4683), respectively. The median metabolic ratio was 0.32 (range: 0.1–0.44). Daunorubicin PK was best described by a three-compartment parent, two-compartment metabolite model, with a double first-order transformation of daunorubicin to metabolite. Body surface area and plasma creatinine had a significant impact on the daunorubicin and daunorubicinol PK. A practical optimal population design has been derived from this model with five sampling times per subject (0.5, 0.75, 2, 9, 24 h) and this can be used for a future population PK study.

Published
2022
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5. Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Xavier Poiré, Myriam Labopin, Emmanuelle Polge, Jakob Passweg, Charles Craddock, Didier Blaise, Jan J. Cornelissen, Liisa Volin, Nigel H. Russell, Gérard Socié, Mauricette Michallet, Nathalie Fegueux, Patrice Chevallier, Arne Brecht, Mathilde Hunault-Berger, Mohamad Mohty, Jordi Esteve, and Arnon Nagler

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (P

Published
2018
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6. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

Author

Julien Lazarovici, Peggy Dartigues, Pauline Brice, Lucie Obéric, Isabelle Gaillard, Mathilde Hunault-Berger, Florence Broussais-Guillaumot, Emmanuel Gyan, Serge Bologna, Emmanuelle Nicolas-Virelizier, Mohamed Touati, Olivier Casasnovas, Richard Delarue, Frédérique Orsini-Piocelle, Aspasia Stamatoullas, Jean Gabarre, Luc-Matthieu Fornecker, Thomas Gastinne, Fréderic Peyrade, Virginie Roland, Emmanuel Bachy, Marc André, Nicolas Mounier, and Christophe Fermé

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.

Published
2015
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7. A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

Author

Mathilde Hunault-Berger, Thibaut Leguay, Xavier Thomas, Ollivier Legrand, Françoise Huguet, Caroline Bonmati, Martine Escoffre-Barbe, Laurence Legros, Pascal Turlure, Patrice Chevallier, Fabrice Larosa, Frederic Garban, Oumedaly Reman, Philippe Rousselot, Nathalie Dhédin, André Delannoy, Marina Lafage-Pochitaloff, Marie Christine Béné, Norbert Ifrah, and Hervé Dombret

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia.Design and Methods Sixty patients received either continuous-infusion doxorubicin (12 mg/m2/day) and continuous-infusion vincristine (0.4 mg/day) on days 1–4 or pegylated liposomal doxorubicin (40 mg/m2) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors.Results Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm.Conclusions With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities.

Published
2011
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8. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study

Author

Mathilde Hunault-Berger, Patrice Chevallier, Martine Delain, Claude-Eric Bulabois, Serge Bologna, Marc Bernard, Ingrid Lafon, Jérome Cornillon, Abdallah Maakaroun, Alexandra Tizon, Bruno Padrazzi, Norbert Ifrah, and Yves Gruel

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background The effects of L-asparaginase on hemostasis during induction chemotherapy are less defined in adults than in children. We, therefore, studied the effects of L-asparaginase in adult patients.Design and Methods This was a retrospective analysis of 214 patients treated with L-asparaginase (7500 IU/m2 x 6) for acute lymphoblastic leukemia or lymphoblastic lymphoma. Between day 1 of the induction course and discharge, clinical events, and biological and therapeutic modifications were reviewed.Results Antithrombin and fibrinogen levels were lower than 60% and 1 g/L in 71% and 73% of patients, respectively. Twenty thromboses occurred in 9.3% of the patients; these patients had a median antithrombin level of 53% (range, 21–111) at the time of the event. Forty-two episodes of bleeding occurred in 31 patients with a median fibrinogen level of 1.3 g/L. Infusions of L-asparaginase were reduced or delayed in 64% of patients due to low fibrinogen and/or antithrombin levels. Fresh-frozen plasma, antithrombin and fibrinogen were infused in 31%, 41% and 52% of patients, respectively. The mean antithrombin and fibrinogen levels increased from 61% to 88% and from 1 to 1.4 g/L after infusion of antithrombin or fibrinogen respectively, while both levels remained unchanged after the infusion of fresh-frozen plasma. In patients who received antithrombin concentrates L-asparaginase injections were less frequently omitted or delayed (53% vs. 72%, p=0.005), the rate of thrombosis was lower (4.8% vs. 12.2%, p=0.04) and the disease-free survival was also reduced (p=0.05).Conclusions This retrospective study suggests that antithrombin concentrates may have a beneficial effect on the outcome of adults treated for acute lymphoblastic leukemia with L-asparaginase; prospective studies are essential to confirm this hypothesis.

Published
2008
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9. JAK inhibition for CD3− CD4+ lymphocytic-variant hypereosinophilic syndrome

Author

Stanislas Faguer, Matthieu Groh, François Vergez, Mathilde Hunault-Berger, Nicolas Duployez, Yves Renaudineau, Carle Paul, Guillaume Lefevre, Jean-Emmanuel Kahn, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), 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 Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Foch [Suresnes], Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire d'Hématologie [CHRU Lille] (Centre de Biologie et de Pathologie), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Institut Fédératif de Biologie (IFB), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Institute of Chemistry for Life and Health Sciences (iCLeHS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Ambroise Paré [AP-HP]

Subjects
T-cell clone. Copyright © 2023. Published by Elsevier Inc, Ruxolitinib, [SDV]Life Sciences [q-bio], Immunology, Immunology and Allergy, Lymphocytic variant, Hypereosinophilic syndrome, JAK inhibition
Abstract

International audience; Alternatives are urgently needed in patients with CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES) requiring high-level steroids or who are unresponsive and/or intolerant to conventional alternative therapies. We report five L-HES patients (44-66 years) with cutaneous involvement (n = 5) and persistent eosinophilia (n = 3) despite conventional therapies, who successfully received JAK inhibitors (tofacitinib n = 1, ruxolitinib n = 4). JAKi led to complete clinical remission in the first 3 months in all (with prednisone withdrawal in four). Absolute eosinophil counts normalized in cases receiving ruxolitinib, while reduction was partial under tofacitinib. After switch from tofacitinib to ruxolitinib, complete clinical response persisted despite prednisone withdrawal. The clone size remained stable in all patients. After 3-13 months of follow-up, no adverse event was reported. Randomized controlled trials are now mandatory to optimize the use of JAKi in L-HES.

Published
2023

10. In Adults with Ph-Negative Acute Lymphoblastic Leukemia (ALL), Age-Adapted Chemotherapy Intensity and MRD-Driven Transplant Indication Significantly Reduces Treatment-Related Mortality (TRM) and Improves Overall Survival - Results from the Graall-2014 Trial

Author

Boissel, Nicolas, Huguet, Francoise, Leguay, Thibaut, Mathilde, Hunault-Berger, Graux, Carlos, Chalandon, Yves, Delabesse, Eric, Hicheri, Yosr, Chevallier, Patrice, Balsat, Marie, Pastoret, Cedric, Escoffre-Barbe, Martine, Pasquier, Florence, Marolleau, Jean-Pierre, Thiebaut-Bertrand, Anne, Huynh, Anne, Dhedin, Nathalie, Lemasle, Emilie, Bonmati, Caroline, Maury, Sébastien, Guillerm, Gaëlle, Berceanu, Anna, Schanz, Urs, Cluzeau, Thomas, Turlure, Pascal, Rousselot, Philippe, De Prijck, Bernard J.M., Grardel, Nathalie, Bene, Marie C, Lafage, Marine, Ifrah, Norbert, Lheritier, Veronique, Asnafi, Vahid, Clappier, Emmanuelle, and Dombret, Herve

Published
2022
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11. Dexaml-02 : A Phase II Study of Dexamethasone Added to Induction and Postremission Therapy in Older Patients with Newly Diagnosed AML. a French Innovative Leukemia Organization (FILO) Study

Author

Recher, Christian, Bertoli, Sarah, Peterlin, Pierre, Guieze, Romain, Desbrosses, Yohan, Hicheri, Yosr, Benbrahim, Omar, Carre, Martin, Mathilde, Hunault-Berger, Banos, Anne, Bernard, Marc, Gyan, Emmanuel, Saad, Alain, Chebrek, Safia, Roth Guepin, Gabrielle, Dorvaux, Veronique, Sanhes, Laurence, Gallego Hernanz, Maria Pilar, Exbrayat, Carole, Vincent, Laure, Himberlin, Chantal, Largeaud, Laetitia, Delabesse, Eric, Vergez, Francois, Vey, Norbert, Mineur, Ariane C, Simand, Célestine, Luquet, Isabelle, and Pigneux, Arnaud

Published
2022
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12. Allogeneic Hematopoietic Cell Transplantation in Patients with Therapy-Related Myeloid Neoplasm Following Treatment for Lymphoma: A Study of the Chronic Malignancies Working Party of the EBMT

Author

Nabergoj, Mitja, Eikema, Dirk-Jan, Zinger, Nienke, Platzbecker, Uwe, Sockel, Katja, Finke, Jürgen, Kröger, Nicolaus, Forcade, Edouard, Nagler, Arnon, Ganser, Arnold, Tischer, Johanna, Broers, Annoek E.C., Kuball, Jurgen, Wilson, Keith, Mathilde, Hunault-Berger, Collin, Matthew P., Russo, Domenico, Pérez López, Estefanía, Helbig, Grzegorz, Mussetti, Alberto, Raj, Kavita, Scheid, Christof, McLornan, Donal P., Robin, Marie, and Yakoub-Agha, Ibrahim

Published
2022
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13. Correction to : Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party

Author

Johannes Schetelig, Patrice Chevallier, Michel van Gelder, Jennifer Hoek, Olivier Hermine, Ronjon Chakraverty, Paul Browne, Noel Milpied, Michele Malagola, Gerard Socié, Julio Delgado, Eric Deconinck, Ghandi Damaj, Sebastian Maury, Dietrich Beelen, Stéphanie Nguyen Quoc, Paneesha Shankara, Arne Brecht, Jiri Mayer, Mathilde Hunault-Berger, Jörg Bittenbring, Catherine Thieblemont, Stéphane Lepretre, Henning Baldauf, Liesbeth C. de Wreede, Olivier Tournilhac, Ibrahim Yakoub-Agha, Nicolaus Kröger, Peter Dreger, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)

Subjects
03 medical and health sciences, Transplantation, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medizin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract

The Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party, written by Johannes Schetelig, Patrice Chevallier, Michel van Gelder, Jennifer Hoek, Olivier Hermine, Ronjon Chakraverty, Paul Browne, Noel Milpied, Michele Malagola, Gerard Socié, Julio Delgado, Eric Deconinck, Ghandi Damaj, Sebastian Maury, Dietrich Beelen, Stéphanie Nguyen Quoc, Paneesha Shankara, Arne Brecht, Jiri Mayer, Mathilde Hunault-Berger, Jörg Bittenbring, Catherine Thieblemont, Stéphane Lepretre, Henning Baldauf, Liesbeth C. de Wreede, Olivier Tournilhac, Ibrahim Yakoub-Agha, Nicolaus Kröger, Peter Dreger was originally published Online First without Open Access. After publication in volume 56, issue 3, page 605–613 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0. Open access funding enabled and organized by Projekt DEAL. Korrektur zu 10.1038/s41409-020-01069-w

Published
2022

14. Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Author

Jonathan Farhi, Jérôme Paillassa, Aurelien Giltat, Emmanuel Gyan, Mathilde Hunault-Berger, Tony Marchand, Mélanie Mercier, Marie-Christine Rousselet, Roch Houot, Aline Clavert, Christopher Nunes Gomes, Laurianne Drieu La Rochelle, Marie-Pierre Moles-Moreau, and Corentin Orvain

Subjects
Cancer Research, medicine.medical_specialty, Anthracycline, medicine.medical_treatment, lymphoma, Gastroenterology, bone, Article, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, high-dose methotrexate, RC254-282, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, skeletal, Lymphoma, Radiation therapy, Regimen, Oncology, 030220 oncology & carcinogenesis, Methotrexate, Rituximab, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p &lt, 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p &lt, 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p &lt, 0.001 and 83 vs. 58%, p &lt, 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

Published
2021
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15. CPX-351 in Patients with Newly Diagnosed Post Myeloproliferative Neoplasms Acute Myeloid Leukemia

Author

Garciaz, Sylvain, Belhabri, Amine, Guieze, Romain, Goursaud, Laure, Peterlin, Pierre, Ledoux, Marie-Pierre, Mathilde, Hunault-Berger, Chebrek, Safia, Robin, Jean-Baptiste, Pigneux, Arnaud, Bonnet, Sarah, Bonmati, Caroline, Bertoli, Sarah, Braun, Thorsten, Chantepie, Sylvain, Meunier, Mathieu, Heiblig, Mael, Cluzeau, Thomas, Jourdan, Eric, Villate, Alban, Recher, Christian, Vey, Norbert, and Rey, Jerome

Published
2023
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17. Current Results of Intensive Therapy in Younger Adults with Acute Myeloid Leukemia (AML): The Large Randomized French Backbone Intergroup (BIG)-1 Study on Behalf of the Filo, ALFA, and SFGM-TC Study Groups

Author

Mathilde, Hunault-Berger, Pautas, Cécile, Bertoli, Sarah, Dumas, Pierre-Yves, Raffoux, Emmanuel, Marchand, Tony, Hospital, Marie Anne, Heiblig, Mael, Chantepie, Sylvain, Carré, Martin, Peterlin, Pierre, Lemasle, Emilie, Simand, Célestine, Gallego Hernanz, Maria Pilar, Huynh, Anne, Forcade, Edouard, Devillier, Raynier, Nguyen Quoc, Stéphanie, Duployez, Nicolas, Luquet, Isabelle, Penther, Dominique, Celli-Lebras, Karine, Mineur, Ariane, Gardin, Claude, Socié, Gerard, Cahn, Jean-Yves, Ifrah, Norbert, Vey, Norbert, Peffault De Latour, Regis, Delabesse, Eric, Preudhomme, Claude, Hamel, Jean-François, Pigneux, Arnaud, Recher, Christian, and Dombret, Hervé

Published
2023
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18. Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report

Author

Cabannes-Hamy, Aurelie, Courtois, Lucien, Balsat, Marie, Simonin, Mathieu, Huguet, Françoise, Escoffre-Barbe, Martine, Pasquier, Florence, Bonmati, Caroline, Turlure, Pascal, Cluzeau, Thomas, Lebon, Delphine, Gehlkopf, Eve, Brissot, Eolia, Decroocq, Justine, Chevallier, Patrice, Chantepie, Sylvain, Cacheux, Victoria, Maury, Sebastien, Chebrek, Safia, Leguay, Thibaut, Fort, Melody, Mauz, Natacha, Lamarque, Mathlide, Mathilde, Hunault-Berger, Wickenhauser, Stefan, Frayfer, Jamilé, Banos, Anne, Tavernier, Emmanuelle, Caillot, Denis, Ronchetti, Anne Marie, Berthon, Celine, Lengline, Etienne, Lhéritier, Véronique, Dombret, Hervé, Marçais, Ambroise, Pinton, Antoine, Andrieu, Guillaume P, Boissel, Nicolas, Lhermitte, Ludovic, Asnafi, Vahid, and Rousselot, Philippe

Published
2023
Full Text
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19. Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation

Author

Cedric Pastoret, Yves Delneste, Sylvain Thepot, Marie-Christine Rousselet, Damien Luque Paz, Jean-Marie Chrétien, Maxime Renard, Jean-Christophe Ianotto, Odile Blanchet, Mathilde Hunault-Berger, Jean-Claude Chomel, Anne Murati, Norbert Ifrah, Maria-Pilar Gallego-Hernanz, Isabelle Quintin-Roué, Laurane Cottin, Aurélie Chauveau, Jérémie Riou, Frédéric Courtier, Françoise Boyer, Corentin Orvain, Valérie Ugo, Emilie Cayssials, Rébecca Jouanneau-Courville, Eric Lippert, 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), Laboratoire d'hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service des maladies du sang [CHU Angers], Laboratoire d'hématologie (Labo Hémato - BREST), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Service de Cancérologie Biologique [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers], Laboratoire d'Hematologie [CHU Pontchaillou, Rennes] (Pôle de Biologie), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Laboratoire d'Hématologie et Laboratoire d'Oncologie Moléculaire, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département de Pathologie Cellulaire et Tissulaire, Cellule de Gestion des Données et Evaluation (DRCI), Centre de Ressources Biologiques [CHU Angers], 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), CHU Pontchaillou [Rennes], and Bernardo, Elizabeth

Subjects
Neuroblastoma RAS viral oncogene homolog, IDH1, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, Myeloproliferative Disorders, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Allele, Polycythemia Vera, Gene, 030304 developmental biology, 0303 health sciences, Mutation, Myeloid Neoplasia, Essential thrombocythemia, Genomics, Hematology, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Cancer research, Erratum, Thrombocythemia, Essential
Abstract

Among myeloproliferative neoplasms, polycythemia vera (PV) and essential thrombocythemia (ET) are the 2 entities associated with the most chronic disease course. Leukemic evolution occurs rarely but has a grim prognosis. The interval between diagnosis and leukemic evolution is highly variable, from a few years to >20 years. We performed a molecular evaluation of 49 leukemic transformations of PV and ET by targeted next-generation sequencing. Using a hierarchical classification, we identified 3 molecular groups associated with a distinct time to leukemic transformation. Short-term transformations were mostly characterized by a complex molecular landscape and mutations in IDH1/2, RUNX1, and U2AF1 genes, whereas long-term transformations were associated with mutations in TP53, NRAS, and BCORL1 genes. Studying paired samples from chronic phase and transformation, we detected some mutations already present during the chronic phase, either with a significant allele burden (short-term transformation) or with a very low allele burden (especially TP53 mutations). However, other mutations were not detected even 1 year before leukemic transformation. Our results suggest that the leukemic transformation of PV and ET may be driven by distinct time-dependent molecular mechanisms.

Published
2020

20. Hémorragie intracérébrale fatale chez un patient atteint d'une leucémie chronique à polynucléaires neutrophiles : à propos d'un cas et revue de la littérature

Author

Mathilde Hunault Berger, A.-F. Sapin, Thomas Sinegre, A. Lebreton, L. Talon, B. de Renzis, Laurence Sanhes, M. Fiore, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Ressources et Compétences des Maladies Hémorragiques Constitutionnelles [CHU Clermont-Ferrand] (CRC-MHC), CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand

Subjects
0301 basic medicine, Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Gastroenterology, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal Medicine, medicine, business
Abstract

Resume Introduction La leucemie chronique a neutrophiles (LCN) est un syndrome myeloproliferatif rare caracterise par une production importante de polynucleaires neutrophiles matures. L'une des complications les plus severes est la survenue d'evenements hemorragiques, pouvant parfois conduire au deces des patients. Observation Nous rapportons une observation de LCN affectant un homme de 75 ans. L'observation clinique detaillait de multiples complications hemorragiques. Les explorations biologiques objectivaient des anomalies de l'agregation plaquettaire et une elevation de l'elastase leucocytaire circulante. L'evolution avait ete marquee par une hemorragie intracerebrale conduisant au deces du patient 7 mois apres le diagnostic. Conclusion Cette tendance hemorragique a ete rapportee a plusieurs reprises dans des cas de LCN. Cependant, les mecanismes physiopathologiques a l'origine des saignements ne sont pas encore completement elucides.

Published
2020

21. R‐DHA‐oxaliplatin (R‐DHAOx) versus R‐DHA‐cisplatin (R‐DHAP) regimen in B‐cell lymphoma treatment: A eight‐year trajectory study

Author

Jonathan Farhi, Mélanie Mercier, Valérie Seegers, Norbert Ifrah, Aline Tanguy-Schmidt, Mathilde Hunault-Berger, Sylvain Thepot, Marie-Pierre Moles, Carole Lacout, Aline Clavert, Manon De Vries, Corentin Orvain, Service des maladies du sang [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), 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), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, 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), and 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)

Subjects
Male, medicine.medical_specialty, Lymphoma, B-Cell, Clinical Decision-Making, [SDV.CAN]Life Sciences [q-bio]/Cancer, DHAP Regimen, Gastroenterology, Dexamethasone, Nephrotoxicity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, trajectories, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, platinum, Aged, Neoplasm Staging, Non-Hodgkin lymphoma, Cisplatin, Creatinine, business.industry, nephrotoxicity, Cytarabine, Disease Management, Hematology, General Medicine, Middle Aged, Survival Analysis, 3. Good health, Oxaliplatin, Regimen, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Disease Progression, Female, Kidney Diseases, Rituximab, business, 030215 immunology, medicine.drug
Abstract

International audience; Background: The R-DHAP regimen (rituximab, cisplatin, dexamethasone, and high-dose cytarabine) is standardly used to treat relapsed Non-Hodgkin lymphoma (NHL). Despite scarce data, cisplatin is frequently substituted with oxaliplatin (R-DHAOx) to avoid nephrotoxicity. We compared nephrotoxicity of cisplatin and oxaliplatin based on creatinine-based trajectory modeling.Methods: All patients with NHL treated by R-DHAP or R-DHAOx in Angers hospital between January 01, 2007, and December 31, 2014, were included. Patients received cisplatin 100 mg/m2 or oxaliplatin 130 mg/m2 (d1) with cytarabine (2000 mg/m2 , two doses, d2), dexamethasone (40 mg, d1-4), and rituximab (375 mg/m2 , d1). Creatinine levels were recorded before each cycle. Individual profiles of trajectories were clustered to detect homogeneous patterns of evolution.Results: Twenty-two patients received R-DHAP, 35 R-DHAOx, 6 switched from R-DHAP to R-DHAOx due to nephrotoxicity. Characteristics of patients were similar between two groups. Patients receiving R-DHAP experienced more severe renal injury than patients receiving R-DHAOx (68% vs. 7.7%, P < .001). Two homogeneous clusters appeared: cluster A, with a majority of R-DHAOx (32, 91.4%), was less nephrotoxic than B, with a majority of R-DHAP (19, 86.4%), with a decreased average serum creatinine level (P < .0001). There were no other differences between clusters.Conclusions: Our study confirms that R-DHAOx regimen causes less nephrotoxicity than R-DHAP regimen.

Published
2020

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

Author

Laurane Cottin, Sylvie Tondeur, Jean-Christophe Ianotto, Olivier Mansier, Lenaïg Le Clech, Jean-Marie Chrétien, Franciane Paul, Mélanie Mercier, Laurent Voillat, Dana Ranta, Benoit de Renzis, Olivier Allangba, François Girodon, Christophe Marzac, Mathilde Hunault-Berger, Valérie Ugo, Corentin Orvain, Driss Chaoui, Jérémie Riou, Eric Lippert, Bruno Cassinat, Jean-Jacques Kiladjian, Suzanne Tavitian, Françoise Boyer, Damien Luque Paz, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Biologie et Pathologie [CHU Grenoble] (IBP), CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hématologie Clinique [CHI Cornouaille, Quimper], Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' [Brest] (FHU GOAL), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie [CH Argenteuil], CH Argenteuil, Hématologie Clinique [CH Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), UFR Santé [UNIV Angers], Université d'Angers (UA), Laboratoire de Biologie Cellulaire [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cellule de Gestion des Données et Evaluation [CHU Angers] (DRCI - CGDE), Service d'hématologie clinique [CHRU de Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'Hématologie Clinique [CH Saint-Brieuc], Centre hospitalier Saint-Brieuc, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Chalon-sur-Saône William Morey, Service des maladies du sang [Angers], Service d'hématologie [Angers], Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Adult, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Long term follow up, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cohort Studies, 03 medical and health sciences, Exon, 0302 clinical medicine, Polycythemia vera, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Humans, article clinique, Polycythemia Vera, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Myeloproliferative Disorders, business.industry, Exons, Hematology, Janus Kinase 2, Middle Aged, Prognosis, medicine.disease, Survival Rate, Oncology, Mutation, Female, France, business, Follow-Up Studies, 030215 immunology
Abstract

International audience; No abstract available

Published
2020

23. Conditioning-based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991-2012) on behalf of EBMT CMWP

Author

Mauricette Michallet, Mathilde Hunault-Berger, Nicolaus Kröger, Jörg Cammenga, Johan Maertens, Monique C. Minnema, Jakob Passweg, Joan Hendrik Veelken, Riitta Niittyvuopio, Anja van Biezen, Stefan Schönland, Francisco José Márquez-Malaver, Simona Iacobelli, Arancha Bermúdez, Stéphanie Nguyen, Didier Blaise, Dietger Niederwieser, Ibrahim Yakoub-Agha, Noel Milpied, Patrick Hayden, Laurent Garderet, Yves Chalandon, Ellen Meijer, José Antonio Pérez-Simón, Jean Bourhis, 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), Hematology, CCA - Cancer Treatment and quality of life, AII - Inflammatory diseases, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)

Subjects
Male, History, Transplantation Conditioning, Graft vs Host Disease, Kaplan-Meier Estimate, 0302 clinical medicine, conditioning, hemic and lymphatic diseases, Retrospective analysis, ComputingMilieux_MISCELLANEOUS, ddc:616, Hematopoietic Stem Cell Transplantation, General Medicine, Hematology, Middle Aged, Prognosis, 20th Century, Settore MED/01, myeloma, Treatment Outcome, 030220 oncology & carcinogenesis, Retreatment, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Risk of death, Multiple Myeloma, CMWP, Autologous, Adult, Homologous, medicine.medical_specialty, Allogeneic transplantation, History, 21st Century, Transplantation, Autologous, EBMT, allogeneic transplantation, Aged, History, 20th Century, History, 21th Century, Humans, Proportional Hazards Models, Retrospective Studies, Transplantation, Homologous, 03 medical and health sciences, Internal medicine, Overall survival, medicine, Journal Article, In patient, Relapse risk, Autologous transplant, Transplantation, business.industry, Settore MED/15, 21th Century, Conditioning, business, 030215 immunology
Abstract

[Objectives] The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma—reduced intensity conditioning (RIC), non‐myeloablative (NMA), myeloablative conditioning (MAC) or Auto‐AlloHCT—on outcomes in patients who had had a prior autologous transplant., [Methods] A retrospective analysis of the EBMT database (1991‐2012) was performed., [Results] A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto‐Allo transplants. At a median follow‐up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%‐47%), 45% (95% CI 32%‐57%), 19% (95% CI 6%‐32%) and 34% (95% CI 17%‐51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276)., [Conclusion] From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.

Published
2020

24. Thromboembolism prophylaxis in adult patients with acute lymphoblastic leukemia treated in the GRAALL-2005 study

Author

Hervé Dombret, Patrice Chevallier, Jean-Pierre Marolleau, Jamile Frayfer, Nicolas Boissel, Emmanuelle Tavernier, Caroline Bonmati, Véronique Lhéritier, Mathilde Hunault-Berger, Marie Balsat, Denis Caillot, Yves Chalandon, Thomas Pabst, Norbert Ifrah, Sylvain Chantepie, Françoise Huguet, Noémie de Gunzburg, Corentin Orvain, Victoria Cacheux, 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), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Amiens-Picardie, Bern University Hospital [Berne] (Inselspital), Swiss Group for Clinical Cancer Research [Bern, Switzerland], Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier de Meaux, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), and Bernardo, Elizabeth

Subjects
Adult, Male, 0301 basic medicine, Asparaginase, medicine.medical_specialty, medicine.medical_treatment, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Acute lymphocytic leukemia, Internal medicine, Humans, Medicine, cardiovascular diseases, Neoadjuvant therapy, ddc:616, Heparin, business.industry, Incidence, Antithrombin, Fibrinogen, Induction Chemotherapy, Venous Thromboembolism, Cell Biology, Hematology, Thromboembolism Prophylaxis, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Thrombosis, 3. Good health, 030104 developmental biology, chemistry, Female, Fresh frozen plasma, business, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract

International audience; Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP). Antithrombin (AT) replacement has been suggested to prevent VTE and thus might increase exposure to ASP. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Between 2006 and 2014, 784 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 16% with 69% of them occurring during induction therapy. Most patients received AT supplementation (87%). After excluding patients who did not receive L-ASP or developed thrombosis before L-ASP, AT supplementation did not have a significant impact on VTE (8% versus 14%, OR: 0.6, p=0.1). Fibrinogen concentrates administration was associated with an increased risk of VTE (17% versus 9%, OR 2.2, p=0.02) whereas transfusion of fresh-frozen plasma had no effect. Heparin prophylaxis was associated with an increased risk of VTE (13% versus 7%, OR 1.9, p=0.04). Prophylactic measures were not associated with an increased risk of grade 3-4 bleeding complications. The rate of VTE recurrence after L-ASP reintroduction was 3% (1/34). In ALL patients receiving L-ASP therapy, the use of fibrinogen concentrates may increase the risk of thrombosis and should be restricted to rare patients with hypofibrinogenemia-induced hemorrhage. Patients developed VTE despite extensive AT supplementation which advocates for additional prophylactic measures. While this large descriptive study was not powered to demonstrate the efficacy of these prophylactic measures, it provides important insight to guide future trial design. NCT00327678.

Published
2020

25. Quantitative chimerism in CD3-negative mononuclear cells predicts prognosis in acute myeloid leukemia patients after hematopoietic stem cell transplantation

Author

Sylvie François, Mathilde Hunault-Berger, Bénédicte Ribourtout, Yves Delneste, Alban Villate, Laurane Cottin, Sylvain Thepot, Aurélien Sutra Del Galy, Damien Luque Paz, Odile Blanchet, Marie-Hélène Estienne, Valérie Ugo, Jérémie Riou, Corentin Orvain, Norbert Ifrah, Aline Schmidt, Anne Bouvier, Annaëlle Beucher, Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Innate immunity and Immunotherapy (CRCINA - Département INCIT - Equipe 7), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-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 de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-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 de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des maladies du sang [Angers], PRES Université Nantes Angers Le Mans (UNAM), Department of Hematology, CHU, Angers, Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'hématologie, Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), Hematology Department, Université d'Angers (UA), Laboratoire d'hématologie (Labo Hémato - ANGERS), 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), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, Neoplasm, Residual, CD3 Complex, medicine.medical_treatment, Cell, Hematopoietic stem cell transplantation, Disease, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Major complication, ComputingMilieux_MISCELLANEOUS, biology, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Prognosis, 3. Good health, Survival Rate, [STAT]Statistics [stat], Leukemia, Myeloid, Acute, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cohort, Female, Adult, medicine.medical_specialty, Adolescent, CD3, Chimerism, Peripheral blood mononuclear cell, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, Humans, Transplantation, Homologous, WT1 Proteins, Aged, Retrospective Studies, business.industry, 030104 developmental biology, biology.protein, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Relapse is a major complication of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (SCT). The objective of our study was to evaluate chimerism monitoring on the CD3-negative mononuclear cells by RQ-PCR to predict relapse of patients allografted for AML and to compare its performance with WT1 quantification. A cohort of 100 patients undergoing allogenic SCT for AML was retrospectively analyzed in a single institution. Patients without complete chimerism, defined as less than 0.01% of recipient’s DNA in CD3-negative cells, had a significantly higher risk of relapse and a lower overall survival (p

Published
2019

26. Sequential mutational evaluation of CALR ‐mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression

Author

Jean-Marie Chrétien, Odile Blanchet, Sophie Sadot-Lebouvier, Yves Delneste, Isabelle Quintin-Roué, Corentin Orvain, Olivier Mansier, Françoise Boyer, Barbara Burroni, Mathilde Hunault-Berger, Matgorzata Truchan-Graczyk, Damien Luque Paz, Maxime Renard, Marie-Christine Rousselet, Anne Murati, Jérémie Riou, Olivier Allangba, Laurane Cottin, Rébecca Jouanneau-Courville, Antoine Martin, Jean Christophe Ianotto, Valérie Ugo, Eric Lippert, Boullé, Christelle, Laboratoire d'hématologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service des maladies du sang [Angers], Département d'Hématologie Clinique (BREST - Hémato Clinique), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service des maladies du sang, Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), 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), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), 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), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Pathologie Cellulaire et Tissulaire [Angers] (Laboratoire d’Histopathologie-Cytopathologie), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), 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), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), CHU Cochin [AP-HP], Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), 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, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Oncology, Adult, Male, allele burden, medicine.medical_specialty, Myeloid, Adolescent, myeloproliferative neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, In patient, Allele, Myelofibrosis, CALR, Alleles, Aged, Aged, 80 and over, Thrombocytosis, Myeloproliferative Disorders, business.industry, Disease progression, High-Throughput Nucleotide Sequencing, Hematology, Middle Aged, medicine.disease, Prognosis, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cohort, Mutation, Disease Progression, Female, next-generation sequencing, Bone marrow, business, Calreticulin, 030215 immunology
Abstract

International audience; In myeloproliferative neoplasms (MPN), JAK2V617F allele burden measurement has an impact on prognosis that helps in patient monitoring. Less is known about its usefulness in CALR-mutated cases. Additional mutations found by next-generation sequencing have also shown an impact on prognosis that may drive therapeutic choices, especially in myelofibrosis, but few studies focused on CALR-mutated patients. We performed a molecular evaluation combining next-generation sequencing with a myeloid panel and CALR allele burden measurement at diagnosis and during follow-up in a cohort of 45 patients with CALR-mutated essential thrombocythaemia. The bone marrow histology was also blindly reviewed in order to apply the WHO2016 classification. The most frequently mutated gene was TET2 (11/21 mutations). CALR type 1-like patients appear to have a more complex molecular landscape. We found an association between disease progression and CALR allele burden increase during follow-up, independently of additional mutations and WHO2016-reviewed diagnosis. Patients with disease progression at the time of follow-up showed a significant increase in CALR allele burden (+16·7%, P = 0·005) whereas patients without disease progression had a stable allele burden (+3·7%, P = 0·194). This result argues for clinical interest in CALR allele burden monitoring.

Published
2019

27. Monitoring of asparagine depletion and anti-L-asparaginase antibodies in adult acute lymphoblastic leukemia treated in the pediatric-inspired GRAALL-2005 trial

Author

Mathilde Hunault-Berger, Xavier Thomas, Véronique Lhéritier, Norbert Ifrah, Christine Vianey-Saban, Hervé Dombret, Cécile Acquaviva-Bourdain, Thibaut Leguay, Jérôme Paillassa, Marie Audrain, Cécile Pagan, Nicolas Boissel, Françoise Huguet, Innate immunity and Immunotherapy ( CRCINA - Département INCIT - Equipe 7 ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -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 ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service des maladies du sang [Angers], CHU Angers, Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d’Hématologie Clinique [CHU de Lyon], CHU de Lyon, Service d’hématologie Clinique [CHU Toulouse], CHU Toulouse [Toulouse], Laboratoire d'Immunologie [CHU Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Coordination du Groupe GRAALL [CH Lyon-Sud], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] ( Centre de Biologie et Pathologie Est ), Hospices Civils de Lyon ( HCL ) -Groupement Hospitalier Est, Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] ( ORS PACA ), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Bernardo, Elizabeth

Subjects
Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology, lcsh:RC254-282, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, L asparaginase, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Isoantibodies, Correspondence, Medicine, Asparaginase, Humans, Asparagine, Child, ComputingMilieux_MISCELLANEOUS, biology, business.industry, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Clinical trial, Oncology, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Adult Acute Lymphoblastic Leukemia, biology.protein, Female, Antibody, business, 030215 immunology
Abstract

International audience; no abstract

Published
2018

28. Allogeneic stem cell transplantation recipients requiring intensive care: time is of the essence

Author

Aline Tanguy-Schmidt, Sylvie François, Sylvain Thepot, Corentin Orvain, Mathilde Hunault-Berger, Pierre Asfar, Mélanie Mercier, Norbert Ifrah, Jean-François Hamel, François Beloncle, Jonathan Farhi, Aurélien Sutra Del Galy, Alain Mercat, Achille Kouatchet, 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 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), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Réanimation Médicale [CHU Angers], Centre de Recherche Clinique (CRC Angers), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Bernardo, Elizabeth, 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), Innate immunity and Immunotherapy ( CRCINA - Département INCIT - Equipe 7 ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -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 ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), CHU Angers, Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] ( FHU GOAL ), Centre hospitalier universitaire d'Angers ( CHU Angers ), Centre de Recherche Clinique ( CRC Angers ), and Université d'Angers ( UA ) -CHU Angers

Subjects
Adult, Male, Intensive care unit (ICU), medicine.medical_specialty, Time Factors, Critical Care, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Early admission, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Refractory, law, Risk Factors, Intensive care, medicine, Humans, Transplantation, Homologous, Hospital Mortality, Retrospective Studies, business.industry, Mortality rate, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, General Medicine, Middle Aged, Intensive care unit, Lymphoproliferative Disorders, 3. Good health, Transplantation, Hospitalization, Intensive Care Units, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Emergency medicine, Allogeneic stem cell transplantation (SCT), Female, Stem cell, business, 030215 immunology
Abstract

International audience; The benefit of early admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) as soon as they develop organ injury is unknown. We performed a retrospective study on 92 patients admitted to the ICU to determine the impact of time from organ injury to ICU admission on outcome. The number of organ injuries prior to ICU admission was associated with an increased in-hospital mortality (OR 1.7, 95% CI 1–2.7, p = 0.04). Time between first organ injury and ICU admission was also associated with an increased in-hospital survival (OR 1.4, 95% CI 1.1–1.8, p = 0.02). A score combining these two covariates—the number of organ injuries/day (sum of days spent with each individual organ injury)—further improved the prediction of hospital survival. Patients with more organ injuries/day had significantly higher in-hospital mortality rate even after adjustment for refractory acute GVHD and the SOFA (OR 1.3, 95% CI 1–1.7, p = 0.02). Early ICU admission of allogeneic SCT recipients to the ICU as soon as they develop organ injury is associated with decreased in-hospital mortality.

Published
2018

29. Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Gérard Socié, Jan J. Cornelissen, Patrice Chevallier, Didier Blaise, Nigel H. Russell, Mauricette Michallet, Mathilde Hunault-Berger, Charles Craddock, Jakob Passweg, Xavier Poiré, Myriam Labopin, Arnon Nagler, Jordi Esteve, Emmanuelle Polge, Liisa Volin, Nathalie Fegueux, Arne Brecht, Mohamad Mohty, UCL - (SLuc) Département de médecine interne et services associés, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Hematology, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre 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), Clinicum, Department of Oncology, Hematologian yksikkö, and HUS Comprehensive Cancer Center

Subjects
medicine.medical_specialty, Allogeneic transplantation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], PROGNOSTIC IMPACT, 3122 Cancers, Hematopoietic stem cell transplantation, HEMATOLOGIC MALIGNANCIES, GERIATRIC ASSESSMENT, 03 medical and health sciences, ALLELIC RATIO, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Survival rate, SORAFENIB MAINTENANCE, Acute leukemia, ACUTE MYELOGENOUS LEUKEMIA, OLDER PATIENTS, business.industry, Myeloid leukemia, 1ST COMPLETE REMISSION, Hematology, medicine.disease, CYTOGENETICALLY NORMAL AML, 3. Good health, Transplantation, Leukemia, NPM1 MUTATIONS, 030220 oncology & carcinogenesis, Fms-Like Tyrosine Kinase 3, business, 030215 immunology
Abstract

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (P= 60 with FLT3-ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients.

Published
2017

30. 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

31. Circulating Cd34+ cell count differentiates primary myelofibrosis from other Philadelphia-negative myeloproliferative neoplasms:a pragmatic study

Author

Mathilde Hunault-Berger, Jean-Christophe Ianotto, Norbert Ifrah, Aurélie Chauveau, Irène Dobo, D. Luque Paz, Jonathan Farhi, Françoise Boyer, B. Guibourg, Franck Geneviève, Marie-Christine Rousselet, Marc Zandecki, Valérie Ugo, G. Le Calvez, Laurane Cottin, Mélanie Mercier, Corentin Orvain, 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), Laboratoire d'hématologie, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang, Université d'Angers (UA), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Bernardo, Elizabeth

Subjects
0301 basic medicine, medicine.medical_specialty, Pathology, Cd34 cells, DNA Mutational Analysis, CD34, Antigens, CD34, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Myelofibrosis, Myeloproliferative neoplasm, Retrospective Studies, Philadelphia negative, Myeloproliferative Disorders, Hematology, Janus kinase 2, biology, business.industry, Area under the curve, General Medicine, Janus Kinase 2, Hematopoietic Stem Cells, medicine.disease, Blood Cell Count, 3. Good health, 030104 developmental biology, ROC Curve, Primary Myelofibrosis, Area Under Curve, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Mutation, biology.protein, Calreticulin, business, Receptors, Thrombopoietin
Abstract

International audience; A high number of circulating CD34+ cells has been advocated to distinguish primary myelofibrosis from other Philadelphia-negative myeloproliferative neoplasms. We reevaluated the diagnostic interest of measuring circulating CD34+ cells in 26 healthy volunteers and 256 consecutive patients at diagnosis for whom a myeloproliferative neoplasm was suspected. The ROC curve analysis showed that a number of CD34+

Published
2016

32. Prevention of Venous Thrombotic Events in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatric-Inspired Protocol - a Graall Study

Author

Emmanuelle Tavernier, Denis Caillot, Yves Chalandon, Sylvain Chantepie, Françoise Huguet, Thomas Pabst, Norbert Ifrah, Corentin Orvain, Nicolas Boissel, Hervé Dombret, Patrice Chevallier, Marie Balsat, Mathilde Hunault-Berger, Véronique Lhéritier, Jamile Frayfer, Victoria Cacheux, Noémie de Gunzburg, Jean-Pierre Marolleau, Caroline Bonmati, 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), Laboratoire d'hématologie, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Amiens-Picardie, Inselspital Bern, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier de Meaux, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), PRES Université Nantes Angers Le Mans (UNAM), and DESSAIVRE, Louise

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, business.industry, Cell Biology, Hematology, Odds ratio, medicine.disease, Thrombosis, Surgery, Discontinuation, Pulmonary embolism, Transplantation, [SDV] Life Sciences [q-bio], Venous thrombosis, Platelet transfusion, 030220 oncology & carcinogenesis, Fresh frozen plasma, business
Abstract

Background: Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP) and subsequent antithrombine (AT) deficiency. Previous reports showed that patients with venous thrombotic events (VTE) have a lower event-free survival that may be due to early discontinuation of L-ASP. It has been suggested that AT replacement could decrease the rate of thrombosis and prevent L-ASP discontinuation. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Methods: All patients received a 5-drug induction therapy with 8 native E. Coli-ASP intravenous injections (6,000 UI/m2/injection). Patients in complete remission (CR) received two consolidation courses each containing two L-ASP intravenous injections (10000 UI/m2/injection). All patients in persistent CR for whom allogeneic stem cell transplantation was not indicated in first CR received a late intensification with the same drugs as in the induction course, followed by the repetition of one consolidation course. Platelet transfusion support was recommended for platelets below 20 x 109/L, fresh frozen plasma (FFP) or fibrinogen concentrates were recommended if fibrinogen levels fell below 0.5 g/L, and AT concentrate substitution therapy was recommended in order to maintain AT levels above 60%. Prophylactic heparin was recommended during induction and late intensification. All cases of VTE were identified prospectively by clinical signs and confirmed by radiological imaging based on institutional guidelines. Results: Between 2006 and 2014, 787 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 14.4% (113 VTEs in 110 patients). VTEs included 72 (64%) deep vein thromboses (DVT), with one third in the lower limb and two thirds in the upper limb, 32 (28%) cerebral venous thrombosis (CVT), and 13 (12%) pulmonary embolism (PE). No disease characteristic was associated with a higher risk of thrombosis. Patients with DVT and/or PE were older (median age of 40 versus 38 for those with CVT versus 35 for those without VTE, p=0.04), had a higher BMI (median BMI of 26 versus 23 for those with CVT and 24 for those without VTE, p=0.01), and had a higher platelet count at diagnosis (median platelet count of 100 G/l versus 84 G/l for those with CVT versus 68 G/l for those without VTE, p=0.06) whereas patients with CVT had higher hemoglobin levels (median hemoglobin level of 11.7 g/dl versus 10.1 g/dl for those with DVT/PE versus 10.2 g/dl for those without VTE, p=0.03). Sixty-seven percent of VTEs occurred during induction therapy. Other VTEs occurred as follows: 17 (15%) during consolidation phase 1 (688 patients), 4 (4%) during consolidation phase 2 (537 patients), 9 (8%) during late intensification (356 patients), and 7 (6%) in 335 during consolidation phase 3 (335 patients). The type of thrombosis was different according to treatment phase as most CVT occurred during induction therapy (29 versus 3 CVTs during subsequent phases of treatment, p=0.003). During induction therapy, patients with VTE were more likely to have received heparin prophylaxis (82% versus 60% for those without VTE, odds ratio (OR) 1.8, p=0.06) and fibrinogen prophylaxis (14% versus 8% for those without VTE, OR 2, p=0.05) whereas they received less AT prophylaxis (82% versus 88% for those without VTE, OR 0.5, p=0.05). Patients with VTE received less L-ASP infusions during induction therapy (median number of 7 versus 8 injections for those without VTE, p Conclusion: In ALL patients receiving L-ASP therapy, appropriate AT prophylaxis was associated with less VTE and should be used extensively. Maintaining higher AT levels in patients at increased risk for VTE should be evaluated. L-ASP can be reintroduced in patients who experienced VTE during induction as none had thrombotic recurrence. Fibrinogen concentrates may increase the risk of thrombosis and should be restricted to patients with hemorrhage. Disclosures Dombret: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Published
2016

33. Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis

Author

S. François, J. F. Hamel, Norbert Ifrah, Aline Tanguy-Schmidt, F. Moal, Mélanie Mercier, Corentin Orvain, Mathilde Hunault-Berger, M. P. Moles-Moreau, E. Parot-Schinkel, Service des maladies du sang [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), 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), and Bernardo, Elizabeth

Subjects
Adult, Male, Mucositis, medicine.medical_specialty, Antifungal Agents, Adolescent, Miconazole, Analgesic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Gastroenterology, Young Adult, Autologous stem-cell transplantation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Amphotericin B, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, Aged, Stomatitis, business.industry, Hematopoietic Stem Cell Transplantation, Induction chemotherapy, Induction Chemotherapy, Buccal administration, Middle Aged, medicine.disease, 3. Good health, Surgery, Transplantation, Treatment Outcome, Oncology, Female, Multiple Myeloma, business, Tablets, medicine.drug
Abstract

International audience; Oral mucositis is a major cause of morbidity in high-dose therapy/autologous stem cell transplantation (HDT/ASCT), where microbial colonization has an important pathological implication. In this study, we evaluated the impact of miconazole mucoadhesive buccal tablet (MBT) on mucositis-related complications. During two consecutive 34-month periods, patients treated with HDT/ASCT in our hematology department received either miconazole MBT (60 patients) or conventional oral amphotericin B suspensions three times a day (44 patients) in order to prevent or decrease chemotherapy-induced mucositis. The use of miconazole MBT is associated with less infectious complications as indicated by shorter antibiotic use (7.8 vs. 12.3 days; p < 0.0001), shorter intravenous antifungal use (1.4 vs. 3.6 days; p = 0.02), and a trend towards less yeast contamination in stool samples. Less patients required any analgesic drugs during hospitalization in the miconazole MBT group (18 vs. 7 %; p = 0.09). Indirect indicators of chemotherapy-induced mucositis (duration of hospitalization, morphine use) were in favor of miconazole MBT in patients with multiple myeloma (MM) but not for those with lymphoma. This study suggests that miconazole MBT provides a valid alternative to oral amphotericin B suspensions in regards to mucositis-related complications. A prospective and randomized study is warranted to establish the definite role of miconazole MBT.

Published
2015

34. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

Author

Emmanuelle Nicolas-Virelizier, Emmanuel Gyan, Peggy Dartigues, Serge Bologna, Florence Broussais-Guillaumot, Emmanuel Bachy, Julien Lazarovici, Marc André, Mathilde Hunault-Berger, Jean Gabarre, Christophe Fermé, Pauline Brice, Richard Delarue, Luc-Matthieu Fornecker, Olivier Casasnovas, Virginie Roland, Thomas Gastinne, Aspasia Stamatoullas, Isabelle Gaillard, Frédérique Orsini-Piocelle, Lucie Oberic, Nicolas Mounier, Frederic Peyrade, Mohamed Touati, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Unité des hémopathies lymphoïdes [CHU Henri Mondor], CHU Henri Mondor, 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 des maladies du sang [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie et thérapie cellulaire [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [CH Annecy], CH Annecy, Département d’Hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre hospitalier universitaire de Nantes (CHU Nantes), Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service d'Hématologie [CH Perpignan], CH Perpignan, CHU Dinant-Godinne UCL Namur [Yvoir, Belgique], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut Gustave Roussy ( IGR ), Laboratoire de Psychologie et NeuroCognition ( LPNC ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Grenoble Alpes ( UGA ), 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 ), Centre d'Etude et de Recherche Travail Organisation Pouvoir ( CERTOP ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Institut national universitaire Champollion - Albi ( INU Champollion ), 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 d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), CIC - Tours, CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Orange Labs [Paris], Telecom Orange, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CRLCC Henri Becquerel, Service d'Hématologie Clinique [Nantes] ( Unité d'Investigation Clinique ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, AGROCAMPUS OUEST, Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS 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 ), Swedish Institute of Space Physics [Uppsala] ( IRF ), Bernardo, Elizabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Models, Biological, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, Risk Factors, Internal medicine, hemic and lymphatic diseases, Medicine, Humans, education, Survival rate, Retrospective Studies, Aged, education.field_of_study, Chemotherapy, business.industry, Hazard ratio, Articles, Hematology, Middle Aged, medicine.disease, Combined Modality Therapy, Hodgkin Disease, 3. Good health, Surgery, Lymphoma, Radiation therapy, Survival Rate, Rituximab, Female, business, Watchful waiting, medicine.drug
Abstract

International audience; Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320-1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234-0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.

Published
2015

35. Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples

Author

Yves Delneste, Norbert Ifrah, Diane Raingeard de la Blétière, Mathilde Hunault-Berger, Marc Zandecki, Anne Coutolleau, Isabelle Luquet, Philippe Guardiola, Laurence Baranger, Pascale Cornillet-Lefebvre, Annaëlle Beucher, Odile Blanchet, Aline Schmidt-Tanguy, Franck Geneviève, BMC, Ed., Plateforme SNP, Transcriptome & Epigénomique, 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 Nantes-Angers (CRCNA), 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), Laboratoire d'hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de génétique, Service des maladies du sang, and PhG from Plateforme SNP, Transcriptome & Epigénomique received a grant from La Ligue Contre le Cancer/Comité Départemental 49 to support this work.

Subjects
Adult, Male, Quality Control, Acute promyelocytic leukemia, lcsh:Internal medicine, Myeloid, lcsh:QH426-470, Adolescent, Microarray, Biology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, hemic and lymphatic diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Humans, Genetics(clinical), Genetic Predisposition to Disease, lcsh:RC31-1245, Genetics (clinical), Aged, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Gene Expression Profiling, Myeloid leukemia, Middle Aged, medicine.disease, Confidence interval, Gene expression profiling, lcsh:Genetics, Leukemia, Myeloid, Acute, Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Immunology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, DNA microarray, Research Article
Abstract

Background Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n = 101) and/or poor quality control criteria (n = 10) (test set). Results With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.

Published
2012

36. Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms

Author

David Jérémie Birnbaum, Catherine Lacombe, Michaela Fontenay, Norbert Vey, L Slama, Mathilde Hunault-Berger, Francois Dreyfus, Odile Beyne-Rauzy, Borhane Slama, Eric Solary, Véronique Gelsi-Boyer, Olivier Kosmider, Olivier A. Bernard, Bruno Quesnel, Service greffe de moelle osseuse, 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), Université Pierre et Marie Curie - Paris 6 (UPMC), Groupe français des myéloplastes and groupe ouest est des leucemies aigües myéloïde (SERVICE DES MALADIES DU SANG), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Cancer Research, IDH1, Molecular Sequence Data, Biology, IDH2, Dioxygenases, 03 medical and health sciences, 0302 clinical medicine, Proto-Oncogene Proteins, hemic and lymphatic diseases, medicine, Humans, Base sequence, Gene, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, Aged, 80 and over, Genetics, 0303 health sciences, Myeloproliferative Disorders, Base Sequence, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Myelodysplastic syndromes, Hematology, Janus Kinase 2, Middle Aged, medicine.disease, Isocitrate Dehydrogenase, 3. Good health, DNA-Binding Proteins, Oncology, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Mutation
Abstract

Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms

Published
2010

37. The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients

Author

Richard Delarue, Mathilde Hunault-Berger, Olivier Tournilhac, Arnaud Jaccard, Philippe Rodon, Pierre Morel, Marc Bernard, Arnaud Hot, Mohamed Hamidou, Benjamin Terrier, Fadi Fakhouri, Olivier Gisserot, Jean-Paul Fermand, Bernard Grosbois, Caroline Elie, Jacques Dantal, Véronique Leblond, Valérie Coiteux, Jean-Luc Harousseau, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, 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), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation et de recherche en transplantation (ITERT), Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Laboratoire de physique des milieux ionisés et applications (LPMIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de médecine interne, Physique des milieux ionisés et applications (LPMIA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ITUN, Institut de transplantation et de recherche en transplantation ( ITERT ), Laboratoire Hubert Curien [Saint Etienne] ( LHC ), Institut d'Optique Graduate School ( IOGS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des milieux ionisés et applications ( LPMIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP)

Subjects
Male, Pathology, MESH: Remission Induction, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, MESH : Alkylating Agents, MESH: Antigens, CD20, Hematopoietic stem cell transplantation, Gastroenterology, MESH: Antibodies, Monoclonal, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Treatment Outcome, Aged, 80 and over, MESH: Middle Aged, MESH: Heart Diseases, Amyloidosis, MESH: Immunologic Factors, Remission Induction, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, General Medicine, MESH: Immunoglobulin M, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, MESH : Paraproteinemias, Rituximab, medicine.medical_specialty, Alkylating Agents, MESH: Serum Albumin, 03 medical and health sciences, MESH: Lymphatic Diseases, MESH : Antigens, CD20, MESH : Hematopoietic Stem Cell Transplantation, AL amyloidosis, Humans, Immunologic Factors, MESH : Middle Aged, MESH : Aged, 80 and over, Lymphatic Diseases, Aged, Retrospective Studies, MESH: Humans, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Amyloidosis, Complication, MESH: Female, Lung Diseases, Paraproteinemias, Antibodies, Monoclonal, Murine-Derived, MESH: Lung Diseases, MESH: Paraproteinemias, MESH: Aged, 80 and over, MESH : Purines, MESH : Female, Prospective cohort study, MESH: Aged, MESH : Lung Diseases, MESH : Lymphatic Diseases, MESH: Purines, Middle Aged, MESH : Adult, MESH : Survival Rate, Hematologic Response, MESH: Alkylating Agents, Treatment Outcome, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, medicine.drug, Adult, Heart Diseases, MESH: Survival Rate, MESH : Immunoglobulin M, MESH : Male, MESH : Treatment Outcome, MESH : Immunologic Factors, MESH : Serum Albumin, Internal medicine, medicine, MESH: Amyloidosis, MESH : France, Serum Albumin, MESH: Hematopoietic Stem Cell Transplantation, MESH : Remission Induction, business.industry, Retrospective cohort study, MESH : Heart Diseases, Antigens, CD20, MESH: Male, MESH: France, Immunoglobulin M, Purines, business, 030215 immunology
Abstract

International audience; Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known complication of monoclonal IgM-associated disorders. We sought to determine the clinical and laboratory presentation, response to treatment, and outcome of patients with IgM-related amyloidosis in the era of new therapeutic approaches. We conducted a retrospective study in 29 French centers to identify patients with monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and collected relevant clinical and laboratory data. We identified 72 patients with IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64, peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A peculiar pattern of relatively frequent lymph node (31%) and lung (17%) involvement was noted in patients with systemic AL amyloidosis. Response to alkylating agents was poor, with a hematologic response in 37%, a complete remission in 0%, and an organ response in 21%. Response to hematopoietic stem cell transplantation showed a hematologic response in 100% with complete remission in 75% and an organ response in 75%. Purine analogs and rituximab induced a hematologic response in 73% and 60%, respectively, with complete remission in 9% and 0% and an organ response in 55% and 0%, respectively. In multivariate analysis, prognostic factors for survival were serum albumin level < or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective studies are needed in patients with IgM-related amyloidosis, with special emphasis on treatment options: hematopoietic stem cell transplantation and purine analogs could represent the most effective therapies. The identification of adverse prognostic factors of survival could be useful for those managing and making treatment decisions for these patients.

Published
2008

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