Author: "Mathilde Hunault-Berger" / Publication Year Range: Last 50 years - Searchworks@Jio Institute Digital Library Search Results

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137 results on '"Mathilde Hunault-Berger"'

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

Author: Mélanie Mercier, Corentin Orvain, Laurianne Drieu La Rochelle, Tony Marchand, Christopher Nunes Gomes, Aurélien Giltat, Jérôme Paillassa, Aline Clavert, Jonathan Farhi, Marie-Christine Rousselet, Emmanuel Gyan, Roch Houot, Marie-Pierre Moles-Moreau, and Mathilde Hunault-Berger
Subjects: lymphoma, bone, skeletal, high-dose methotrexate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
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 < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p p < 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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6. 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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7. 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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8. 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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9. 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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10. Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report

Author: Cabannes-Hamy, Aurelie, primary, Courtois, Lucien, additional, Balsat, Marie, additional, Simonin, Mathieu, additional, Huguet, Françoise, additional, Escoffre-Barbe, Martine, additional, Pasquier, Florence, additional, Bonmati, Caroline, additional, Turlure, Pascal, additional, Cluzeau, Thomas, additional, Lebon, Delphine, additional, Gehlkopf, Eve, additional, Brissot, Eolia, additional, Decroocq, Justine, additional, Chevallier, Patrice, additional, Chantepie, Sylvain, additional, Cacheux, Victoria, additional, Maury, Sebastien, additional, Chebrek, Safia, additional, Leguay, Thibaut, additional, Fort, Melody, additional, Mauz, Natacha, additional, Lamarque, Mathlide, additional, Mathilde, Hunault-Berger, additional, Wickenhauser, Stefan, additional, Frayfer, Jamilé, additional, Banos, Anne, additional, Tavernier, Emmanuelle, additional, Caillot, Denis, additional, Ronchetti, Anne Marie, additional, Berthon, Celine, additional, Lengline, Etienne, additional, Lhéritier, Véronique, additional, Dombret, Hervé, additional, Marçais, Ambroise, additional, Pinton, Antoine, additional, Andrieu, Guillaume P, additional, Boissel, Nicolas, additional, Lhermitte, Ludovic, additional, Asnafi, Vahid, additional, and Rousselot, Philippe, additional
Published: 2023
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11. Implementation of a new blood cultures sampling strategy in patients receiving intensive chemotherapy for acute leukemia and/or hematopoietic cell transplantation

Author: Charles Declerck, Aurélien Giltat, Romane Boutemy, Marie Brisset-Dheilly, Anais Pelhatre, Mathilde Hunault-Berger, Marie Kempf, Achille Kouatchet, Raphael Mahieu, Aline Tanguy-Schmidt, and Corentin Orvain
Subjects: Cancer Research, Oncology, Hematology
Published: 2023

12. Outcome of patients with newly diagnosed AML admitted to the ICU, including preemptive admission – a multi-center study

Author: Christophe Desprez, Achille Kouatchet, Tony Marchand, Jean Baptiste Mear, Jean Marc Tadié, Pierre Peterlin, Patrice Chevalier, Emmanuel Canet, Marie-Anne Couturier, Gaelle Guillerm, Laetitia Bodenes, Emmanuel Gyan, Alban Villate, Stephan Ehrmann, Anne Lebreton, Marie-Antoinette Lester, Clémentine Fronteau, Gaelle Larhantec, Virginie André, Jérémie Riou, Mathilde Hunault-Berger, Aline Schmidt-Tanguy, and Corentin Orvain
Subjects: Hematology, General Medicine
Published: 2023

13. Relationship between comorbidities, mutational profile, and outcome after intensive chemotherapy in patients older than 60 years with acute myeloid leukemia: Assessment of different risk scores

Author: Amélie Bachelot, Anne Bouvier, Jérémie Riou, Sylvain Thepot, Aurélien Giltat, Christopher Nunes Gomes, Jérôme Paillassa, Rébecca Jouanneau‐Courville, Maxime Renard, Annaelle Beucher, Laurane Cottin, Margaux Wiber, Bénédicte Ribourtout, Franck Geneviève, Damien Luque Paz, Aline Tanguy‐Schmidt, Valérie Ugo, Mathilde Hunault‐Berger, Odile Blanchet, and Corentin Orvain
Subjects: Hematology
Published: 2023

14. Outcomes after allogeneic hematopoietic cell transplant in patients diagnosed with blast phase of myeloproliferative neoplasms: A retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Author: Guillermo Ortí, Luuk Gras, Nienke Zinger, Maria Chiara Finazzi, Katja Sockel, Marie Robin, Edouard Forcade, Daniele Avenoso, Nicolaus Kröger, Jürgen Finke, Aleksandar Radujkovic, Mathilde Hunault‐Berger, Wilfried Schroyens, Tsila Zuckerman, Jean Henri Bourhis, Yves Chalandon, Adrian Bloor, Rik Schots, Liesbeth C. de Wreede, Joana Drozd‐Sokolowska, Kavita Raj, Nicola Polverelli, Tomasz Czerw, Juan Carlos Hernández‐Boluda, Donal McLornan, Ibrahim Yakoub‐Agha, Brussels Heritage Lab, Clinical sciences, and Hematology
Subjects: surgery, allogeneic hematopoietic cell transplant, Chronic Malignancies Working Party, retrospective study, oncology, outcome, blast phase of myeloproliferative neoplasms, European Society for Blood and Marrow Transplantation, Human medicine, Hematology, transplantation
Abstract: Allogeneic hematopoietic cell transplant (allo-HCT) provides the only potential route to long-term remission in patients diagnosed with blast phase transformation of mye-loproliferative neoplasm (BP-MPN). We report on a large, retrospective European Society for Blood and Marrow Transplantation registry-based study of BP-MPN patients undergoing allo-HCT. BP-MPN patients undergoing first allo-HCT between 2005 and 2019 were included. A total of 663 patients were included. With a median follow-up of 62 months, the estimated 3-year overall survival (OS) was 36% (95% confidence interval [CI], 32-36). Factors associated with lower OS were Karnofsky Performance Score (KPS) < 90 (hazard ratio [HR] 1.65, p < .001) and active disease at allo-HCT (HR 1.45, p < .001), whereas patients undergoing allo-HCT more recently associated with a higher OS (HR 0.96, p = .008). In a selected patient's population, the 3-year OS of patients undergoing allo-HCT in complete response (CR) and with a KPS >= 90 was 60%. KPS < 90 (HR 1.4, p = .001) and active disease (HR 1.44, p = .0004) were associated with a lower progression-free survival (PFS). Conversely, most recent allo-HCT associated with a higher PFS (HR 0.96, p = .008). Active dis-ease at allo-HCT (HR 1.34, p = .03) was associated with a higher cumulative inci-dence of relapse (RI) and allo-HCT in earlier calendar years (HR 0.96, p = .02) associated with a lower RI. Last, KPS < 90 (HR 1.91, p < .001), active disease (HR 1.74, p = .003) and allo-HCT from mismatched related donors were associated with a higher non-relapse mortality (HR 2.66, p = .003). In this large series of BPMPN patients, about one third were alive at 3 years after transplantation. Patients undergoing allo-HCT in the more recent era, with a KPS >= 90 and in CR at transplant had a better prognosis.
Published: 2023

15. The conjunction of uncommon diagnoses: a case report of concomitant lymphomatoid granulomatosis and pulmonary tuberculosis

Author: Nicolas Giachetti, Sarah Bellal, Marianne Schwarz, Jérôme Paillassa, Aline Clavert, Mathilde Hunault-Berger, and Firas Safa
Abstract: Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible with the disease. Lymphatic involvement is uncommon. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis in an elderly woman. Case presentation: An 80-year-old woman presented to the emergency unit for steadily increasing dyspnea, with a workup revealing bilateral nodules and mediastinal lymph node enlargement on chest imaging, associated with a mildly elevated C-reactive protein (CRP). She had no relevant prior medical history and no known immunodepression. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined to azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade I lymphomatoid granulomatosis. Treatment with corticosteroids and weekly rituximab was initiated, leading to a rapid improvement of respiratory symptoms. After the second dose of rituximab, initially collected sputum cultures were found positive for Mycobacterium tuberculosis. Rituximab was suspended and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both infectious and hematological diseases with at least a partial remission of the lymphomatoid granulomatosis. Conclusions: This case report highlights both diagnosis and therapeutic challenges in a rare but plausible situation. Lymph-node involvement in lymphomatoid granulomatosis should always be questioned in LYG as it is seldom seen in the disease. Finally, pathologic confirmation for LYG should not eliminate the need for a comprehensive workup to eliminate other differential diagnoses with management-changing potential.
Published: 2023

16. 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

17. 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, primary, Bertoli, Sarah, additional, Peterlin, Pierre, additional, Guieze, Romain, additional, Desbrosses, Yohan, additional, Hicheri, Yosr, additional, Benbrahim, Omar, additional, Carre, Martin, additional, Mathilde, Hunault-Berger, additional, Banos, Anne, additional, Bernard, Marc, additional, Gyan, Emmanuel, additional, Saad, Alain, additional, Chebrek, Safia, additional, Roth Guepin, Gabrielle, additional, Dorvaux, Veronique, additional, Sanhes, Laurence, additional, Gallego Hernanz, Maria Pilar, additional, Exbrayat, Carole, additional, Vincent, Laure, additional, Himberlin, Chantal, additional, Largeaud, Laetitia, additional, Delabesse, Eric, additional, Vergez, Francois, additional, Vey, Norbert, additional, Mineur, Ariane C, additional, Simand, Célestine, additional, Luquet, Isabelle, additional, and Pigneux, Arnaud, additional
Published: 2022
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18. 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, primary, Eikema, Dirk-Jan, additional, Zinger, Nienke, additional, Platzbecker, Uwe, additional, Sockel, Katja, additional, Finke, Jürgen, additional, Kröger, Nicolaus, additional, Forcade, Edouard, additional, Nagler, Arnon, additional, Ganser, Arnold, additional, Tischer, Johanna, additional, Broers, Annoek E.C., additional, Kuball, Jurgen, additional, Wilson, Keith, additional, Mathilde, Hunault-Berger, additional, Collin, Matthew P., additional, Russo, Domenico, additional, Pérez López, Estefanía, additional, Helbig, Grzegorz, additional, Mussetti, Alberto, additional, Raj, Kavita, additional, Scheid, Christof, additional, McLornan, Donal P., additional, Robin, Marie, additional, and Yakoub-Agha, Ibrahim, additional
Published: 2022
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19. 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, primary, Huguet, Francoise, additional, Leguay, Thibaut, additional, Mathilde, Hunault-Berger, additional, Graux, Carlos, additional, Chalandon, Yves, additional, Delabesse, Eric, additional, Hicheri, Yosr, additional, Chevallier, Patrice, additional, Balsat, Marie, additional, Pastoret, Cedric, additional, Escoffre-Barbe, Martine, additional, Pasquier, Florence, additional, Marolleau, Jean-Pierre, additional, Thiebaut-Bertrand, Anne, additional, Huynh, Anne, additional, Dhedin, Nathalie, additional, Lemasle, Emilie, additional, Bonmati, Caroline, additional, Maury, Sébastien, additional, Guillerm, Gaëlle, additional, Berceanu, Anna, additional, Schanz, Urs, additional, Cluzeau, Thomas, additional, Turlure, Pascal, additional, Rousselot, Philippe, additional, De Prijck, Bernard J.M., additional, Grardel, Nathalie, additional, Bene, Marie C, additional, Lafage, Marine, additional, Ifrah, Norbert, additional, Lheritier, Veronique, additional, Asnafi, Vahid, additional, Clappier, Emmanuelle, additional, and Dombret, Herve, additional
Published: 2022
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20. Different number of circulating CD34 + cells in essential thrombocythemia, prefibrotic/early primary myelofibrosis, and overt primary myelofibrosis

Author: Valérie Ugo, Marie-Christine Rousselet, Damien Luque Paz, Laurane Cottin, Eric Lippert, Barbara Burroni, Françoise Boyer, Corentin Orvain, Franck Geneviève, Jean-Christophe Ianotto, Jean-Baptiste Robin, Charles Bescond, Mathilde Hunault-Berger, Isabelle Quintin-Roué, 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-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), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], Département d'anatomopathologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and LUQUE PAZ, DAMIEN
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, medicine.medical_specialty, Hematology, Primary (chemistry), business.industry, Essential thrombocythemia, Cd34 cells, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, medicine.disease, Polycythemia vera, Bone Marrow, Primary Myelofibrosis, Internal medicine, medicine, Humans, Myeloproliferative Neoplasms, Essential Thrombocythemia, business, Myelofibrosis, ComputingMilieux_MISCELLANEOUS, Thrombocythemia, Essential
Abstract: International audience; No abstract available
Published: 2021

21. Outcomes after Allogeneic Hematopoietic Cell Transplant in patients diagnosed with Blast Phase of Myeloproliferative Neoplasms: a retrospective study from the Chronic Malignancies Working Party of the EBMT

Author: Guillermo, Ortí, Luuk, Gras, Nienke, Zinger, Maria Chiara, Finazzi, Katja, Sockel, Marie, Robin, Edouard, Forcade, Daniele, Avenoso, Nicolaus, Kröger, Jürgen, Finke, Aleksandar, Radujkovic, Mathilde, Hunault-Berger, Wilfried, Schroyens, Tsila, Zuckerman, Jean Henri, Bourhis, Yves, Chalandon, Adrian, Bloor, Rik, Schots, Liesbeth C, de Wreede, Joana, Drozd-Sokolowska, Kavita, Raj, Nicola, Polverelli, Tomasz, Czerw, Juan Carlos, Hernández-Boluda, Donal, McLornan, and Ibrahim, Yakoub-Agha
Abstract: Allogeneic haematopoietic cell transplant (allo-HCT) provides the only potential route to long-term remission in patients diagnosed with blast phase transformation of myeloproliferative neoplasm (BP-MPN). We report on a large, retrospective EBMT registry-based study of BP-MPN patients undergoing allo-HCT. BP-MPN patients undergoing first allo-HCT between 2005-2019 were included. A total of 663 patients were included. With a median follow-up of 62 months, the estimated 3-year OS was 36% (95% CI, 32-36). Factors associated with lower OS were Karnofsky Performance Status (KPS)90 (HR 1.65, p0.001) and active disease at allo-HCT (HR 1.45, p0.001), whereas patients undergoing allo-HCT more recently associated with a higher OS (HR 0.96, p=0.008). In a selected patients population, the 3-year OS of patients undergoing allo-HCT in complete response (CR) and with a KPS ≥90 was 60%. KPS90 (HR 1.4, p=0.001) and active disease (HR 1.44, p=0.0004) were associated with a lower PFS. Conversely, most recent allo-HCT associated with a higher PFS (HR 0.96, p=0.008). Active disease at allo-HCT (HR 1.34, p=0.03) was associated with a higher cumulative incidence of relapse (RI) and allo-HCT in earlier calendar years (HR 0.96, p=0.02) associated with a lower RI. Lastly, KPS90 (HR 1.91, p0.001), active disease (HR 1.74, p=0.003) and allo-HCT from mismatched related donors were associated with a higher NRM (HR 2.66, p=0.003). In this large series of BP-MPN patients, about one third were alive at 3 years after transplantation. Patients undergoing allo-HCT in the more recent era, with a KPS≥90 and in CR at transplant had a better prognosis. This article is protected by copyright. All rights reserved.
Published: 2022

22. Comparison of scoring systems evaluating suitability for intensive chemotherapy in adults with acute myeloid leukemia-a Grand Ouest Against Leukemia (GOAL) study

Author: Christophe Desprez, Jérémie Riou, Pierre Peterlin, Tony Marchand, Marie-Anne Couturier, Alban Villate, Jean-Baptiste Mear, Patrice Chevalier, Gaelle Guillerm, Emmanuel Gyan, Aline Schmidt-Tanguy, Roland B. Walter, Mathilde Hunault-Berger, Corentin Orvain, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), CHU Pontchaillou [Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), and Fred Hutchinson Cancer Research Center [Seattle] (FHCRC)
Subjects: Adult, Cancer Research, Leukemia, Myeloid, Acute, Oncology, [SDV]Life Sciences [q-bio], Antineoplastic Combined Chemotherapy Protocols, Humans, Hematology, Induction Chemotherapy, Goals, Proportional Hazards Models
Abstract: International audience; Several scoring systems have been developed to assess suitability of individual patients for intensive acute myeloid leukemia (AML) therapy. We sought to compare the performance of these scores in a cohort of 428 consecutive adults with AML who received conventional induction chemotherapy in five academic centers in France. All scoring systems identified a subset of patients with increased 28 and 56-day mortality although the prediction accuracy was overall limited with C-statistics of ranging from 0.61 to 0.71 Overall survival (OS) prediction was more limited and restricted to scoring systems that include AML-related parameters. The outcome of 104 patients (24%) considered unsuitable for intensive chemotherapy based on criteria used in recent randomized trials was similar to that of the other 324 patients (28-day mortality, odds ratio [OR] = 1.88, P = 0.2; 56-day mortality, OR = 1.71, P = 0.21; event-free survival, hazard ratio [HR] = 1.08, P = 0.6; OS, HR = 1.25, P = 0.14) with low discrimination (C-statistic: 0.57, 0.56, 0.50, and 0.52 for 28-day, 56-day mortality, EFS, and OS, respectively). Together, our findings indicate that the accuracy of currently available approaches to identify patients at increased risk of early mortality and shortened survival after intensive AML therapy is relatively limited. Caution regarding the use of available scoring systems should be warranted in clinical decision-making.
Published: 2022

23. Evolution of eligibility criteria for non-transplant randomized controlled trials in adults with acute myeloid leukemia

Author: Corentin Orvain, Megan Othus, Gurleen Johal, Mathilde Hunault-Berger, Frederick R. Appelbaum, and Roland B. Walter
Subjects: Adult, Cancer Research, Leukemia, Myeloid, Acute, Oncology, Humans, Hematology, Comorbidity, Randomized Controlled Trials as Topic
Abstract: Eligibility criteria for clinical trials are intended to select suitable study subjects but can limit trial participation and generalization of results. While reported for other cancers, non-enrollment rates and evolution of eligibility criteria over time have so far not been studied for randomized controlled trials (RCTs) involving adults with acute myeloid leukemia (AML). Among 3698 studies published between 2010 and 2020, including 447 involving prospective clinical trials, we identified 75 phase three RCTs testing non-transplant therapies for adults with AML. Only 31 studies (41%) provided information on non-enrollment; in these studies, the median non-enrollment rate was 23%, primarily attributed to restrictive eligibility criteria. In 95% of trials, eligibility criteria were reported with the total number per trial increasing over time (P 0.001), particularly in industry-funded trials. A total of 27 eligibility criteria were used across trials, mostly concerning comorbidities or performance status, with eight of them becoming more common over time. The concordance with recent ASCO - Friends of Cancer Research eligibility criteria recommendations greatly varied, from 35% to 99%. Together, our analyses suggest that the ability to generalize results from non-transplant RCTs may be increasingly limited because of high non-enrollment rates and increasingly restrictive eligibility criteria.
Published: 2022

24. Blinatumomab + ponatinib for relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

Author: Yosr Hicheri, Célestine Simand, Xavier Thomas, Patrice Chevallier, Maria-Pilar Gallego-Hernanz, Emmanuel Raffoux, Marie-Anne Couturier, Thibaut Leguay, Mathilde Hunault Berger, Céline Berthon, Colombe Saillard, Françoise Huguet, Marie-Christine Béné, and Clémence Loiseau
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Lymphoblastic Leukemia, Philadelphia positive, Antineoplastic Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Refractory, hemic and lymphatic diseases, Internal medicine, Antibodies, Bispecific, Humans, Medicine, Philadelphia Chromosome, Prospective Studies, Retrospective Studies, Philadelphia Chromosome Positive, business.industry, Ponatinib, Imidazoles, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, humanities, Pyridazines, chemistry, 030220 oncology & carcinogenesis, Relapsed refractory, Blinatumomab, business, 030215 immunology, medicine.drug
Abstract: We retrospectively examined the results of a new chemo-free approach combining blinatumomab with ponatinib (blina/pona) in 26 relapsed/refractory Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) patients. All but one achieved complete morphologic remission, and 23 achieved a complete molecular response. With a median follow-up of 34.4 months, the median overall (OS) and event-free (EFS) survivals were 20 and 15.3 months, respectively. After blina/pona, 8 patients underwent an allotransplant (allo), while among the 18 non-transplanted cases, 15 received ponatinib in maintenance. Fifteen relapse/progressions occurred with a significant difference between allo and non allo cases (12.5% vs 82.3%
Published: 2020

25. 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

26. Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples

Author: Philippe Guardiola, Sarah Ghamrawi, Séverine Férec, Mathilde Hunault-Berger, Simon Souchet, Chadi Abbara, Guillaume Drevin, Marie Briet, Jean-Baptiste Robin, Aline Schmidt, Département de Pharmacologie-Toxicologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), Service de Génomique Onco-Hématologique [CHU 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), Service des maladies du sang [CHU Angers], Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Bernardo, Elizabeth
Subjects: Male, 0301 basic medicine, Cancer Research, Time Factors, medicine.medical_treatment, Toxicology, Gastroenterology, 0302 clinical medicine, Drug Stability, AML, Tandem Mass Spectrometry, hemic and lymphatic diseases, Pharmacology (medical), Chromatography, High Pressure Liquid, Randomized Controlled Trials as Topic, Cytarabine, In vitro degradation, Area under the curve, Myeloid leukemia, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, Oncology, Deamination, 030220 oncology & carcinogenesis, Female, Multiple linear regression analysis, Stability, Half-Life, medicine.drug, Adult, Antimetabolites, Antineoplastic, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Clinical pharmacokinetic, Specimen Handling, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cytidine Deaminase, Internal medicine, medicine, Humans, Clinical significance, Pharmacology, Chemotherapy, business.industry, 030104 developmental biology, Clinical Trials, Phase III as Topic, Case-Control Studies, business
Abstract: International audience; Purpose: Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitro cytarabine stability in blood samples obtained from AML patients.Methods: Cytarabine quantification was performed using a fully validated LC/MS/MS method. In vitro cytarabine stability was assessed at room temperature over 24 h in samples coming from 14 AML patients and 7 control patients (CTRL) with no hematological malignancy. In vitro concentrations versus time data were analyzed using a noncompartmental approach.Results: Cytarabine in vitro area under the curve (AUCIVlast) was 22-fold higher in AML samples as compared to CTRL samples (AML mean (standard deviation (SD)), 51,829 (27,004) h ng/mL; CTRL mean (SD), 2356 (1250) h ng/mL, p = 0.00019). This increase was associated with a prolonged in vitro degradation half-life (t1/2IVdeg AML mean (SD), 15 (11.8) h; CTRL mean (SD), 0.36 (0.37) h, p = 0.0033). Multiple linear regression analysis showed that AML diagnosis significantly influenced t1/2IVdeg and AUCIVlas relationship.Conclusion: Cytarabine stability is higher in AML than in CTRL samples. The absence of correlation between t1/2IVdeg and AUCIVlast in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms.
Published: 2020

27. Retrospective Analysis of the Outcomes of Patients with Relapsed/Refractory Acute Myeloid Leukemia Included in a Patient Named Program of Gemtuzumab Ozogamicin

Author: Lambert, Juliette, primary, Peterlin, Pierre, additional, Pautas, Cecile, additional, Raffoux, Emmanuel, additional, Caillot, Denis, additional, Legrand, Ollivier, additional, Joris, Magalie, additional, Berceanu, Anna, additional, Malfuson, Jean Valere, additional, Chantepie, Sylvain, additional, Bernard, Marc, additional, Gastaud, Lauris, additional, Pigneux, Arnaud, additional, Benbrahim, Omar, additional, Bonmati, Caroline, additional, Mathilde, Hunault-Berger, additional, Dombret, Hervé, additional, Rousselot, Philippe, additional, Chevret, Sylvie, additional, and Castaigne, Sylvie, additional
Published: 2021
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28. Impact of Central Nervous System Involvement in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatrics-Inspired Protocol - a Graall Study

Author: Orvain, Corentin, primary, Chantepie, Sylvain, additional, Thomas, Xavier, additional, Escoffre-Barbe, Martine, additional, Huguet, Francoise, additional, Desbrosses, Yohan, additional, Guillerm, Gaelle, additional, Leguay, Thibaut, additional, Barbieux, Sarah, additional, Vey, Norbert, additional, Chevallier, Patrice, additional, Malfuson, Jean Valere, additional, Lepretre, Stephane, additional, Marolleau, Jean Pierre, additional, Zerazhi, Hacene, additional, Carp, Diana, additional, Marçais, Ambroise, additional, Gallego Hernanz, Maria Pilar, additional, Vaida, Iona, additional, Pasquier, Florence, additional, Lheritier, Veronique, additional, Ifrah, Norbert, additional, Dombret, Hervé, additional, Boissel, Nicolas, additional, and Mathilde, Hunault-Berger, additional
Published: 2021
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29. 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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30. 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: Bruno Quesnel, Roland Marion-Gallois, Andrew H. Wei, Muhaimen Siddiqui, Sylvain Chantepie, Brian Hutton, Alessandra Tosolini, Ollivier Legrand, Eytan M. Stein, Arnaud Pigneux, Xavier Thomas, Salem Abi Nehme, Christian Recher, Jixian J. Wang, Mark G. Frattini, Joseph Brandwein, Mathilde Hunault-Berger, Stéphane de Botton, Chris Cameron, Gary Milkovich, and Nicolas Boissel
Subjects: Oncology, Male, Cancer Research, medicine.medical_treatment, Aminopyridines, Hematopoietic stem cell transplantation, Kaplan-Meier Estimate, Multicenter Studies as Topic, Prospective cohort study, RC254-282, Research Articles, Relative survival, Clinical Trials, Phase I as Topic, Triazines, Hazard ratio, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Standard of Care, Middle Aged, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute, Observational Studies as Topic, Treatment Outcome, enasidenib, Female, France, Research Article, IDH2 mutations, Adult, medicine.medical_specialty, Adolescent, overall survival, Enasidenib, acute myeloid leukemia, Young Adult, Clinical Trials, Phase II as Topic, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Propensity Score, Aged, business.industry, Clinical Cancer Research, Confidence interval, Drug Resistance, Neoplasm, Propensity score matching, Mutation, Neoplasm Recurrence, Local, business
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., Overall survival was improved with enasidenib compared with SoC. Enasidenib may be an important advance in treatment for patients with R/R acute myeloid leukemia associated with IDH2 mutations who are ineligible for hematopoietic stem cell transplantation.
Published: 2021

31. WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis

Author: Anne Bouvier, Valérie Ugo, Anaïse Blouet, Alain Zannetti, Mathilde Hunault-Berger, Matgorzata Truchan-Graczyk, Jérémie Riou, Damien Luque Paz, Odile Blanchet, Laurane Cottin, Annaëlle Beucher, Corentin Orvain, Françoise Boyer, Rébecca Jouanneau-Courville, Bénédicte Ribourtout, 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), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (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 des maladies du sang [CHU Angers], Hématologie clinique [CH Cholet], CH Cholet, Hématologie clinique [CH Saumur], Centre Hospitalier de Saumur - CH Saumur, UFR Santé [UNIV Angers], Université d'Angers (UA), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), This work is part of the French clinical and biological network of myeloproliferative neoplasms (FIMBANK) supported by a grant from the Institut National du Cancer (INCa BCB 2013)., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Adult, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Myelofibrosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, urologic and male genital diseases, Myeloproliferative neoplasms, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, hemic and lymphatic diseases, Gene expression, Humans, Medicine, RNA, Messenger, WT1 Proteins, Polycythemia Vera, Molecular Biology, Aged, Aged, 80 and over, Myeloproliferative Disorders, urogenital system, business.industry, Essential thrombocythemia, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Cell Biology, Hematology, Middle Aged, Allografts, medicine.disease, Minimal residual disease, female genital diseases and pregnancy complications, WT1, Transplantation, Leukemia, Myeloid, Acute, 030104 developmental biology, ROC Curve, Primary Myelofibrosis, Cancer research, Molecular Medicine, Stem cell, business, Thrombocythemia, Essential, 030215 immunology
Abstract: International audience; Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexpressed in PMFs and PVs compared to controls. In particular, WT1 transcript levels were higher in PMF than in ET and PV. WT1 transcript levels were significantly increased during myelofibrotic transformation of ET or PV. Using multi-variate linear regression, high WT1 transcript levels in PMF were associated with age over 65, splenomegaly and thrombocytopenia. The ROC curve analysis showed that a level of WT1 transcript > 10 WT1 copies/10 4 ABL1 enabled the diagnosis of PMF with a specificity of 95.8% (PMF vs ET; ROC AUC = 0.91). In myelofibrosis, studying follow-ups of WT1 transcript showed that this marker is of interest after allogeneic SCT. These results demonstrate that WT1 overexpression is a simple marker of myelofibrosis in MPN and could be used during patient follow-up.
Published: 2019

32. Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Author: Norbert Ifrah, Hacene Zerazhi, Pierre-Yves Dumas, Norbert Vey, Isabelle Luquet, Denis Caillot, Marie-Christine Béné, Célestine Simand, Marie-Pierre Ledoux, Véronique Dorvaux, Yosr Hicheri, Anne Banos, Maria Pilar Gallego Hernanz, Chantal Himberlin, Odile Blanchet, Eric Delabesse, Catherine Humbrecht, Pascal Turlure, Arnaud Pigneux, Eric Jourdan, Jacques Delaunay, Didier Bouscary, Emmanuelle Tavernier, Christian Recher, Gaelle Guillerm, Mathilde Hunault-Berger, Romain Guieze, Martin Carre, Anne Bouvier, Jean-Pierre Marolleau, Claude Eric Bulabois, Pascale Cornillet-Lefebvre, Mario Ojeda-Uribe, Marc Bernard, Magda Alexis, Jean-François Hamel, Etienne Daguindau, Pierre Peterlin, Gabrielle Roth Guepin, Emmanuel Gyan, 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), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé du Confluent [Nantes], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], CHU Pontchaillou [Rennes], Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), 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), Centre de Ressources Biologiques [CHU Angers], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Oncology, Adult, Male, Risk, medicine.medical_specialty, NPM1, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Phases of clinical research, Gene mutation, Disease-Free Survival, Cytogenetics, Young Adult, Internal medicine, hemic and lymphatic diseases, CEBPA, Medicine, Cluster Analysis, Humans, Chemotherapy, business.industry, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, General Medicine, Middle Aged, Prognosis, Gemtuzumab, Transplantation, Leukemia, Myeloid, Acute, Karyotyping, Cytogenetic Analysis, Mutation, Female, business
Abstract: International audience; In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (
Published: 2021

33. Data from French named patient program of quizartinib in relapsed/refractory acute myeloid leukemia

Author: Anne Banos, Stefan Wickenhauser, Fabrice Larosa, Filo, R. Redjoul, Pierre-Yves Dumas, Nolwenn Lucas, Jamile Frayfer, Martin Carre, M. Alexis, M. Elassy, Arnaud Pigneux, Emmanuel Raffoux, Pierre Peterlin, Marie-Virginie Larcher, N. Maillard, Christian Recher, J. Michel, J. B. Mear, M. Detrait, V. Morel, Sylvain Chantepie, Mario Ojeda-Uribe, Y. Desbrosses, S. Fodil, Celia Salanoubat, Hervé Dombret, Thomas Cluzeau, C. Mediavilla, Sarah Bertoli, Driss Chaoui, Mathilde Hunault-Berger, and V. Vidal
Subjects: Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Text mining, Internal medicine, medicine, Overall survival, Humans, Benzothiazoles, Quizartinib, Chemotherapy, business.industry, Phenylurea Compounds, Hazard ratio, Myeloid leukemia, Hematology, Leukemia, Myeloid, Acute, chemistry, fms-Like Tyrosine Kinase 3, 030220 oncology & carcinogenesis, Relapsed refractory, business, 030215 immunology, Chemotherapy group
Abstract: Quizartinib improved outcome compared to chemotherapy in the QuANTUM-R study (median overall survival (OS): 6.2 months for quizartinib vs. 4.7 in the chemotherapy group; hazard ratio 0.76, p = 0.02...
Published: 2021

34. In-depth time-dependent analysis of the benefit of allo-HSCT for elderly patients with CR1 AML: a FILO study

Author: Alice Garnier, Gaelle Guillerm, Anne Bouvier, Patrice Ceballos, Marie C. Béné, Yosr Hicheri, Arnaud Pigneux, Christian Recher, Mathilde Hunault-Berger, Sarah Guenounou, Raynier Devillier, Patrice Chevallier, Anne Huynh, Edouard Forcade, Pierre-Yves Dumas, Sylvain Thepot, Didier Blaise, Pierre Peterlin, Norbert Vey, 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Association internationale pour le développement de l’agroenvironnement (AIDA), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Lapeyronie [Montpellier] (CHU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), 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), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d’Oncologie Médicale [IPC, Marseille], and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Allo hsct, Hematopoietic stem cell transplantation, European LeukemiaNet, Recurrence, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Aged, Proportional Hazards Models, business.industry, Hazard ratio, Remission Induction, Complete remission, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, medicine.disease, Leukemia, Leukemia, Myeloid, Acute, Receptors, Complement 3b, business
Abstract: The benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML) aged >60 years remains a matter of debate, notably when performed in first complete remission (CR1). To clarify this issue, the French Innovative Leukemia Organization (FILO) performed a 10-year real-world time-dependent analysis. The study enrolled patients between 60 and 70 years of age with AML in CR1 after intensive chemotherapy with intermediate (IR) or unfavorable (UR) risk according to the European LeukemiaNet (ELN) 2010 classification. The impact of allo-HSCT was analyzed through three models: (1) time-dependent Cox; (2) multistate for dynamic prediction; and (3) super landmark. The study enrolled 369 (73%) IR and 138 (27%) UR patients with AML, 203 of whom received an allo-HSCT. Classical multivariate analysis showed that allo-HSCT significantly improved relapse-free survival (RFS; hazard ratio [HR] [95% confidence interval (CI)], 0.47 [0.35-0.62]; P < .001) and overall survival (OS; HR [95% CI], 0.56 [0.42-0.76]; P < .001), independently of the ELN risk group. With the multistate model, the predicted 5-year probability for IR and UR patients to remain in CR1 without allo-HSCT was 8% and 1%, respectively. Dynamic predictions confirmed that patients without allo-HSCT continue to relapse over time. Finally, the super landmark model showed that allo-HSCT significantly improved RFS (HR [95% CI], 0.47 [0.36-0.62]; P < .001) and OS (HR [95% CI], 0.54 [0.40-0.72]; P < .001). allo-HSCT in CR1 is reported here as significantly improving the outcome of fit older patients with AML. Long-term RFS without allo-HSCT is very low (
Published: 2021

35. Intestinal derivation for digestive complications of graft versus host disease in adult patients: a case series and review of the literature

Author: Sylvain Thepot, Corentin Orvain, Aurelien Giltat, Mathilde Hunault-Berger, Christophe Desprez, Norbert Ifrah, Antoine Hamy, Christopher Nunes Gomes, Aline Schmidt-Tanguy, Benjamin Morvant, and Sylvie François
Subjects: Series (stratigraphy), medicine.medical_specialty, Graft-versus-host disease, Adult patients, business.industry, medicine, Derivation, medicine.disease, business, Surgery
Published: 2021

36. 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

37. 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

38. 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

39. 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

40. Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up

Author: Xavier Troussard, Agnès Olivrie, Gandhi Damaj, Stephanie Noel, Jean-Claude Eisenmann, Olivier Hermine, Jérémie Riou, Sandrine Vaudaux, Patricia Validire-Charpy, Jean Gutnecht, Alain Devidas, Charlotte Petitdidier-Lionnet, Mohamed Touati, Stephanie Haiat, Vincent Levy, Fabienne Huysman, Eric Lippert, Aline Tanguy-Schmidt, Jehan Dupuis, Olivier Lambotte, Clara Mariette, Marouane Boubaya, Edouard Cornet, Pierre Feugier, Mathilde Hunault-Berger, Bertrand Joly, Stéphane Leprêtre, Jérôme Paillassa, Cécile Tomowiak, Kamel Ghomari, Willy Vaillant, Catherine Thieblemont, Mario Ojeda Uribe, Didier Decaudin, Bernard Drenou, Jean-Michel Karsenti, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, Centre Hospitalier Sud Francilien [Corbeil-Essonnes] (CH Sud Francilien), Centre Hospitalier Universitaire [Grenoble] (CHU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier d'Auch (CH Auch), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CH Beauvais, Hôpital Avicenne [AP-HP], 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), 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), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Adult, Male, medicine.medical_specialty, Disease-free survival, medicine.medical_treatment, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Chemotherapy, Hairy cell leukemia, Risk factor, Adverse effect, Cladribine, Aged, Aged, 80 and over, Hairy cell leukaemia, Leukemia, Hairy Cell, Adverse effects, business.industry, Incidence (epidemiology), Hematology, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Leukemia, Treatment Outcome, Risk factors, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business, Pentostatin, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract: In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.
Published: 2020

41. 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

42. 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

43. Donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation

Author: Sylvie François, Aline Schmidt, Mathilde Hunault-Berger, Odile Blanchet, Valérie Ugo, Anne Bouvier, Philippe Guardiola, Corentin Orvain, Annaëlle Beucher, Damien Luque Paz, Alexandre. Guérard, Franck Geneviève, Bénédicte Ribourtout, Bernardo, Elizabeth, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'hématologie (Labo Hémato - 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), Service des maladies du sang [CHU Angers], UFR Santé [UNIV Angers], Université d'Angers (UA), Service de Génomique Onco-Hématologique [CHU Angers], Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), We also thank the 'Ligue contre le cancer' for their support of research on acute myeloid leukemia at Angers Hospital., 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: Adult, Male, Acute promyelocytic leukemia, Donor cell, Transplantation Conditioning, Biopsy, bone marrow transplantation, medicine.medical_treatment, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, acute myeloid leukemia, Donor lymphocyte infusion, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bone Marrow, medicine, Humans, Transplantation, Homologous, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, General Medicine, Middle Aged, medicine.disease, Tissue Donors, 3. Good health, 030220 oncology & carcinogenesis, Immunology, Female, Complication, business, Biomarkers, 030215 immunology
Abstract: International audience; Donor cell leukemia (DCL) is an infrequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its true incidence is difficult to assess, although improvements in chimerism studies contributed to a better diagnosis of DCL. We report two rare cases of donor cell-derived acute promyelocytic leukemia (APL). To our knowledge, only two cases have been described in the literature. Here, we report one male and one female patients with acute myeloid leukemia (AML), who developed an APL in donor cells after HSCT. The latency between HSCT and DCL was 279 and 43 months, respectively. Fluorescent in situ hybridation and chimerism monitoring analysis proved the donor origin of APL. Surprisingly, donor lymphocyte infusion provided a hematological response during 19 months in the female patient. The mechanisms associated with pathogenesis of DCL are unclear and seem to be multifactorial. Increasing worldwide allogeneic hematopoietic stem cell transplantation activity and potentially the age of donor could explain the increasing incidence of DCL in the future. It is highlighted that long-term follow up of recipients will allow to report all cases of DCL, to clarify the genetic landscape and factors which contribute to DCL, to understand the response to DLI.
Published: 2018

44. 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

45. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS

Author: Pierre Fenaux, Iordanis Milionis, Mathilde Hunault Berger, Achilles Anagnostopoulos, Robert Wapenaar, Atanas Radinoff, Maria Antonietta Aloe Spiriti, Valeria Santini, Aristoteles Giagounidis, Argiris Symeonidis, Esther Oliva, Rudolf Schlag, Hari Haralampiev, Liana Gercheva-Kyuchukova, Katharina Götze, Uwe Platzbecker, and Anna Potamianou
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Anemia, Placebo-controlled study, Placebo, Article, Drug Administration Schedule, Hemoglobins, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Clinical endpoint, Humans, Blood Transfusion, Erythropoietin, Aged, Aged, 80 and over, business.industry, Myelodysplastic syndromes, Epoetin alfa, Hematology, Middle Aged, medicine.disease, hematology, oncology, cancer research, ddc, 3. Good health, Discontinuation, Epoetin Alfa, Treatment Outcome, Oncology, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Hematinics, Female, business, 030215 immunology, medicine.drug
Abstract: Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation. A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p
Published: 2018

46. No detection of atypical one-base deletion of CALR exon 9 with fragment analysis: A molecular trap to avoid

Author: Laurane Cottin, Odile Blanchet, Mathilde Hunault-Berger, Maxime Renard, Anne Bouvier, Aurelien Giltat, Damien Luque Paz, Corentin Orvain, Sandrine Lemoine, Valérie Ugo, 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, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Fragment (computer graphics), business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Computational biology, 030204 cardiovascular system & hematology, Trap (computing), 03 medical and health sciences, Exon, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, Molecular Medicine, Medicine, Base (exponentiation), No detection, business, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

47. Caractéristiques cliniques, évolution à long terme et facteurs prédictifs de rechute après arrêt de l’Imatinib au cours de leucémie chronique à éosinophiles associée au réarrangement FIP1L1-PDGFRA: étude rétrospective à propos de 151 patients

Author: Mathilde Hunault-Berger, E. Lengline, F. Lhomme, M. Hamidou, Guillaume Lefèvre, P. Rousselot, Irène Machelart, M. Ebbo, P. Cony Makhoul, Jean-Emmanuel Kahn, Franck E. Nicolini, Aurélien Guffroy, Julien Rohmer, L. Galicier, Olivier Fain, J.S. Bladé, S. Tavitian, M. Groh, and Vincent Cottin
Subjects: Gastroenterology, Internal Medicine
Abstract: Introduction La leucemie chronique a eosinophiles associeeau transcrit FIP1L1-PDGFRA (LCE F/P) est un syndrome hypereosinophilique(SHE) clonal qui presente une grande sensibilite al’Imatinib Mesylate (IM) et dont l’incidence n’est pas connue. Les series publiees a ce jour sont de petite taille, avec un suivi limite et bien que les caracteristiques cliniques ainsi que la possibilite d’arret de l’IM soient connues, aucun facteur predictif de rechute n’a ete mis en evidence. Patients et methodes Etude francaise, multicentrique, retrospective en partenariat avec le groupe des biologistes moleculaires des hemopathies malignes incluant l’ensemble des patients ayant eu une recherche de F/P positive entre 2003 et 2019. Les patients avec une hemopathie aigue ou des donnees cliniques manquantes ont ete exclus. Un modele de regression logistique a ete utilise pour identifier des facteurs de risque de rechute. Resultats Parmi les 197 transcrits F/P positifs, 151 patients ont ete inclus (97 % d’hommes, âge moyen 49 ans). L’incidence de la LCE F/P etait estimee a 0,18 cas par an par million d’habitants. Comme precedemment decrit, les organes les plus frequemment atteints etaient la rate (44 %), la peau (32 %), le poumon (30 %), le coeur (19 %) et le Systeme Nerveux Central (10 %). Par ailleurs, des atteintes vasculaires (thrombose, occlusion arterielle, vascularite), articulaire et renale ont egalement ete decrites. Le pic d’eosinophilie moyen etait de 10,3 (± 6) G/l et les taux de vitamine B12, de tryptase et d’IgE totales etaient eleves dans 74/79 (94 %), 45/57 (79 %) et 12/86 (14 %) des cas tandis qu’une elevation franche de la CRP (i.e. > 40 mg/l) n’etait retrouvee que chez 5 patients. Trente et un (20 %) patients ont ete traites par corticoides sans aucune remission complete tandis que tous les patients traites par IM (n = 148) ont eu une reponse hematologique et moleculaire (n = 84 tests) complete. Parmi les 46 patients ayant arrete l’IM, 20 (47 %) ont presente une rechute. En analyse multivariee, le delai d’introduction du traitement (HR continu : 1,02 [1,00–1,03] ; p = 0,01) et la duree du traitement (HR continu : 0,97 [0,95–0,99] ; p = 0,01) etait des facteurs associes a la rechute. La duree de suivi moyenne etait de 80 (± 56) mois avec une survie globale a 1, 5 et 10 ans de 99 %, 95 % et 84 % respectivement. Conclusion Cette etude avec un large effectif confirme la predominance masculine de cette pathologie ainsi que la frequence des atteintes respiratoire, cardiaque, cutanee et splenique. Apres arret de l’IM une courte duree de traitement prealable et un delais prolonge d’introduction de l’IM etaient associes a la rechute.
Published: 2020

48. Ivosidenib Improves Overall Survival Relative to Standard Therapies in Relapsed or Refractory Mutant IDH1 AML: Results from Matched Comparisons to Historical Controls

Author: Hervé Dombret, John Reitan, Karl-Anton Kreuzer, Evelyn Acuña-Cruz, Mathilde Hunault-Berger, Eyal C. Attar, Thomas Winkler, Pau Montesinos Fernandez, Sylvain Chantepie, Stephanie M. Kapsalis, Christian Recher, Michael Heuser, Sarah C MacDonald, Gary Milkovich, Peter Paschka, Paresh Vyas, Klaus H. Metzeler, Mohamad Mohty, Daniela Weber, Konstanze Döhner, Bruno Quesnel, Michael Dennis, Hua Liu, Stéphane de Botton, Xavier Thomas, Deborah Casso, Hartmut Döhner, Michael Storm, and Arnaud Pigneux
Subjects: Oncology, medicine.medical_specialty, IDH1, business.industry, Immunology, Mutant, Cell Biology, Hematology, Biochemistry, Refractory, Internal medicine, Overall survival, Medicine, business
Abstract: Background: A European Marketing Authorization Application for ivosidenib (IVO) is currently under review for the indication of mutant isocitrate dehydrogenase 1 (mIDH1) R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) in adult patients (pts) who have received ≥ 2 prior regimens, including ≥ 1 standard intensive chemotherapy (IC) regimen, or are not candidates for IC and have received ≥ 1 prior non-intensive regimen. IVO is an oral, potent, targeted inhibitor of mIDH1 and was approved by the FDA for the treatment of mIDH1 R/R AML in 2018, and in newly diagnosed AML in adults ≥ 75 years of age or pts ineligible for IC in 2019, based on the results of the open-label AG120-C-001 (NCT02074839) study. Aims: To evaluate the comparative benefit of IVO within the proposed EU indication, matched pt analyses were conducted using data on mIDH1 R/R AML pts from the AML Study Group (AMLSG) registry (NCT01252485) and a real-world chart review study (RWD) from France, Germany, UK, and Spain. Methods: Individual pt data from Arm 1+ of the AG120-C-001 study (n = 159) was compared to a historical control (HC), combining individual pt data from the AMLSG registry (n = 127) and the RWD (n = 148). A medical review was conducted to identify Arm 1+ IVO pts in the AG120-C-001 study and HC pts who fell within the proposed EU indication. Treatment with IVO was compared with the most recent therapy received by HC pts. HC pts treated with IC as their most recent therapy were excluded, as IVO pts, based on the AG120-C-001 study's eligibility criteria, were not considered candidates for IC. Propensity score-based matching/weighting methods were used to adjust for imbalances in baseline prognostic factors between the 2 cohorts (optimal full matching and inverse probability of treatment weighting [IPTW]). A literature review and data availability led to the inclusion of 6 baseline prognostic factors for estimation of propensity scores (age, history of hematopoietic stem cell transplantation, number of prior regimens for AML, nature of AML, cytogenetic risk, and primary refractory status). Balance between populations was assessed pre- and post-match via comparison of (weighted) standardized differences (SDs) for each covariate. Time-to-event data were summarized via Kaplan-Meier (KM) estimators with 2-sided 95% confidence intervals (CI). Cox regression analysis, using the key prognostic factors as covariates, was applied to estimate hazard ratios (HR) of overall survival (OS), and the corresponding 95% CI was estimated using the sandwich estimator. Complete remission (CR) rates were also compared between IVO pts and RWD non-IC HC pts (AMLSG pts were excluded as the response data did not allow for identification of CRs distinct from other response types). Results: One hundred and nine IVO pts and 60 HC pts fell within the proposed EU indication. The IPTW-matched dataset was selected for analysis, as it more strongly minimized the absolute weighted SDs between cohorts as compared with optimal full matching, with all SDs < 0.05. Median OS was 8.1 months (mo) (95% CI: 5.7, 9.8) with IVO compared with 2.9 mo (95% CI: 1.9, 4.5) in the HC pts. The HR for OS was 0.396 (95% CI: 0.279, 0.562), strongly in favor of IVO (p < 0.0001). There was clear and early separation of the IVO and HC KM curves, reflecting the early and sustained benefit of IVO treatment in this setting (Fig). Six- and 12-mo survival rates in the IVO cohort were 57.7% (95% CI: 48.2, 67.2) and 35.0% (95% CI: 25.7, 44.3), respectively, representing improvements versus 6- and 12-mo survival rates in the HC cohort of 29.1% (95% CI: 17.4, 40.8) and 10.8% (95% CI: 2.7, 18.9), respectively. The IVO cohort also demonstrated higher rates of CR than the HC cohort, with an observed CR rate of 18.3% (95% CI: 11.6, 26.9), compared with 7.0% (95% CI: 1.5, 19.1). Conclusion: IVO monotherapy demonstrated prolonged OS and the potential to increase CR rates vs standard of care therapies in a HC population. Disclosures Paschka: Amgen: Other; AbbVie: Other: Travel, accommodation or expenses, Speakers Bureau; Astellas Pharma: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Travel, accommodations or expenses; Sunesis Pharmaceuticals: Consultancy; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Otsuka: Consultancy; Janssen Oncology: Other; Astex Pharmaceuticals: Consultancy; Agios Pharmaceuticals: Consultancy, Speakers Bureau; BerGenBio ASA: Research Funding. Dombret:Novartis: Consultancy; Cellectis: Consultancy; Sunesis: Consultancy; Abbvie: Consultancy; Immunogen: Consultancy; Celgene: Honoraria; Amgen: Consultancy, Honoraria; Jazz Pharma: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Shire: Honoraria; Otsuka: Consultancy, Honoraria; Menarini: Honoraria; Daiichi Sankyo: Consultancy, Other: travel, accommodation expenses; Incyte: Consultancy, Other: travel, accommodation expenses; Celyad: Consultancy. Montesinos Fernandez:Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vyas:Astellas: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Forty Seven: Research Funding; Pfizer: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; AbbVie: Speakers Bureau. Kreuzer:Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Chugai: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Grifols: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Hexal: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Otsuka: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Ariad: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Baxalta: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Biotest: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau. Heuser:Karyopharm: Research Funding; Janssen: Consultancy; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Abbvie: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; BerGenBio ASA: Research Funding; Bayer: Consultancy, Research Funding; PriME Oncology: Honoraria. Metzeler:Daiichi Sankyo: Honoraria; Otsuka Pharma: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy; Astellas: Honoraria. Quesnel:Abbvie: Other: travel expenses; Daichii Sankyo: Other: travel expenses, Research Funding. Mohty:Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. De Botton:Pierre Fabre: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Servier: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Syros: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Seattle Genetics: Honoraria; Janssen: Consultancy, Honoraria. Döhner:Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Consultancy; Astellas Pharma: Consultancy; Astex Pharmaceuticals: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Sunesis Pharmaceuticals: Research Funding; Janssen: Consultancy, Honoraria; Agios: Consultancy; Novartis: Honoraria, Research Funding; Abbvie: Consultancy. Milkovich:RJM Group LLC: Current Employment. Reitan:RJM Group LLC: Current Employment. MacDonald:IQVIA: Current Employment. Casso:IQVIA: Current Employment. Storm:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Liu:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Kapsalis:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Attar:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Winkler:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Döhner:Agios: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Astex: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Helsinn: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Sunesis: Other, Research Funding.
Published: 2020

49. Different Impact of the Number of Organ Failures and Graft-Versus-Host Disease on the Outcome of Allogeneic Stem Cell Transplantation Recipients Requiring Intensive Care

Author: Philippe Guardiola, Sylvie François, François Beloncle, Sylvain Thepot, Mathilde Hunault-Berger, Achille Kouatchet, Norbert Ifrah, Jean-François Hamel, Jonathan Farhi, Aline Tanguy-Schmidt, Alain Mercat, Mélanie Mercier, Corentin Orvain, Pierre Asfar, 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), Service de Réanimation Médicale et de Médecine Hyperbare [Angers], Centre de Recherche Clinique (CRC Angers), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), 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), Plateforme SNP, Transcriptome & Epigénomique, and Bernardo, Elizabeth
Subjects: Male, Time Factors, medicine.medical_treatment, Graft vs Host Disease, Kaplan-Meier Estimate, law.invention, Patient Admission, 0302 clinical medicine, Risk Factors, law, Odds Ratio, Hospital Mortality, Middle Aged, Intensive care unit, Patient Discharge, 3. Good health, Intensive Care Units, Treatment Outcome, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, Critical Care, Multiple Organ Failure, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, medicine, Humans, Transplantation, Homologous, Renal replacement therapy, Proportional Hazards Models, Retrospective Studies, Mechanical ventilation, Transplantation, Chi-Square Distribution, business.industry, Retrospective cohort study, Odds ratio, medicine.disease, Surgery, Logistic Models, Graft-versus-host disease, Multivariate Analysis, business, Stem Cell Transplantation, 030215 immunology
Abstract: International audience; Background. Admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial , especially when graft-versus-host disease (GVHD) is present. Methods. We performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. Results. Of 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively , whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 μmol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). Conclusions. Early mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.
Published: 2017

50. Premier cas d’abcès cutanés à Staphylococcus aureus sous ibrutinib

Author: R. Chenouard, A. Giltat, Mathilde Hunault-Berger, C. Orvain, S. Hoefsloot, M. Gardembas, A. Schmidt, H. Cormier, and J.B. Robin
Subjects: Gastroenterology, Internal Medicine
Abstract: Introduction L’ibrutinib, inhibiteur irreversible et non specifique de la Bruton tyrosine kinase (BTK), voie du BCR, est utilise dans le traitement de nombreuses hemopathies lymphoides B. L’ibrutinib forme un lien covalent robuste avec la BTK et inhibe les voies de survie et multiplication cellulaires, empechant les cellules lymphomateuses d’adherer aux ganglions lymphatiques, environnement qui leur est favorable. Le traitement entraine une mort cellulaire lors de leur migration dans le sang, environnement qui ne leur est pas favorable. Parmi les effets indesirables connus (cytopenies, troubles digestifs, fibrillation auriculaire, thrombopathies…), on retrouve des complications infectieuses essentiellement bacteriennes, des voies respiratoires et urinaires. Concernant les atteintes cutanees, sont decrit principalement des rashs, un cas de panniculite et un cas d’abces cutanes multiples a Fusarium spp [1]. Observation Nous rapportons le cas d’un homme de 71 ans, diabetique de type 2, traite par ibrutinib depuis juillet 2015 en 2e ligne d’une maladie de Waldenstrom. Un traitement anterieur par 6 cures de rituximab–cyclophosphamide–dexamethasone avait ete initie devant des cytopenies severes (Hb a 4,8 g/L) sans syndrome tumoral associe, avec un echec primaire ayant conduit a l’introduction de l’ibrutinib. En mars 2017, il developpe un premier abces cutane en fosse iliaque gauche necessitant une mise a plat chirurgicale. Aucune documentation microbiologique n’est retrouvee. En juillet 2017, alors que le patient est toujours traite par ibrutinib, et presente une hypogammaglobulinemie a 5,9 g/L (et un pic IgM a 0,6 g/L) et une lymphopenie a 0,7 G/L, sans autre lesion cutanee, survenue d’un nouvel abces spontane paralombaire droit a Staphylococcus aureus meti sensible necessitant une mise a plat chirurgicale de la collection inguinale gauche precedemment operee, et de l’abces paralombaire droit. La recherche du portage de la leucocydine de Panton-Valentine s’avere negative. Devant l’absence d’autre etiologie, outre le diabete favorisant la susceptibilite aux infections, le traitement par ibrutinib est arrete en juillet 2017. L’evolution a ete partiellement favorable sous antibiotherapie, mise en place d’un VAC et soins quotidiens, avec retard de cicatrisation de l’abces inguinal gauche. Depuis son arret, il n’y a pas eu de nouvelle infection, pas de cytopenie, le pic est a 1,2 g/L. Conclusion Nous rapportons, via cette observation, le premier cas d’abces recidivants a S. aureus survenant au cours du traitement par ibrutinib. Le traitement peut etre responsable de complications infectieuses via une diminution de la phagocytose par les macrophages, du chimiotactisme, de l’adhesion et la migration des PNN, la secretion de cytokines pro-inflammatoires et la migration des cellules epitheliales vers le site infectieux.
Published: 2019

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