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1. Frontline Consolidation with Blinatumomab for High-Risk Philadelphia-Negative Acute Lymphoblastic Adult Patients. Early Results from the Graall-2014-QUEST Phase 2

Author: Rathana Kim, Nicolas Boissel, Hervé Dombret, Florence Van Obbergh, Sébastien Maury, Carlos Graux, Yosr Hicheri, Laure Farnault, Yves Chalandon, Thibaut Leguay, Thomas Cluzeau, Cedric Pastoret, Alban Villate, Emmanuelle Clappier, Françoise Huguet, Philippe Rousselot, Martine Escoffre-Barbe, Florence Pasquier, Marie Balsat, Anne Thiebaut-Bertrand, Mathilde Hunault, Eric Delabesse, Patrice Chevallier, Véronique Lhéritier, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Henri Mondor [Créteil], CHU Pontchaillou [Rennes], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier de Versailles André Mignot (CHV), Hôpitaux Universitaires de Genève (HUG), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), and Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Philadelphia negative, medicine.medical_specialty, Adult patients, Consolidation (soil), business.industry, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Biochemistry, Early results, Internal medicine, Medicine, Blinatumomab, business, medicine.drug
Abstract: Introduction: Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) with high-risk genetics and/or measurable residual disease (MRD) are at high-risk of disease recurrence. In the previous GRAALL-2005 study, we identified KMT2A rearrangements (KMT2A-r), IKZF1 intragenic deletion (IKZF1del) and post-induction (TP1, week 6) MRD ≥ 0.01% as independent factors to predict relapse in Ph-negative B-cell precursor (BCP) ALL (Beldjord K, Blood 2014). In the GRAALL-2014 trial, high-risk (HR) patients were thus defined by the presence of at least one of these three factors. Among them, only those with higher MRD levels defined as TP1-MRD ≥ 0.1% and/or week 12 (TP2) MRD ≥ 0.01% were considered at very high risk (VHR) and proposed allogeneic hematopoietic stem cell transplant (alloSCT) in first remission (Dhedin et al., Blood 2015). Since October 2018, all these patients were eligible to be included in the GRAALL-2014-QUEST phase 2 study to receive blinatumomab as part of consolidation and maintenance phases or as a bridge to transplant. Methods: From October 2018 to December 2020, 95 patients with high-risk Ph-negative BCP-ALL without central nervous system involvement at diagnosis and in continuous complete remission after induction and consolidation 1, were prospectively included to start blinatumomab at week 12. One patient was excluded because of T-ALL phenotype (with CD19 aberrant expression). Patients with alloSCT indication and a stem cell source received blinatumomab 28 microg/d administered by continuous intravenous infusion (cIV) until transplant. A minimum of 4 weeks blinatumomab was recommended before proceeding to transplantation. All other patients received 5 cycles of blinatumomab 28 microg/day cIV (for 28 days), during consolidation 2 and 3 and at months 1/3/5 of the maintenance phase respectively. The primary objective was disease-free survival (DFS). Secondary objectives included post-blinatumomab MRD response at TP3 (after consolidation 2 or before alloSCT), overall survival (OS), and safety. Early results are reported here. Results: Median age was 35 years old (range, 18-60). Median white blood cell count (WBC) at diagnosis was 12 G/L (range, 1-449). Oncogenetic analyses allowed classifying ALL as Ph-like (18%), KMT2A-r (17%), DUX4/ERGdel (13%), ZNF384-r (11%), low hypodiploidy/near triploidy (7%), B-other (26%) or unknown (9%). An IKZF1del was found in 37/93 (40%). A TP1-MRD ≥ 0.01% was found in 46/94 patients (49%). Final risk group was HR for 45 patients and VHR for 49 patients. Last pre-blinatumomab MRD was Conclusion. In patients wih high-risk BCP-ALL, blinatumomab added to consolidation is safe and gives promising results. A comparison to similar patients treated in the same GRAALL-2014 study before October 2018 is planned with a longer follow-up. Figure 1 Figure 1. Disclosures Boissel: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; SANOFI: Honoraria; Servier: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; CELGENE: Honoraria; JAZZ Pharma: Honoraria, Research Funding; PFIZER: Consultancy, Honoraria. Huguet: Novartis: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Celgene: Other: Advisor; BMS: Other: Advisor; Amgen: Other: Advisor; Pfizer: Other: Advisor. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. Chalandon: Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Amgen: Other: Advisory Board; Incyte: Speakers Bureau; Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Gilead, Amgen, Jazz, Astra Zenec: Other: Travel EXpenses, Accomodation. Delabesse: Astellas: Consultancy; Novartis: Consultancy. Dombret: Abbvie: Honoraria; Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; NOVARTIS: Research Funding; pfizer: Honoraria, Research Funding; servier: Research Funding; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. OffLabel Disclosure: Blinatumomab in frontline high-risk acute lymphoblastic leukemia
Published: 2021
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2. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients

Author: Martine Escoffre-Barbe, P. Rousselot, Pascale Cony-Makhoul, Stéphane Bouchet, Lambert Busque, Caroline Dartigeas, Franck E. Nicolini, Valérie Coiteux, Françoise Huguet, Laurence Legros, Lydia Roy, Delphine Rea, François Guilhot, Joelle Guilhot, Emilie Cayssials, Francois-Xavier Mahon, Luigina Mollica, Agnès Guerci, Martine Gardembas, Jean-Michel Cayuela, Anne Bergeron, Gabriel Etienne, Viviane Dubruille, Aude Charbonnier, Mathieu Molimard, Centre Hospitalier de Versailles André Mignot (CHV), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hôpital Maisonneuve-Rosemont, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Léon Bérard [Lyon], Institut Bergonié [Bordeaux], UNICANCER, Hôpital Paul Brousse, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Claude Huriez [Lille], CHU Lille, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux Ségalen [Bordeaux 2], CHU de Bordeaux Pellegrin [Bordeaux], Bristol-Myers Squibb, CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.drug_class, Pleural effusion, Dasatinib, Antineoplastic Agents, Gastroenterology, Tyrosine-kinase inhibitor, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, hemic and lymphatic diseases, Clinical endpoint, Humans, Medicine, Cumulative incidence, Prospective Studies, Adverse effect, Protein Kinase Inhibitors, Aged, 030304 developmental biology, Aged, 80 and over, Pharmacology, 0303 health sciences, Dose-Response Relationship, Drug, medicine.diagnostic_test, business.industry, Tyrosine kinases, Hematology, Middle Aged, medicine.disease, Effective dose (pharmacology), 3. Good health, Pleural Effusion, Treatment Outcome, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Chronic leukaemia, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Drug Monitoring, business, medicine.drug
Abstract: International audience; Dasatinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for patients with chronic myeloid leukaemia (CML). Dasatinib 100 mg per day is associated with an increased risk of pleural effusion (PlEff). We randomly evaluated whether therapeutic drug monitoring (TDM) may reduce dasatinib-associated significant adverse events (AEs) by 12 months (primary endpoint). Eligible patients started dasatinib at 100 mg per day followed by dasatinib (C)min assessment. Patients considered overdosed [(C)min ≥ 3 nmol/l) were randomised between a dose-reduction strategy (TDM arm) and standard of care (control arm). Out of 287 evaluable patients, 80 patients were randomised. The primary endpoint was not met due to early haematological AEs occurring before effective dose reduction. However, a major reduction in the cumulative incidence of PlEff was observed in the TDM arm compared to the control arm (4% vs. 15%; 11% vs. 35% and 12% vs. 39% at one, two and three years, respectively (P = 0·0094)). Molecular responses were superimposable in all arms. Dasatinib TDM during treatment initiation was feasible and resulted in a significant reduction of the incidence of PlEff in the long run, without impairing molecular responses. (NCT01916785; https://clinicaltrials.gov).
Published: 2021
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3. Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL

Author: Arnaud Petit, Etienne Lengliné, Stéphane Ducassou, Elizabeth Macintyre, Françoise Huguet, Nicolas Boissel, Virginie Gandemer, Norbert Ifrah, Jean-Michel Cayuela, Guillaume Andrieu, Vahid Asnafi, Aline Schmidt, Nathalie Grardel, Isabelle Arnoux, Carlos Graux, Christophe Bontoux, Marie-Emilie Dourthe, Mathieu Simonin, Hervé Dombret, Ludovic Lhermitte, André Baruchel, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Robert Debré, Hopital Saint-Louis [AP-HP] (AP-HP), CHU UCL Namur, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and 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)
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, IDH1, Adolescent, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease_cause, IDH2, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genotype, Humans, Medicine, PTEN, Diseases of the blood and blood-forming organs, Cumulative incidence, Child, Molecular Biology, RC254-282, 030304 developmental biology, 0303 health sciences, Mutation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hematology, biology, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Middle Aged, Prognosis, Isocitrate Dehydrogenase, 3. Good health, Child, Preschool, 030220 oncology & carcinogenesis, biology.protein, RC633-647.5, business, T-ALL, Rapid Communication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IDH1 and IDH2 mutations (IDH1/2Mut) are recognized as recurrent genetic alterations in acute myeloid leukemia (AML) and associated with both clinical impact and therapeutic opportunity due to the recent development of specific IDH1/2Mut inhibitors. In T-cell acute lymphoblastic leukemia (T-ALL), their incidence and prognostic implications remain poorly reported. Our targeted next-generation sequencing approach allowed comprehensive assessment of genotype across the entire IDH1 and IDH2 locus in 1085 consecutive unselected and newly diagnosed patients with T-ALL and identified 4% of, virtually exclusive (47 of 49 patients), IDH1/2Mut. Mutational patterns of IDH1/2Mut in T-ALL present some specific features compared to AML. Whereas IDH2R140Q mutation was frequent in T-ALL (25 of 51 mutations), the IDH2R172 AML hotspot was absent. IDH2 mutations were associated with older age, an immature phenotype, more frequent RAS gain-of-function mutations and epigenetic regulator loss-of-function alterations (DNMT3A and TET2). IDH2 mutations, contrary to IDH1 mutations, appeared to be an independent prognostic factor in multivariate analysis with the NOTCH1/FBXW7/RAS/PTEN classifier. IDH2Mut were significantly associated with a high cumulative incidence of relapse and very dismal outcome, suggesting that IDH2-mutated T-ALL cases should be identified at diagnosis in order to benefit from therapeutic intensification and/or specific IDH2 inhibitors.
Published: 2021
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4. Influence of major BCR-ABL1 transcript subtype on outcome in patients with chronic myeloid leukemia in chronic phase treated frontline with nilotinib

Author: Nadine Cadoux, Alexandre Janel, Françoise Huguet, Franck E. Nicolini, Marc G. Berger, Pascale Flandrin-Gresta, Sandrine Hayette, Sandrine Saugues, Pascale Cohny-Makhoul, Denis Guyotat, Carole Colin-Gil, Lydia Campos, Alexis Genthon, Jean-Michel Cayuela, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.drug_class, Chromosomal translocation, Chromosome 9, Tyrosine-kinase inhibitor, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Myeloproliferative neoplasm, ComputingMilieux_MISCELLANEOUS, business.industry, Myeloid leukemia, Imatinib, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, 030104 developmental biology, Nilotinib, 030220 oncology & carcinogenesis, Relative risk, business, medicine.drug
Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of BCR-ABL1 transcript as a result of reciprocal translocation between chromosome 9 and 22. The most common transcripts subtypes are e13a2 (b2a2) and e14a2 (b3a2). The prognostic impact of the type of BCR-ABL1 transcript has been the subject of controversies over time. In the imatinib era, several studies have suggested a deeper and faster response in patients expressing e14a2. However, the impact on response after first line therapy with a second-generation tyrosine kinase inhibitor, nilotinib, is unknown. We retrospectively evaluated 118 patients newly diagnosed with chronic phase CML and treated frontline with nilotinib inside or outside clinical trial in five French centers. Only patients expressing e14a2 or e13a2 transcripts alone were analyzed. At baseline, 55.3% expressed e14a2, 44.7% expressed e13a2. The median age was 51 years and median follow-up was 49 months. Relative risks of CML at diagnosis were similar according to the ELTS score (p = .87). Complete hematological response and complete cytogenetic response rates were similar among groups. Patients expressing e14a2 transcripts compared to e13a2 transcripts had deeper and faster molecular responses, when considering MMR (100% vs 84.1%, p = .007) with a median time of 6.7 and 17.1 months or MR4.5 (100% vs 59.9%, p = .005) with a median time of 39.7 and 70.9 months, respectively. A sustained treatment free remission was observed in 10/10 patients with e14a2 versus 1/3 with e13a2 transcript (p = .04). In conclusion, even treated with nilotinib first line, patients with chronic phase CML expressing BCR-ABL1 e13a2 transcript have a lower rate of deep molecular responses.
Published: 2020
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5. Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation

Author: Sylvain Chantepie, Cécile Fourrage, Françoise Huguet, Patrice Chevallier, Elizabeth Macintyre, Hervé Dombret, Nicolas Boissel, Emmanuelle Tavernier, Véronique Lhéritier, Stéphane Leprêtre, Loïc Passini, Vahid Asnafi, Sébastien Maury, Martine Escoffre, Carlos Graux, Ludovic Lhermitte, Emmanuel Raffoux, Patrick Villarese, Norbert Ifrah, Yves Chalandon, Thibaut Leguay, Thorsten Braun, Xavier Thomas, Mathilde Hunault, Rathana Kim, Florian Thonier, Aurore Touzart, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie adulte [Hôpital de 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), 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), Plateforme de Bioinformatique [Paris] (Fondation Imagine), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), 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 [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Groupe de recherche sur la leucémie lymphoblastique aiguë chez l'adulte [Lyon] (CHU HCL - CHLS), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Laboratoire d’Hématologie [CHU Henri-Mondor - APHP], CHU Henri Mondor, CHU Pontchaillou [Rennes], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Genève = University of Geneva (UNIGE), Swiss Group for Clinical Cancer Research [Bern, Switzerland], CHU Dinant-Godinne UCL Namur [Yvoir, Belgique], We thank the Swiss State Secretariat for Education, Research and Innovation (SERI) Switzerland for support. We thank Force Hemato and Association pour la Recherche contre le Cancer (ARC) for support., Bernardo, Elizabeth, 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), 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], University of Geneva [Switzerland], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Neoplasm, Residual, medicine.medical_treatment, Hematopoietic stem cell transplantation, medicine.disease_cause, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, 0302 clinical medicine, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics/pathology/therapy, Receptors, Hematopoietic Stem Cell Transplantation/mortality, ddc:616, Mutation, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, 030220 oncology & carcinogenesis, Tumor/genetics, Residual/genetics/pathology/therapy, Female, Stem cell, Adult, Homologous, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Transplantation, Homologous, Humans, Clinical significance, Interleukin-7 receptor, Chemotherapy, Neoplastic, Transplantation, Receptors, Interleukin-7, business.industry, Minimal residual disease, 030104 developmental biology, Gene Expression Regulation, Interleukin-7/genetics, Neoplasm, business, Biomarkers, Follow-Up Studies
Abstract: International audience; The prognostic value of IL7-receptor pathway (IL7Rp) mutations in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. We performed a comprehensive study of 200 adult patients with TALL included in the GRAALL2003/2005 protocols to address the clinical significance of IL7Rp mutations. Next-generation sequencing of the IL7Rp (IL7R/JAK1/ JAK3/STAT5B) revealed that IL7Rp mutations were frequent in adult TALL (28%) particularly in immature/early T-cell progenitor (ETP)-ALL. They were associated with mutations of NOTCH-pathway, PHF6, and PRC2 components but not with K/NRAS. IL7Rp mutated (IL7Rp mut) TALL were slow-responders, with a high rate of M2/M3 day-8 marrow compared with IL7Rp non-mutated (IL7Rp WT) TALL (p = 0.002) and minimal residual disease positivity at 6-weeks (MRD1) (p = 0.008) but no difference in MRD2 positivity at 12-weeks. Despite this, no adverse prognosis was evidenced when censored for allogeneic hematopoietic stem cell transplantation (HSCT). In time-dependent analysis, HSCT did not benefit IL7Rp mut patients whereas it was of marked benefit to IL7Rp WT cases. IL7Rp-mutations identify a subgroup of slow-responder T-ALLs which benefit from post-induction chemotherapy regimens but not from HSCT. Our data suggest that prior knowledge of the mutation status of IL7Rp may influence HSCT decision and help to guide therapy reduction.
Published: 2020
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6. Outcome of AML patients with IDH2 mutations in real world before the era of IDH2 inhibitors

Author: Laetitia Largeaud, Emilie Bérard, Eric Delabesse, Noémie Gadaud, Naïs Prade, Véronique De Mas, Christian Recher, Pierre Bories, Suzanne Tavitian, Stephanie Dufrechou, Isabelle Luquet, Françoise Huguet, Audrey Sarry, Sarah Bertoli, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Salvage therapy, Enasidenib, IDH2, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, In patient, Complete response, Aged, Retrospective Studies, business.industry, Myeloid leukemia, Hematology, Middle Aged, Prognosis, Isocitrate Dehydrogenase, 3. Good health, Clinical trial, Survival Rate, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Female, Neoplasm Recurrence, Local, business, 030215 immunology, Follow-Up Studies
Abstract: Describing the prognosis of sub-groups of acute myeloid leukemia (AML) patients treated in real world with current therapies is becoming increasingly relevant to estimate the benefit that new targeted drugs will bring in the field. This is particularly the case when novel drugs are registered on the basis of non-randomized studies. IDH2 inhibitors have recently emerged as promising drugs in patients with IDH2R140 or IDH2R172 mutations. Enasidenib, a first-in-class IDH2 inhibitor, has been approved following promising results of a phase 1-2 clinical trial in relapsed or refractory AML patients with IDH2 mutations. In this study, we described the characteristics, treatments and outcome of 75 IDH2 mutated patients both at diagnosis and relapse or refractory disease. Among the 33 relapsed/refractory AML patients with either IDH2R140 or IDH2R172, 28 (84.8%) patients received salvage therapy and 14 achieved a complete response (50%). Median duration of response was 15.2 months. Median, 1-y, 3-y and 5-y OS were 15.1 months (IQR, 4.6-37.7), 53.1% (95% CI, 33.2-69.5), 29.2% (95% CI, 12.6-48.1) and 24.4% (95% CI, 9.3-43.1), respectively. In responding patients, median OS was 37.7 months and 1-y, 3-y and 5-y OS was 85.7%, 57.1% and 47.6%, respectively. In non-responding patients, median OS was 5.0 months (IQR, 4.5-8.6) and 1-y and 3-y OS was 17.9% and 0%, respectively. Thus, a substantial number of R/R AML patients with IDH2 mutations can be salvaged by current treatments and benefit from prolonged survival. It is expected that novel targeted agents such as enasidenib will further improve efficacy and safety in the next future.
Published: 2019
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7. DNMT3A mutation is associated with increased age and adverse outcome in adult T-acute lymphoblastic leukemia

Author: Hervé Dombret, Yosr Hicheri, Stéphane Leprêtre, Thibaut Leguay, Ludovic Lhermitte, Jonathan Bond, Norbert Ifrah, Karin Bilger, Véronique Lhéritier, Françoise Huguet, Gaelle Guillerm, Elizabeth Macintyre, Mathilde Hunault, Yves Chalandon, Mario Bargetzi, Aurore Touzart, Guillaume Hypolite, Vahid Asnafi, Nicolas Boissel, Carlos Graux, Univ Angers, Okina, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU UCL Namur, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Coordination du Groupe GRAALL [CH Lyon-Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Genève = University of Geneva (UNIGE), Swiss Group for Clinical Cancer Research [Bern, Switzerland], Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), 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), CHU Toulouse [Toulouse], University of Geneva [Switzerland], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
Subjects: Oncology, medicine.medical_specialty, Adverse outcomes, [SDV]Life Sciences [q-bio], Cell, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Text mining, Internal medicine, Genotype, medicine, Adult Acute, ddc:616, Cytogenetics and Molecular Genetics, business.industry, Hematology, Acute Lymphoblastic Leukemia, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Adult Acute Lymphoblastic Leukemia, Institutional repository, medicine.anatomical_structure, chemistry, Adult T-Cell Acute Lymphoblastic Leukemia, Mutation (genetic algorithm), embryonic structures, Lymphoblastic Leukemia, DNMT3A, business, DNA, 030215 immunology
Abstract: The prognostic implications of DNMT3A genotype in T-cell acute lymphoblastic leukemia are incompletely understood. We performed comprehensive genetic and clinico-biological analyses of T-cell acute lymphoblastic leukemia patients with DNMT3A mutations treated during the GRAALL-2003 and -2005 studies. Eighteen of 198 cases (9.1%) had DNMT3A alterations. Two patients also had DNMT3A mutations in non-leukemic cell DNA, providing the first potential evidence of age-related clonal hematopoiesis in T-cell acute lymphoblastic leukemia. DNMT3A mutation was associated with older age (median 43.9 years vs. 29.4 years, P
Published: 2019
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8. The odyssee study: prevention of dysbiosis complications with autologous fecal microbiota transfer (fmt) in acute myeloid leukemia (aml) patients undergoing intensive treatment: results of a prospective multicenter trial

Author: Joël Doré, Mauricette Michallet, Simona Lapusan, Florent Malard, Patrice Chevallier, Sophie Ducastelle-Lepretre, Suzanne Tavitian, Colombe Saillard, Stephanie Nguyen-Quoc, Xavier Thomas, Emilie Plantamura, Pierre Peterlin, Clément Rocher, Lilia Boucinha, Anne Vekhoff, Françoise Huguet, Ollivier Legrand, Evelyne D'Incan, Anne-Sophie Michallet, Christian Recher, Etienne Paubelle, Cyrielle Gasc, Jerome Rey, Lila Gilis, Mohamad Mohty, Françoise Isnard, Marie Virginie Larcher, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Service d'hématologie, Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MaaT Pharma [Lyon], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MaaT Pharma, and American Society of Hematology (ASH). USA.
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Population, Biochemistry, law.invention, 03 medical and health sciences, Randomized controlled trial, law, Internal medicine, Multicenter trial, medicine, Clinical endpoint, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, Induction chemotherapy, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, 030104 developmental biology, business, Dysbiosis
Abstract: Introduction. AML standard intensive induction chemotherapy ("3+7" or equivalent) combined with wide spectrum antibiotics can dramatically alter the composition of the gut microbiota, leading to dysbiosis which is characterized by loss of microbial diversity. Such dysbiosis status can promote a pathological condition involving uncontrolled local immune responses, systemic inflammation and increased incidence of adverse events. The development of FMT-based drugs to restore microbial communities could offer novel therapeutic possibilities to reduce such adverse events and potentially improve outcomes in AML. We therefore conducted this single arm prospective phase I/II multicenter trial (NCT02928523) to evaluate the use of a FMT-based drug in association with AML induction treatment to restore the gut microbiota diversity. Patients and methods. A total of 62 consecutive patients aged between 24 and 69 years old with a diagnosis of de novo AML were screened in 7 French sites. At time of admission and AML diagnosis (Step 1=S1), patients' faeces were collected, rigorously screened, prepared following a standardized process, and stored at -80°C until later administration. The drug was administered as an enema after hematopoietic recovery (S2) and before consolidation chemotherapy (Conso). The primary endpoint was the recovery of at least 70% of microbiota diversity (based on the Simpson index) after drug administration and the reduction of multidrug resistant bacteria carriage. Blood and feces samples were collected at S1, S2, and around 10 days post-FMT before Conso (S3). Microbiome diversity restoration was assessed by metagenomics analysis through Illumina HiSeq shotgun sequencing. Antibiotic resistance gene carriage (ARGC, also known as resistome) was evaluated through mapping of readouts on the MEGARES database. Secondary objectives included safety and analysis of host response with assessment of blood and fecal markers by ELISA and Luminex. Results. Overall, 25 patients were actually treated with FMT, and 20 were included in the per-protocol population. Induction Chemotherapy (IC) induced a dramatic shift in microbial communities, with a significant 42.3% decrease of mean α-diversity Simpson index between S1 and S2 at species level (0.85 to 0.50; p No serious adverse events (SAE) were observed within 30 days after FMT and all post FMT SAEs were not related to the FMT procedure. Moreover, FMT did not induce any local or systemic inflammatory reaction as measured by fecal and blood markers (fecal neopterin and IgA; plasmatic CRP, IL-6 and sCD14). Interestingly, restoration of the microbiome diversity was associated with a significant reduction of CRP and fecal neopterin levels, suggesting a potential anti-inflammatory impact of FMT. Overall, FMT was well tolerated and had an excellent safety profile. The one-year overall survival estimate in the whole cohort was 84% (4 deaths among 25, none of which were related to FMT: 2 multiple organ failures, 1 heart attack and 1 grade IV resistant GVHD). The median time to death from the second FMT was 182.5 days (113-225 days). Conclusions. This is the first prospective trial testing the safety and efficacy of FMT in AML patients receiving intensive induction chemotherapy. The trial achieved its primary endpoint and established the capacity of FMT to restore a diverse microbiome with high levels of similarity to baseline, as well as reducing ARGC and intestinal inflammation. A controlled randomized trial with repeated FMT administrations is currently planned to further evaluate the impact of FMT on clinical outcomes and long-term survival. (This trial was funded by MaaT Pharma whose product was tested in this protocol). Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria. Doré:MaaT Pharma: Consultancy, Honoraria.
Published: 2018
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9. Ponatinib evaluation and safety in real-life chronic myelogenous leukemia patients failing more than two tyrosine kinase inhibitors: the PEARL observational study

Author: Maël Heiblig, Stephane Morisset, Franck E. Nicolini, Lucila Sackmann-Sala, Viviane Dubruille, Philippe Rousselot, Lydia Roy, Shanti Ame, Delphine Rea, Gabriel Etienne, Marie-Lorraine Chretien, Françoise Huguet, Aude Charbonnier, Emilie Cayssials, Agnès Guerci-Bresler, Valérie Coiteux, Mohamad Sobh, Eric Hermet, Martine Escoffre-Barbe, Centre Léon Bérard [Lyon], Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Claude Huriez [Lille], CHU Lille, CHU Pontchaillou [Rennes], Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Compassionate Use Trials, Male, Oncology, Cancer Research, Salvage therapy, Kaplan-Meier Estimate, Tyrosine-kinase inhibitor, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Cumulative incidence, Treatment Failure, Aged, 80 and over, Ponatinib, Imidazoles, Hematology, Middle Aged, Intention to Treat Analysis, 3. Good health, Pyridazines, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genes, abl, Young Adult, 03 medical and health sciences, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, Pragmatic Clinical Trials as Topic, Genetics, Humans, Adverse effect, Protein Kinase Inhibitors, Molecular Biology, Survival analysis, Aged, Salvage Therapy, business.industry, Patient Selection, Cell Biology, medicine.disease, Survival Analysis, Clinical trial, chemistry, Drug Resistance, Neoplasm, business, 030215 immunology, Chronic myelogenous leukemia
Abstract: IF 2.436 (2017); International audience; Ponatinib represents a remarkable progress in the treatment of heavily pretreated chronic myelogenous leukemia (CML) and de novo Philadelphia chromosome-positive ALL patients despite significant toxicity in clinical trials. To date, "real-life" data remain few and the use of ponatinib in this setting and its consequences remain mostly unknown. We report, within a national observational study, the use of ponatinib in unselected CML patients who had previously failed ≥2 lines of tyrosine kinase inhibitor (TKI) therapy (or one line if an Abelson (ABL)T315I mutation was identified), in real-life conditions (2013-2014) in a compassionate program. Our analysis has been focused on 48 chronic phase CML patients recorded. With a median follow-up of 26.5 months since ponatinib initiation, the overall survival (OS) rates (80.5% at 3 years) and cumulative incidence of major molecular response (81.8% at 18 months) were similar to those of the phase II study, with no influence of BCR-ABL mutations nor the reason of ponatinib prescription. A specific subanalysis of the preexisting cardiovascular risk factors and events occurring on ponatinib is described. These events occurred after a median time on ponatinib of 5.8 months (excluding hypertension) and were observed in 29/48 patients (47%), even in those already on anti-aggregants/coagulants. The majority were not severe and resolved, but two cases were fatal. Other hematological or nonhematological nonvascular adverse events were similar to those previously described in trials. This observational study reports similar rates of survival, molecular responses, and a slight increase in the cardiovascular toxicity of ponatinib in real-life conditions, prompting improved control of cardiovascular risk factors and selection of patients.
Published: 2018
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10. Monitoring of asparagine depletion and anti-L-asparaginase antibodies in adult acute lymphoblastic leukemia treated in the pediatric-inspired GRAALL-2005 trial

Author: Mathilde Hunault-Berger, Xavier Thomas, Véronique Lhéritier, Norbert Ifrah, Christine Vianey-Saban, Hervé Dombret, Cécile Acquaviva-Bourdain, Thibaut Leguay, Jérôme Paillassa, Marie Audrain, Cécile Pagan, Nicolas Boissel, Françoise Huguet, Innate immunity and Immunotherapy ( CRCINA - Département INCIT - Equipe 7 ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service des maladies du sang [Angers], CHU Angers, Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d’Hématologie Clinique [CHU de Lyon], CHU de Lyon, Service d’hématologie Clinique [CHU Toulouse], CHU Toulouse [Toulouse], Laboratoire d'Immunologie [CHU Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Coordination du Groupe GRAALL [CH Lyon-Sud], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] ( Centre de Biologie et Pathologie Est ), Hospices Civils de Lyon ( HCL ) -Groupement Hospitalier Est, Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] ( ORS PACA ), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Bernardo, Elizabeth
Subjects: Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology, lcsh:RC254-282, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, L asparaginase, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Isoantibodies, Correspondence, Medicine, Asparaginase, Humans, Asparagine, Child, ComputingMilieux_MISCELLANEOUS, biology, business.industry, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Clinical trial, Oncology, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Adult Acute Lymphoblastic Leukemia, biology.protein, Female, Antibody, business, 030215 immunology
Abstract: International audience; no abstract
Published: 2018
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11. Natural killer-cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study

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

Author: M C Béné, Françoise Huguet, Chantal Himberlin, Norbert Ifrah, Marina Lafage-Pochitaloff, Marc Renaud, Patrice Chevallier, Pascal Turlure, K. Beldjord, Françoise Isnard, B. Lioure, Xavier Thomas, Véronique Lhéritier, Mathilde Hunault, E. Tavernier, Vahid Asnafi, Hervé Dombret, A. Charbonnier, A. Desjonquères, Jacques-Olivier Bay, Stéphane Leprêtre, Thibaut Leguay, J. N. Bastie, Marc Bernard, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hématologie [Institut de Cancérologie de la Loire], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie Clinique [CHU Reims], Hôpital universitaire Robert Debré [Reims], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Male, Survival, analysis, medicine.medical_treatment, Hematopoietic stem cell transplantation, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Philadelphia Chromosome, Young adult, Child, Hematology, Leukemia, Remission Induction, Hematopoietic Stem Cell Transplantation, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Treatment Outcome, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Imatinib Mesylate, Female, Original Article, France, Rituximab, Adult, medicine.medical_specialty, Adolescent, Patients, [SDV.CAN]Life Sciences [q-bio]/Cancer, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Disease-Free Survival, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Transplantation, Homologous, Molecular Biology, therapy, business.industry, medicine.disease, Transplantation, Clinical trial, Immunology, Multivariate Analysis, Adult Acute Lymphoblastic Leukemia, business, Laboratories, 030215 immunology
Abstract: The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph− ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph− ALL younger adults (18–63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14–24%) and 13.3% (8–18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21–38%) and 25% (17–33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (PP=0.004, respectively) and longer OS (P=0.004 and P
Published: 2016
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13. CML patients show sperm alterations at diagnosis that are not improved with imatinib treatment

Author: Franck-Emmanuel Nicolini, Volcy Soula, Marie-Pierre Fort, Vincent Alcazer, Agnès Guerci-Bresler, Maël Heiblig, Myriam Daudin, Pascale Cony-Makhoul, Stephane Morisset, Françoise Huguet, Sandrine Giscard d'Estaing, Gabriel Etienne, Mohamad Sobh, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Du site actif au matériau catalytique (E3) (SAMCat ), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut de Chimie du CNRS (INC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut de Chimie du CNRS (INC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Du site actif au matériau catalytique (E3), Institut de Chimie des Milieux et Matériaux de Poitiers ( IC2MP ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ) -Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service 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), and Centre Hospitalier Lyon-Sud (Centre Hospitalier Lyon-Sud)
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Patients, diagnosis, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Imatinib treatment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Myelogenous, Young Adult, 0302 clinical medicine, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Young adult, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, 030219 obstetrics & reproductive medicine, business.industry, Reproduction, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, Sperm, Spermatozoa, 3. Good health, Leukemia, 030220 oncology & carcinogenesis, Imatinib Mesylate, France, business
Abstract: International audience
Published: 2016
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14. Recommandations 2015 du France Intergroupe des Leucémies Myéloïdes Chroniques pour la gestion du risque d'événements cardiovasculaires sous nilotinib au cours de la leucémie myéloïde chronique

Author: Martine Escoffre-Barbe, Shanti Ame, Simona Lapusan, Eric Hermet, Martine Gardembas, Philippe Rousselot, Pascale Cony-Makhoul, Francois-Xavier Mahon, Aude Charbonnier, Valérie Coiteux, Franck E. Nicolini, Michel Tulliez, Philippe Quittet, Gabriel Etienne, Emmanuel Messas, Delphine Rea, Françoise Huguet, Laurence Legros, Hyacinthe Johnson-Ansah, Agnès Guerci-Bresler, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, CHU Pontchaillou [Rennes], Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’Hématologie Clinique Adulte et de Thérapie Cellulaire, CHU Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Le Collège d'études mondiales/FMSH, Fondation Maison des sciences de l'homme (FMSH), Institut Bergonié [Bordeaux], UNICANCER, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Eloi, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut Bergonié - CRLCC Bordeaux, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Risk, Cancer Research, medicine.medical_specialty, Patients, Survival, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, Tyrosine-kinase inhibitor, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Radiology, Nuclear Medicine and imaging, Adverse effect, Leukemia, business.industry, Myeloid leukemia, Imatinib, Hematology, General Medicine, medicine.disease, mortality, 3. Good health, Nilotinib, Tolerability, 030220 oncology & carcinogenesis, France, business, Tyrosine kinase, medicine.drug
Abstract: International audience; Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein represent an outstanding progress in chronic myeloid leukemia and long-term progression-free survival has become a reality for a majority of patients. However, tyrosine kinase inhibitors may at best chronicize rather than cure the disease thus current recommendation is to pursue treatment indefinitely. As a consequence, high quality treatment and care must integrate optimal disease control and treatment tolerability. Tyrosine kinase inhibitors have an overall favorable safety profile in clinical practice since most adverse events are mild to moderate in intensity. However, recent evidence has emerged that new generation tyrosine kinase inhibitors may sometimes damage vital organs and if not adequately managed, morbidity and mortality may increase. The 2nd generation tyrosine kinase inhibitor nilotinib is licensed for the treatment of chronic myeloid leukemia with resistance or intolerance to imatinib and newly diagnosed chronic phase-chronic myeloid leukemia. Nilotinib represents an important therapeutic option but it is associated with an increased risk of cardiovascular events. The purpose of this article by the France Intergroupe des Leucemies Myeloides Chroniques is to provide an overview of nilotinib efficacy and cardiovascular safety profile and to propose practical recommendations with the goal to minimize the risk and severity of cardiovascular events in nilotinib-treated patients
Published: 2016
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15. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study

Author: Patrice Chevallier, Carlos Graux, Vahid Asnafi, Anne Moreau, Thomas Vermeulin, Jacques Benichou, Gilles Salles, Stephanie Seris, Josette Brière, Norbert Ifrah, Aline Tanguy-Schmidt, Stéphane Leprêtre, Elizabeth Macintyre, Marie-Christine Béné, Jean-Michel Picquenot, Aurore Touzart, Serge Bologna, Reda Bouabdallah, Valérie Tallon-Simon, Françoise Huguet, Emmanuel Raffoux, Thierry Lamy, Hervé Dombret, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Charles Nicolle [Tunis], Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), HEMATOLOGIE, CRLCC Henri Becquerel, Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie clinique, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Purpan ( CHU Purpan ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Cliniques Universitaires UCL de Mont-Godinne, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), The study was supported by a grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique of France [PHRC 2003 No. 13-2]). The Macintyre laboratory was supported by the Fondation de France, the Association de Recherche sur le Cancer, Cent pour Sang la Vie, and the Société Française des Cancers de l’Enfant. CHUGAI PHARMA France provided technical and financialsupport., Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de biostatistiques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Université Toulouse III - Paul Sabatier ( UPS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Bernardo, Elizabeth
Subjects: Male, Cancer Research, F-Box-WD Repeat-Containing Protein 7, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Phases of clinical research, Cell Cycle Proteins, Hematopoietic stem cell transplantation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Central Nervous System Diseases, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Young adult, Receptor, Notch1, Prospective cohort study, Hematopoietic Stem Cell Transplantation, Induction Chemotherapy, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, Ubiquitin-Protein Ligases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, medicine, Humans, Survival rate, [ SDV ] Life Sciences [q-bio], L-Lactate Dehydrogenase, business.industry, F-Box Proteins, Lymphoblastic lymphoma, PTEN Phosphohydrolase, Induction chemotherapy, medicine.disease, Surgery, Consolidation Chemotherapy, ras Proteins, business, 030215 immunology
Abstract: Purpose This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). Patients and Methods This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. Results The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. Conclusion In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.
Published: 2016
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16. Prevention of Venous Thrombotic Events in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatric-Inspired Protocol - a Graall Study

Author: Emmanuelle Tavernier, Denis Caillot, Yves Chalandon, Sylvain Chantepie, Françoise Huguet, Thomas Pabst, Norbert Ifrah, Corentin Orvain, Nicolas Boissel, Hervé Dombret, Patrice Chevallier, Marie Balsat, Mathilde Hunault-Berger, Véronique Lhéritier, Jamile Frayfer, Victoria Cacheux, Noémie de Gunzburg, Jean-Pierre Marolleau, Caroline Bonmati, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'hématologie, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Amiens-Picardie, Inselspital Bern, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier de Meaux, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), PRES Université Nantes Angers Le Mans (UNAM), and DESSAIVRE, Louise
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, business.industry, Cell Biology, Hematology, Odds ratio, medicine.disease, Thrombosis, Surgery, Discontinuation, Pulmonary embolism, Transplantation, [SDV] Life Sciences [q-bio], Venous thrombosis, Platelet transfusion, 030220 oncology & carcinogenesis, Fresh frozen plasma, business
Abstract: Background: Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP) and subsequent antithrombine (AT) deficiency. Previous reports showed that patients with venous thrombotic events (VTE) have a lower event-free survival that may be due to early discontinuation of L-ASP. It has been suggested that AT replacement could decrease the rate of thrombosis and prevent L-ASP discontinuation. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Methods: All patients received a 5-drug induction therapy with 8 native E. Coli-ASP intravenous injections (6,000 UI/m2/injection). Patients in complete remission (CR) received two consolidation courses each containing two L-ASP intravenous injections (10000 UI/m2/injection). All patients in persistent CR for whom allogeneic stem cell transplantation was not indicated in first CR received a late intensification with the same drugs as in the induction course, followed by the repetition of one consolidation course. Platelet transfusion support was recommended for platelets below 20 x 109/L, fresh frozen plasma (FFP) or fibrinogen concentrates were recommended if fibrinogen levels fell below 0.5 g/L, and AT concentrate substitution therapy was recommended in order to maintain AT levels above 60%. Prophylactic heparin was recommended during induction and late intensification. All cases of VTE were identified prospectively by clinical signs and confirmed by radiological imaging based on institutional guidelines. Results: Between 2006 and 2014, 787 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 14.4% (113 VTEs in 110 patients). VTEs included 72 (64%) deep vein thromboses (DVT), with one third in the lower limb and two thirds in the upper limb, 32 (28%) cerebral venous thrombosis (CVT), and 13 (12%) pulmonary embolism (PE). No disease characteristic was associated with a higher risk of thrombosis. Patients with DVT and/or PE were older (median age of 40 versus 38 for those with CVT versus 35 for those without VTE, p=0.04), had a higher BMI (median BMI of 26 versus 23 for those with CVT and 24 for those without VTE, p=0.01), and had a higher platelet count at diagnosis (median platelet count of 100 G/l versus 84 G/l for those with CVT versus 68 G/l for those without VTE, p=0.06) whereas patients with CVT had higher hemoglobin levels (median hemoglobin level of 11.7 g/dl versus 10.1 g/dl for those with DVT/PE versus 10.2 g/dl for those without VTE, p=0.03). Sixty-seven percent of VTEs occurred during induction therapy. Other VTEs occurred as follows: 17 (15%) during consolidation phase 1 (688 patients), 4 (4%) during consolidation phase 2 (537 patients), 9 (8%) during late intensification (356 patients), and 7 (6%) in 335 during consolidation phase 3 (335 patients). The type of thrombosis was different according to treatment phase as most CVT occurred during induction therapy (29 versus 3 CVTs during subsequent phases of treatment, p=0.003). During induction therapy, patients with VTE were more likely to have received heparin prophylaxis (82% versus 60% for those without VTE, odds ratio (OR) 1.8, p=0.06) and fibrinogen prophylaxis (14% versus 8% for those without VTE, OR 2, p=0.05) whereas they received less AT prophylaxis (82% versus 88% for those without VTE, OR 0.5, p=0.05). Patients with VTE received less L-ASP infusions during induction therapy (median number of 7 versus 8 injections for those without VTE, p Conclusion: In ALL patients receiving L-ASP therapy, appropriate AT prophylaxis was associated with less VTE and should be used extensively. Maintaining higher AT levels in patients at increased risk for VTE should be evaluated. L-ASP can be reintroduced in patients who experienced VTE during induction as none had thrombotic recurrence. Fibrinogen concentrates may increase the risk of thrombosis and should be restricted to patients with hemorrhage. Disclosures Dombret: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.
Published: 2016
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17. Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic Malignancies

Author: Florence Abravanel, Suzanne Tavitian, Stanislas Faguer, Christian Recher, Clément Gaudin, Odile Beyne-Rauzy, Loic Ysebaert, Laurent Alric, Jean-Marie Peron, Françoise Huguet, Anne Huynh, Lucie Oberic, Nassim Kamar, Murielle Roussel, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Pagès, Nathalie
Subjects: Cirrhosis, Epidemiology, viruses, [SDV]Life Sciences [q-bio], lcsh:Medicine, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Hepatitis E virus, Cytotoxic T cell, Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic Malignancies, Hepatitis, Chronic, 0303 health sciences, Hematology, hematology, Dispatch, food and beverages, virus diseases, Hepatitis E, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Hematologic Neoplasms, Cohort, 030211 gastroenterology & hepatology, chronic hepatitis, Microbiology (medical), medicine.medical_specialty, ribavirin, Malignancy, Antiviral Agents, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Internal medicine, medicine, Humans, lcsh:RC109-216, 030304 developmental biology, business.industry, Ribavirin, cirrhosis, lcsh:R, fungi, medicine.disease, digestive system diseases, chemistry, Immunology, business, malignancy
Abstract: International audience; Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies.
Published: 2015
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18. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

Author: Raouf Ben Abdelali, Véronique Lhéritier, Jean-Yves Cahn, Françoise Huguet, Norbert Ifrah, Agnès Buzyn, Noémie de Gunzburg, Elizabeth Macintyre, Vahid Asnafi, Dominique Payet-Bornet, Sébastien Maury, Jonathan Bond, Thibaud Leguay, Amélie Trinquand, Bertrand Nadel, André Delannoy, Kheira Beldjord, Hervé Dombret, Xavier Thomas, Jérôme Lambert, Ludovic Lhermitte, Hossein Mossafa, Etienne Lengliné, Yves Chalandon, Caroline Bonmati, Aline Tanguy-Schmidt, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Cytogénétique - Pasteur-Cerba, Laboratoire Pasteur-Cerba, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Hôpital de Jolimont, Haine-Saint-Paul and Cliniques Universitaires St Luc, Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service 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), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Toulouse III - Paul Sabatier (UT3), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche en Cancérologie de Lyon (CRCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Ras Proteins/genetics, Oncology, Pathology, MESH : F-Box Proteins, DNA Mutational Analysis, Cell Cycle Proteins, MESH : Gene Deletion, MESH: Receptor, Notch1, 0302 clinical medicine, MESH : Cell Cycle Proteins, Receptor, Notch1, MESH: DNA Mutational Analysis, Young adult, ddc:616, 0303 health sciences, Hazard ratio, PTEN Phosphohydrolase/genetics, hemic and immune systems, 3. Good health, MESH : Phenotype, MESH: Young Adult, 030220 oncology & carcinogenesis, Predictive value of tests, Cohort, F-Box Proteins/genetics, MESH : Proto-Oncogene Proteins, MESH: Membrane Proteins, MESH: ras Proteins, medicine.medical_specialty, MESH : Young Adult, MESH : DNA Mutational Analysis, MESH: Phenotype, MESH: PTEN Phosphohydrolase, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, MESH: Cell Cycle Proteins, Humans, PTEN, Ubiquitin-Protein Ligases/genetics, MESH : Predictive Value of Tests, MESH: Kaplan-Meier Estimate, Cell Cycle Proteins/genetics, Receptor, Notch1/genetics, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Humans, Proportional hazards model, F-Box Proteins, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, MESH: Ubiquitin-Protein Ligases, MESH : Membrane Proteins, MESH: Disease-Free Survival, Mutation, ras Proteins, Adult Acute Lymphoblastic Leukemia, MESH : Genetic Predisposition to Disease, MESH : Ubiquitin-Protein Ligases, MESH : GTP Phosphohydrolases, MESH: Female, Gene Deletion, Cancer Research, F-Box-WD Repeat-Containing Protein 7, Time Factors, MESH : Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Kaplan-Meier Estimate, MESH : PTEN Phosphohydrolase, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, GTP Phosphohydrolases, MESH: Proportional Hazards Models, MESH: Risk Factors, Risk Factors, hemic and lymphatic diseases, MESH : Female, biology, MESH : Receptor, Notch1, MESH: Genetic Predisposition to Disease, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, MESH: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Phenotype, MESH : Disease-Free Survival, Female, MESH : Mutation, MESH : Time Factors, Adult, MESH: Mutation, MESH: GTP Phosphohydrolases, Ubiquitin-Protein Ligases, MESH : Male, MESH: F-Box Proteins, MESH: Multivariate Analysis, MESH : Kaplan-Meier Estimate, Young Adult, Predictive Value of Tests, Proto-Oncogene Proteins, Internal medicine, medicine, Genetic Predisposition to Disease, Membrane Proteins/genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/classification/genetics/mortality/therapy, Proportional Hazards Models, 030304 developmental biology, business.industry, MESH: Time Factors, PTEN Phosphohydrolase, Membrane Proteins, MESH : Multivariate Analysis, GTP Phosphohydrolases/genetics, MESH: Male, MESH: Proto-Oncogene Proteins, Proto-Oncogene Proteins/genetics, MESH: Gene Deletion, Multivariate Analysis, biology.protein, MESH : ras Proteins, business
Abstract: Purpose The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. Patients and Methods In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). Results N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). Conclusion These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
Published: 2013
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19. Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study

Author: Marie-Christiane Vekemans, Martine Escoffre, Norbert Ifrah, Hervé Dombret, Delphine Rea, Aline Tanguy-Schmidt, Xavier Thomas, Sandrine Hayette, Philippe Rousselot, André Delannoy, Yves Chalandon, Jean-Paul Vernant, Jean-Yves Cahn, Françoise Huguet, Jean-Michel Cayuela, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Laboratoire central d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Biologie Moléculaire, Hospices Civils de Lyon (HCL), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hôpital de Jolimont, Haine-Saint-Paul and Cliniques Universitaires St Luc, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Edouard Herriot [CHU - HCL]
Subjects: Oncology, Male, Time Factors, medicine.medical_treatment, MESH: Piperazines, Hematopoietic stem cell transplantation, Acute lymphoblastic leukemia, MESH: Philadelphia Chromosome, Piperazines, MESH: Unrelated Donors, MESH: Benzamides, 0302 clinical medicine, hemic and lymphatic diseases, Philadelphia Chromosome, ddc:616, Philadelphia Chromosome Positive, MESH: Middle Aged, Stem cell transplantation, Age Factors, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Follow-Up Studies, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Transplantation, Autologous, 3. Good health, Survival Rate, Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/therapy, 030220 oncology & carcinogenesis, Benzamides, Imatinib Mesylate, Female, Unrelated Donors, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH: Survival Rate, Pyrimidines/administration & dosage/adverse effects, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Philadelphia chromosome, Transplantation, Autologous, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Survival rate, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Age Factors, Transplantation, MESH: Humans, business.industry, MESH: Time Factors, Imatinib, Benzamides/administration & dosage/adverse effects, MESH: Adult, medicine.disease, Piperazines/administration & dosage/adverse effects, MESH: Male, Surgery, Clinical trial, Imatinib mesylate, Pyrimidines, MESH: Pyrimidines, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Antineoplastic Agents/administration & dosage/adverse effects, business, MESH: Female, 030215 immunology, Follow-Up Studies
Abstract: International audience; We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response).
Published: 2013
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20. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial

Author: Carine, Domenech, Xavier, Thomas, Sylvie, Chabaud, Andre, Baruchel, François, Gueyffier, Françoise, Mazingue, Anne, Auvrignon, Selim, Corm, Herve, Dombret, Patrice, Chevallier, Claire, Galambrun, Françoise, Huguet, Faezeh, Legrand, Françoise, Mechinaud, Norbert, Vey, Irène, Philip, David, Liens, Yann, Godfrin, Dominique, Rigal, Yves, Bertrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Children's Cancer Center, The Royal Children's Hospital, Hematology (IPC-Marseille), Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Erythrocytes, Adolescent, MESH: Drug Delivery Systems, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, Drug Administration Schedule, MESH: Dose-Response Relationship, Drug, Young Adult, MESH: Bioreactors, Bioreactors, Drug Delivery Systems, MESH: Child, Asparaginase, Humans, MESH: Asparaginase, Child, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Drug Carriers, MESH: Humans, MESH: Middle Aged, Dose-Response Relationship, Drug, MESH: Erythrocytes, MESH: Child, Preschool, Infant, MESH: Adult, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Infant, MESH: Male, MESH: Drug Carriers, MESH: Young Adult, Child, Preschool, MESH: Antineoplastic Agents
Abstract: International audience; l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .
Published: 2011
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21. UV radiation exposure, skin type and lymphoid malignancies: results of a French case-control study

Author: Pierre Soubeyran, Françoise Huguet, Denis Hémon, Laurent Orsi, Xavier Troussard, Gerald Marit, Laure Grandin, Jacqueline Clavel, Christian Berthou, Pierre Fenaux, Alain Monnereau, Noel Milpied, Michel Leporrier, Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Hôpital Morvan, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, 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 Hôtel Dieu Nantes, Hôtel Dieu, Secretariat, U754, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], and CHU Bordeaux [Bordeaux]
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Skin type, Ultraviolet Rays, Lymphoproliferative disorders, Skin Pigmentation, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, UV Radiation Exposure, medicine, Humans, UV radiation exposure, 030212 general & internal medicine, Hair Color, Multiple myeloma, Aged, Hematology, Eye Color, business.industry, Case-control study, Middle Aged, medicine.disease, Lymphoproliferative Disorders, 3. Good health, Lymphoma, skin type and lymphoma, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, 030220 oncology & carcinogenesis, Immunology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract: International audience; OBJECTIVES: Investigating the relationship between skin type, UV exposure, and lymphoid malignancies (LM). METHODS: We conducted a hospital-based case-control study in France, including 813 incident cases of non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), lymphoproliferative syndrome (LPS) or multiple myeloma and 748 controls. RESULTS: Positive associations between HL and blond/red hair (OR = 1.8 [0.8-3.8]), very fair/fair skin (OR = 1.6 [1.0-2.5]) were observed. High propensity to burn was associated with HL (OR = 1.5 [1.0-2.2]) and LPS (OR = 1.4 [1.0-2.1]). Poor ability to tan was significantly associated with HL (OR = 1.7 [1.0-2.8]). Having light hair with high propensity to burn was associated with NHL (OR = 1.5 [0.9-2.5]) and significantly with HL (OR = 3.4 [1.4-8.4]). Having dark hair with high propensity to burn was significantly associated with LPS (OR = 1.5 [1.0-2.2]). The associations with HL and NHL were significant for men only, with significant interactions. Outdoors activities since leaving school or in the last decade were not related to LM. Only an almost negative trend was observed. Prior exposure to artificial UV was not associated with LM. CONCLUSION: These results suggest a positive association between the most reactive and palest skin types and NHL or HL in men and do not rule out a slight negative relationship between UV exposure and LM.
Published: 2008
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22. Occupation and lymphoid malignancies: results from a French case-control study

Author: Michel Leporrier, Alain Monnereau, Pierre Soubeyran, Laurent Orsi, Xavier Troussard, Gerald Marit, Jacqueline Clavel, Denis Hémon, Noel Milpied, Christian Berthou, Françoise Huguet, Pierre Fenaux, Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Hôpital Morvan, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'Hématologie Hôtel Dieu Nantes, Hôtel Dieu, CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Secretariat, U754, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Employment, Male, Oncology, medicine.medical_specialty, Adolescent, case-control study, lymphoma, farming, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, immune system diseases, Internal medicine, Immunopathology, hemic and lymphatic diseases, Epidemiology, medicine, Humans, Occupations, Risk factor, Multiple myeloma, Aged, risk, business.industry, Incidence, Public Health, Environmental and Occupational Health, Case-control study, Cancer, Odds ratio, occupational exposure, Middle Aged, medicine.disease, 030210 environmental & occupational health, 3. Good health, Lymphoma, Surgery, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, 030220 oncology & carcinogenesis, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Multiple Myeloma, business
Abstract: International audience; OBJECTIVES: Investigating relationships between potential occupational risk factors and lymphoid malignancy (LM). METHODS: We conducted a multicenter hospital-based case-control study in France between 2000 and 2004, including 824 incident cases of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma, and "lymphoproliferative syndrome" and 752 frequency-matched controls. Data were collected through face-to-face standardized and detailed interviews. RESULTS: Farming was significantly associated with NHL (odds ratio [OR] = 1.4 [1.0 to 2.0]) and, although not significantly, with lymphoproliferative syndrome and multiple myeloma. ORs were higher for longest durations of exposure. Self-declared exposure to pesticides was significantly associated with NHL (OR = 1.8 [1.2 to 2.7]) and HL (OR = 2.2 [1.0 to 4.7]). Neither solvent-related jobs nor self-reported exposure to solvents were related to LM. Systematic screening based on job titles did not evidence any other association. CONCLUSIONS: The results support the hypothesis that farming plays a role in most types of LM.
Published: 2007
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23. Les chaires des facultés de lettres et de sciences en France au XIXe siècle

Author: Noguès, Boris, Savoirs (LARHRA SAVOIRS), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), En collaboration avec Françoise Huguet, INRP., Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: Chaires, France, XIXe siècle, [SHS.HIST]Humanities and Social Sciences/History, facultés de lettres et de sciences
Abstract: Édition électronique, mise en ligne 2011, aujourd'hui sur le site du LARHRA http://facultes19.ish-lyon.cnrs.fr/prof_facultes_1808_1880.htm
Published: 2011

24. Répertoire des professeurs des facultés des lettres et des sciences en France (1808-1880)

Author: Noguès, Boris, Savoirs (LARHRA SAVOIRS), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Collaboration avec Françoise Huguet, INRP, Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: des facultés des lettres et des sciences, Professeurs, France, [SHS.HIST]Humanities and Social Sciences/History, 1808-1880
Abstract: Édition électronique, mise en ligne 2011. http://facultes19.ish-lyon.cnrs.fr/index.php
Published: 2011

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24 results on '"Françoise Huguet"'

1. Frontline Consolidation with Blinatumomab for High-Risk Philadelphia-Negative Acute Lymphoblastic Adult Patients. Early Results from the Graall-2014-QUEST Phase 2

2. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients

3. Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL

4. Influence of major BCR-ABL1 transcript subtype on outcome in patients with chronic myeloid leukemia in chronic phase treated frontline with nilotinib

5. Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation

6. Outcome of AML patients with IDH2 mutations in real world before the era of IDH2 inhibitors

7. DNMT3A mutation is associated with increased age and adverse outcome in adult T-acute lymphoblastic leukemia

8. The odyssee study: prevention of dysbiosis complications with autologous fecal microbiota transfer (fmt) in acute myeloid leukemia (aml) patients undergoing intensive treatment: results of a prospective multicenter trial

9. Ponatinib evaluation and safety in real-life chronic myelogenous leukemia patients failing more than two tyrosine kinase inhibitors: the PEARL observational study

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

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

12. Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study

13. CML patients show sperm alterations at diagnosis that are not improved with imatinib treatment

14. Recommandations 2015 du France Intergroupe des Leucémies Myéloïdes Chroniques pour la gestion du risque d'événements cardiovasculaires sous nilotinib au cours de la leucémie myéloïde chronique

15. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study

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

17. Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic Malignancies

18. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

19. Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study

20. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial

21. UV radiation exposure, skin type and lymphoid malignancies: results of a French case-control study

22. Occupation and lymphoid malignancies: results from a French case-control study

23. Les chaires des facultés de lettres et de sciences en France au XIXe siècle

24. Répertoire des professeurs des facultés des lettres et des sciences en France (1808-1880)

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