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113 results on '"Feugier, A."'

1. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis

Author: Roberta Di Blasi, Steven Le Gouill, Emmanuel Bachy, Guillaume Cartron, David Beauvais, Fabien Le Bras, François-Xavier Gros, Sylvain Choquet, Pierre Bories, Pierre Feugier, Olivier Casasnovas, Jacques Olivier Bay, Mohamad Mohty, Magalie Joris, Thomas Gastinne, Pierre Sesques, Jean-Jacques Tudesq, Laetitia Vercellino, Franck Morschhauser, Elodie Gat, Florence Broussais, Roch Houot, Catherine Thieblemont, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Hospices Civils de Lyon (HCL), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Carnot Lymphome (CALYM), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), CHU Pontchaillou [Rennes], 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: Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Biochemistry
Abstract: Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure
Published: 2022
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2. Quelles sont les situations propices à l'utilisation de la téléconsultation en médecine générale ? Points de vue médecins et patients

Author: Pagliero, Séléna, Feugier, Amandine, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Jenny Forte, and Romain Lutaud
Subjects: Patients, Médecine générale, [SDV]Life Sciences [q-bio], Acuité des besoins du patient, Signes et symptômes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Téléconsultation
Abstract: Introduction : La pandémie de Covid-19, ayant débuté en Europe et en France au début de l’année 2020, a favorisé l’essor considérable de la téléconsultation.Plusieurs études menées dans divers pays montrent que cette pratique se généralise, avec une place de choix au sein des nouvelles politiques de santé publique, mais soulève plusieurs problématiques. L’une des principales étant l’absence d’examen clinique. L’objectif de notre étude était de déterminer les motifs les plus propices à l’utilisation de la téléconsultation en médecine générale, du point de vue des médecins et des patients. Cette étude, en miroir médecins-patients, présentait une première partie qualitative qui permettait de dégager les différents motifs de téléconsultation, ainsi qu’une seconde partie quantitative, détaillée dans ce document.Matériel et méthodes : Un questionnaire était adressé par mail, par téléphone, ou par courrier, à l’ensemble des médecins généralistes thésés, installés ou remplaçants, exerçant dans la ville de Marseille ou dans le département du Vaucluse. Les patients étaient inclus soit par le biais d’affiches distribuées aux médecins et affichées en salle d’attente, soit directement sur proposition de leur médecin. Chaque participant notait les 15 motifs de téléconsultation mis en évidence dans la partie qualitative de l’étude selon une échelle de pertinence (allant de 1: motif pas du tout adapté, à 10: motif totalement adapté).Résultats : 131 personnes ont répondu au questionnaire (65 médecins et 66 patients). Les motifs jugés les plus adaptés pour la téléconsultation étaient : prescription et interprétation des examens complémentaires, dossier administratif, contraception et dépistage des IST.Conclusion : Dans cette étude, les motifs semblant les plus propices à la téléconsultation en médecine générale sont ceux ne nécessitant pas obligatoirement un examen clinique, d’autant plus si le médecin généraliste a déjà réalisé antérieurement une consultation en présentiel. Médecins et patients semblent s’accorder sur ces notions.
Published: 2022

3. Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study

Author: Emmanuel Bachy, Roch Houot, Pierre Feugier, Krimo Bouabdallah, Reda Bouabdallah, Emmanuelle Nicolas Virelizier, Marie Maerevoet, Christophe Fruchart, Sylvia Snauwaert, Steven Le Gouill, Jean-Pierre Marolleau, Lysiane Molina, Cécile Moluçon-Chabrot, Catherine Thieblemont, Hervé Tilly, Fontanet Bijou, Corinne Haioun, Eric Van den Neste, Bettina Fabiani, Michel Meignan, Guillaume Cartron, Gilles Salles, Olivier Casasnovas, Franck Morschhauser, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Innovative Leukemia Organization (Filo), CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CH Dunkerque, Department of ENT surgery, AZ Sint Jan Brugge Oostende, Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), L’Héma-NexT [UNIV Nantes] (i-Site NexT), Université de Nantes (UN), Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, 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, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), 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), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cliniques Universitaires Saint-Luc [Bruxelles], Service de neurophysiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Weill Medical College of Cornell University [New York], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Lille, The study was funded by the LYSARC, and financially supported in part by investigator-initiated study grants from Celgene/BMS and Roche., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Microenvironnement des niches tumorales [UNIV Tours] (CNRS GDR 3697 MicroNiT), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de gastro-entérologie, and UCL - (SLuc) Unité d'oncologie médicale
Subjects: Adult, Neutropenia, Adolescent, [SDV]Life Sciences [q-bio], Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Antibodies, Monoclonal, Humanized, Biochemistry, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Lenalidomide, Lymphoma, Follicular
Abstract: Obinutuzumab and lenalidomide (referred to as the GALEN combination) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥18 years had an Eastern Cooperative Oncology Group performance status ≤2 and high-tumor burden, grade 1 to 3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8, 15, and 22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/d, days 1-21, cycle 1; days 2-22, cycles 2-6) for six 28-day cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary end point was complete response rate (CRR) after induction per the 1999 International Working Group criteria. From October 2015 to February 2017, a total of 100 patients were enrolled. CRR after induction was 47%, and the overall response rate (ORR) was 92%. Post hoc analyses per the 2014 Lugano classification, including patients with missing bone marrow assessments, identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and an ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free survival and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any grade; 47% grade ≥3). Only 2% of patients presented with febrile neutropenia; others were mainly grade ≤2. No other specific grade ≥3 toxicity occurred at a frequency >3%. Overall, these results showed promising clinical efficacy for the chemotherapy-free GALEN backbone in previously untreated patients with high tumor burden FL. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered at clinicaltrials.gov as #NCT01582776.
Published: 2022
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4. TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia

Author: Lazarian, Grégory, Theves, Floriane, Hormi, Myriam, Letestu, Rémi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frédéric, Delabesse, Eric, Estienne, Marie-Hélène, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cédric, Poulain, Stéphanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valérie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Aurran, Thérese, Herbaux, Charles, Cartron, Guillaume, Dartigeas, Caroline, Delmer, Alain, Dupuis, Jehan, Dilhuydy, Marie, Ferrant, Emmanuelle, Feugier, Pierre, Genevieve, Franck, de Guibert, Sophie, Guieze, Romain, Leblond, Véronique, Levy, Vincent, Leprêtre, Stephane, Merabet, Fatiha, Michallet, Anne-Sophie, Nguyen-Khac, Florence, Quinquenel, Anne, Raynaud, Sophie, Re, Daniel, Thieblemont, Catherine, Tournillhac, Olivier, Troussard, Xavier, Truchan-Graczyk, Malgorzata, Willems, Lise, Ysebaert, Loic, Zini, Jean-Marc, 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, Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service d'Hématologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 biologique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'Oncologie Génétique [Rouen] (CLCC Henri Becquerel), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire Bio-Santis, Cavaillon, France, Laboratoire d'oncobiologie [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Génétique Médicale (CHU de Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hématologie biologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie Cellulaire [Hospices civils de Lyon], Hospices Civils de Lyon, Lyon, France, Hospices Civils de Lyon (HCL), Service de Cytogénétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Mort cellulaire programmée et résistance aux drogues dans les hémopathies malignes = Cell death and Drug Resistance in Hematological Disorders [CRC], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Uppsala University, French Innovative Leukemia Organization (Filo), Cancéropole Ille de France. Grant Number: 2019-1-EMERG-22-INSERM 6-1, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Mutation, Humans, Chlorambucil, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Tumor Suppressor Protein p53, Codon, Leukemia, Lymphocytic, Chronic, B-Cell, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022
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5. Pesticide-Free Robotic Control of Aphids as Crop Pests

Author: Virginie Lacotte, Toan NGuyen, Javier Diaz Sempere, Vivien Novales, Vincent Dufour, Richard Moreau, Minh Tu Pham, Kanty Rabenorosoa, Sergio Peignier, François G. Feugier, Robin Gaetani, Thomas Grenier, Bruno Masenelli, Pedro da Silva, Abdelaziz Heddi, Arnaud Lelevé, Leleve, Arnaud, Contrôle automatisé sans pesticides des pestes de l'agriculture - - GREENSHIELD2017 - ANR-17-CE34-0012 - AAPG2017 - VALID, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ampère, Département Automatique pour l'Ingénierie des Systèmes (AIS), Ampère (AMPERE), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Greenshield, Institut des Nanotechnologies de Lyon (INL), Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INL - Matériaux Fonctionnels et Nanostructures (INL - MFN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), ANR, ANR Greenshield, and ANR-17-CE34-0012,GREENSHIELD,Contrôle automatisé sans pesticides des pestes de l'agriculture(2017)
Subjects: robotics, [SPI.AUTO] Engineering Sciences [physics]/Automatic, Complementary and alternative medicine, [SDV.SA.STA]Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of agriculture, farming, aphid detection, laser-based neutralization, deep learning, image-based visual servoing, Pharmaceutical Science, [SDV.SA.STA] Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of agriculture, Pharmacology (medical), [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract: International audience; Because our civilization has relied on pesticides to fight weeds, insects, and diseases since antiquity, the use of these chemicals has become natural and exclusive. Unfortunately, the use of pesticides has progressively had alarming effects on water quality, biodiversity, and humanhealth. This paper proposes to improve farming practices by replacing pesticides with a laser-based robotic approach. This study focused on the neutralization of aphids, as they are among the most harmful pests for crops and complex to control. With the help of deep learning, we developeda mobile robot that spans crop rows, locates aphids, and neutralizes them with laser beams. We have built a prototype with the sole purpose of validating the localization-neutralization loop on a single seedling row. The experiments performed in our laboratory demonstrate the feasibility ofdetecting different lines of aphids (50% detected at 3 cm/s) and of neutralizing them (90% mortality) without impacting the growth of their host plants. The results are encouraging since aphids are one of the most challenging crop pests to eradicate. However, enhancements in detection and mainly intargeting are necessary to be useful in a real farming context. Moreover, robustness regarding field conditions should be evaluated.
Published: 2022
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6. Economic Burden in Non-Hodgkin Lymphoma Survivors: The French Lymphoma Study Association SIMONAL Cross-Sectional Study

Author: Nerich, Virginie, Guyeux, Christophe, Henry-Amar, Michel, Couturier, Raphael, Thieblemont, Catherine, Ribrag, Vincent, Tilly, Hervé, Haioun, Corinne, Casasnovas, René-Olivier, Morschhauser, Franck, Feugier, Pierre, Sibon, David, Ysebaert, Loic, Nicolas-Virelizier, Emmanuelle, Broussais-Guillaumot, Florence, Damaj, Gandhi L, Jais, Jean-Philippe, Salles, Gilles, Woronoff-Lemsi, Macha, Mounier, Nicolas, and Femto-st, DISC
Subjects: [INFO.INFO-ET] Computer Science [cs]/Emerging Technologies [cs.ET], [INFO.INFO-SE] Computer Science [cs]/Software Engineering [cs.SE], [INFO.INFO-DC] Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], [INFO.INFO-IU] Computer Science [cs]/Ubiquitous Computing, [INFO.INFO-MA] Computer Science [cs]/Multiagent Systems [cs.MA], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-CR] Computer Science [cs]/Cryptography and Security [cs.CR]
Abstract: No study has focused on the economic burden in non-Hodgkin lymphoma (NHL) survivors, even though this knowledge is essential. This study reports on health care resource use and associated health care costs as well as related factors in a series of 1671 French long-term NHL survivors. METHODS: Health care costs were measured from the payer perspective. Only direct medical costs (medical consultations, outpatient treatments, hospitalizations, and medical transport) in the past 12 months were included (reference year 2015). Multiple linear regression was used to search for explanatory factors of health care costs. RESULTS: In total, 1100 survivors (66%) reported having used at least 1 health care resource, and 867 (52%) reported having used at least 1 outpatient treatment. After the authors accounted for missing data, the mean health care cost was estimated at €702 ± €2221. Hospitalizations and outpatient treatments were the main cost drivers. Sensitivity analyses confirmed the robustness of the results. For the 1100 survivors who reported using at least 1 health care resource, the mean health care cost was €1067 ± €2268. Several factors demonstrated statistically significant relationships with health care costs. For instance, cardiovascular disorders increased costs by 66% ± 16%. In contrast, rituximab or autologous stem cell transplantation as initial therapy had no effect on health care costs. CONCLUSIONS: The consideration of economic constraints in health care is now a reality. This retrospective study reports on a better understanding of health care resource use and associated health care costs as well as related factors. It may help health care professionals in their ongoing efforts to design personcentered health care pathways.
Published: 2022

7. Clinical, biological, and molecular genetic features of Richter syndrome and prognostic significance: a study of the French Innovative Leukemia Organization

Author: Reiner Siebert, Anne Quinquenel, Romain Guieze, Catherine Thieblemont, Frederic Davi, Caroline Dartigeas, Sébastien Hergalant, Mathilde Hunault, Florence Cymbalista, Christof Schneider, Marie-Christine Béné, Cécile Tomowiak, Thomas Remen, Kamel Laribi, Damien Roos-Weil, Julien Broséus, Gregory Lazarian, Francis Guillemin, Odile Blanchet, Florian Bouclet, Elise Chapiro, Eugen Tausch, Stephan Stilgenbauer, Sandra Lomazzi, Florence Nguyen-Khac, Pierre Feugier, Charline Moulin, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Reims (CHU Reims), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Ulm - Ulm University [Ulm, Allemagne], Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, 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 de Ressources Biologiques - [Nancy] (CRB Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hergalant, Sébastien, and 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)
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Richter syndrome, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hematology, medicine.disease, Prognosis, Survival Analysis, 3. Good health, [STAT] Statistics [stat], [STAT]Statistics [stat], Leukemia, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Mutation, Disease Progression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Lymphoma, Large B-Cell, Diffuse, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract: International audience
Published: 2021
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8. Obinutuzumab versus Rituximab in young patients with advanced DLBCL, a PET-guided and randomized phase 3 study by LYSA

Author: Le Gouill, Steven, Ghesquieres, Hervé, Obéric, Lucie, Morschhauser, Franck, Tilly, Herve, Ribrag, Vincent, Lamy, Thierry, Thieblemont, Catherine, Maisonneuve, Herve Gerard, Gressin, Remy, Bouabdallah, Krimo, Haioun, Corinne, Damaj, Gandhi, Fornecker, Luc-Matthieu, Bouabdallah, Reda, Feugier, Pierre, Sibon, David, Cartron, Guillaume, Bonnet, Christophe, André, Marc, Chartier, Loic, Ruminy, Philippe, Kraeber-Bodere, F, Bodet-Milin, C, Berriolo-Riedinger, Alina, Briere, Josette, Jais, Jean-Philippe, Molina, Thierry, Itti, Emmanuel, Casasnovas, Olivier, Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), 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 Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Hôpital Michallon, CHU Pessac, CHI Créteil, 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, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU UCL Namur, The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Hopital Saint-Louis [AP-HP] (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), Jonchère, Laurent, UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: [SDV] Life Sciences [q-bio], [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV]Life Sciences [q-bio], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: International audience; Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.
Published: 2021
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9. Real-world outcomes following venetoclax therapy in patients with chronic lymphocytic leukemia or Richter syndrome: a FILO study of the French compassionate use cohort

Author: Sophie de Guibert, Lauren Veronese, Loic Ysebaert, Charles Herbaux, Olivier Tournilhac, Emmanuelle Tchernonog, Anne-Sophie Michallet, Florence Cymbalista, Damien Roos-Weil, Bruno Pereira, Jehan Dupuis, Pierre Feugier, Anne Calleja, Florian Bouclet, Caroline Dartigeas, Sandy Amorim, Anaise Blouet, Marie-Sarah Dilhuydy, Florence Nguyen-Khac, Pierre Morel, Nataliya Dmytruck, Kamel Laribi, Alain Delmer, Thérèse Aurran, Bénédicte Hivert, Romain Guieze, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), and FAYE, Fatimata
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Compassionate Use Trials, Male, medicine.medical_treatment, Chronic lymphocytic leukemia, Abnormal Karyotype, Kaplan-Meier Estimate, Targeted therapy, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Medicine, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Sulfonamides, Hematology, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, Progression-Free Survival, 3. Good health, Tumor lysis syndrome, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, France, Lymphoma, Large B-Cell, Diffuse, Adult, medicine.medical_specialty, Antineoplastic Agents, Infections, 03 medical and health sciences, Internal medicine, Complex Karyotype, Humans, Aged, Retrospective Studies, business.industry, Venetoclax, medicine.disease, Bridged Bicyclo Compounds, Heterocyclic, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell, chemistry, Drug Evaluation, business, Tumor Lysis Syndrome, 030215 immunology
Abstract: The BCL2 inhibitor venetoclax is transforming the management of patients with chronic lymphocytic leukemia (CLL), given its high efficacy in relapsed/refractory CLL as observed in both early-phase and randomized clinical trials. The present study aimed to determine whether venetoclax is effective and well tolerated in patients with CLL or Richter's syndrome (RS) in a real-world setting and to highlight factors impacting survival. Data from a venetoclax French compassionate use program were collected for 67 patients (60 with CLL and 7 with RS). Most patients presented adverse genetic features, such as TP53 disruption (74%) or complex karyotype (58%). Tumor lysis syndrome was observed in 14 (22%) patients, and 16 (24%) patients were hospitalized for grade III/IV infection. In the CLL cohort, ORR was 75 %, 1-year PFS was 61% (95% CI = 47-72%) and 1-year OS 70% (95% CI = 56-80%). No impact of TP53 disruption was noted while complex karyotype was identified as a predictor of both inferior PFS (HR = 3.46; 95% CI = 1-12; log-rank p = 0.03) and OS (HR = 3.2; 95% CI = 0.9-11.4, log-rank p = 0.047). Among the seven patients with RS, two achieved an objective response to venetoclax; however, the median OS was only 1.1 month. The well-balanced safety/efficacy profile of venetoclax is confirmed in this real-world setting. Complex karyotype should be evaluated as a predictive factor of survival for patients treated by venetoclax.
Published: 2021
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10. Facteurs pronostiques clinico-biologiques et génomiques de la survie dans le syndrome de Richter

Author: H. Busby, H. Auge, A. Quinquenel, F. Bouclet, Charline Moulin, S. Lomazzi, Romain Guièze, D. Roos-Weil, P Feugier, C. Dartigeas, C. Tomowiak, J. Broséus, Florence Cymbalista, S. Hergalant, M.-C. Béné, Francis Guillemin, R. Morizot, T. Remen, K. Laribi, E. Tausch, C. Thieblemont, S. Stilgenbauer, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), CHU Clermont-Ferrand, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie 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, Centre Hospitalier Le Mans (CH Le Mans), and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 030505 public health, Epidemiology, Public Health, Environmental and Occupational Health, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 3. Good health, [STAT]Statistics [stat], 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, 0305 other medical science, ComputingMilieux_MISCELLANEOUS
Abstract: Etat de la question Le syndrome de Richter (SR) correspond a la transformation d’une leucemie lymphoide chronique en un lymphome agressif, principalement lymphome B diffus a grandes cellules (LBDGC). Ses facteurs pronostiques sont partiellement connus. Notre etude devait confirmer/identifier des caracteristiques cliniques, biologiques et genomiques pronostiques de la survie du SR sous-type LBDGC. Materiel et methodes Parmi 103 patients de 10 centres francais presentant un SR sous-type LBDGC, 58 etaient identifies avec un materiel au diagnostic de qualite suffisante pour etudier la valeur pronostique d’un panel de 13 genes. Nous avons realise un modele de regression a risques proportionnels de Cox puis un modele flexible en appliquant une fonction spline sur la variable performance status selon l’« Eastern Cooperative Oncology Group » (PS ECOG) qui n’etait graphiquement pas proportionnelle dans le temps Resultats La mediane de survie globale (SG) etait de 8 mois. En analyse bivariee, les patients avec PS ECOG > 1, ceux avec des plaquettes 1, profil non mute du gene des chaines lourdes des immunoglobulines (IGVH) et anomalie de TP53 ( Tableau 1 ). En appliquant une fonction spline sur le PS ECOG, son effet sur la survie se limitait aux 12 mois suivant le diagnostic : le hazard ratio estime de facon lineaire avant et apres 12 mois pour faciliter son interpretation etait respectivement 3,98 et 1,04 (intervalle de confiance 95 % 1,79–8,82 et 0,26–4,16 ; p = 0,001 et 0,96). Conclusion Le profil IGVH non mute est identifie comme nouveau facteur pronostique, en plus du PS ECOG, du taux de plaquettes et du statut TP53 sur la biopsie de SR. L’effet du PS ECOG est limite aux 12 mois suivant le diagnostic.
Published: 2021
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11. Reduced acute graft-versus host disease incidence in patients receiving anti-T lymphocyte globulin (ATLG) in comparison to anti-thymocyte globulin (ATG) for the prophylaxis of graft-versus-host disease after allogeneic haematopoietic stem cell transplantation

Author: Campidelli, Arnaud, d'Aveni, Maud, Moulinet, Charline, Detrait, Marie, Boulangé, Laura, Roth Guépin, Gabrielle, Tarillon, Sylvie, Hottier, Nathalie, Jeulin, Helene, Verstraete, Emma, Notarantonio, Anne-Béatrice, Feugier, Pierre, Rubio, Marie-Thérèse, and Rubio, Marie Therese
Subjects: [SDV] Life Sciences [q-bio], [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: Both anti-T-lymphocyte globulin (ATLG-grafalon) and anti-thymocyte globulin (ATG-thymoglobulin) can prevent acute and chronic graft-versus-host-disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). Because of distinct production characteristics, ATG and ATLG dysplay distinct affinities to T and other immune cells in vitro. Whether these differences could impact post-transplant outcomes has never been explored.MethodsIn this monocentric retrospective study, we compared post-transplant outcomes of 114 patients transplanted between January 2017 and September 2020 for an hematological malignancy with peripheral blood stem cells from a matched HLA 10/10 related (MRD, n= 25) or unrelated donor (MUD, n=89) and receiving either ATG (5 mg/kg; n=50) or ATLG (15 mg/kg for MRD and 30 mg/kg for MUD, n=64) for GVHD prophylaxis. We also compared naive and memory T cell subset, regulatory T and invariant NKT cell reconstitution after transplantation between the two groups. ResultsThe comparison of patients’ characteristics at transplantation showed that the two groups were comparable in terms of disease type (64% of AML and MDS in both groups), disease risk index (intermediate in 68% vs 71% in the ATG and ATG groups, respectively, p=0.6), CMV status and of donor (78% of MUD in both groups). Patients were older in the ATLG group (mean age 56 vs 51 years, p=0.04) and received more frequently a reduced intensity/toxicity conditioning regimen (72% vs 46%, p=0.01). Since ATLG was used more recently in our center, the median follow-up was longer in the ATG group (21 months vs 8.5 months, p< 0.001). At day 180, the cumulative incidence (CI) of grade II-IV acute GVHD was 49% (95% CI 34-64%) in the ATG vs 25% (95% CI 12-33%) in ATLG group, (p=0.005) (Figure 1). CI of CMV (p=0.98) and EBV (p=0.43) reactivations were comparable between the 2 groups. Incidence of chronic GVHD was similar in both groups (62% vs 72%, in the ATG vs ATLG groups at 2 years) with low incidences of moderate and severe cGVHD (29% vs 19 %, in the ATG vs ATLG groups at 2 years). At one year post-HSCT, non relapse mortality was comparable between the 2 groups (9% in both), while relapse incidence was higher in the ATG group (40% vs 16%, in the ATG vs ATLG groups, p= 0.016). At 2 years, extrapolated overall and GVHD-free, relapse free survival (GRFS) were not significantly different between the 2 groups (61% vs 71% and 54% vs 67% in the ATG vs ATLG groups, respectively). In terms of immune reconstitution, we observed was a more profound depletion of naive CD4 and CD8 T cells and reduced PD1 expressing on CD8 T cells in patients receiving ATLG in comparison to those receiving ATG between day 14 and day 90 post-HSCT while levels of regulatory cells were similar.ConclusionOur results suggest that ATLG may better prevent the occurrence of severe acute GVHD by differential effect on T cell reconstitution and activation, without increasing the incidence of relapse and of viral reactivation. These results should be confirmed in a prospective randomized trial.
Published: 2021

12. Large-Scale Proteomics Identifies Distinct Signatures for Richter Syndrome and De Novo Diffuse Large B-Cell Lymphoma: A French Study from the Filo Group

Author: Christine Carapito, Florian Bouclet, Veronique Leblond, Anne Quinquenel, Cécile Tomowiak, Catherine Thieblemont, Romain Piucco, Pierre Feugier, Aurore Perrot, Marie C. Béné, Caroline Dartigeas, Hélène Busby, Sébastien Hergalant, Florence Cymbalista, Romain Guieze, Luc Mathieu Fornecker, Stephan Stilgenbauer, Sandra Lomazzi, Romain Morizot, Hélène Augé, Julien Broséus, Eugen Tausch, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Universitätsklinikum Ulm - University Hospital of Ulm, Service de Pathologie [CHRU Nancy], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), 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), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Richter syndrome, Scale (ratio), Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Proteomics, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Cell Biology, Hematology, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], 030220 oncology & carcinogenesis, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: Richter syndrome (RS) occurs during the disease course of 2 to 10% of Chronic Lymphocytic Leukemia (CLL). Diffuse Large B-Cell Lymphoma (DLBCL) subtype accounts for 90-95% of RS cases. While presenting with the same morphology as de novo DLBCLs, DLBCL subtype of RS is associated with a very poor outcome. Proteins are the primary cellular biological effectors. Proteome composition is highly dependent on regulatory mechanisms located both upstream and downstream translation (transcriptional regulation, post-translational modifications, protein metabolism). Thus, the analysis of the genome and the transcriptome only allows a putative extrapolation of the expressed proteome. Proteomic studies have been performed in the context of de novo DLBCLs (Fornecker et al. Sci Rep. 2019), unravelling a set of proteins associated with refractoriness. In CLL, it showed different profiles according to IGHV mutational status after B-Cell Receptor activation (Perrot et al. Blood 2011). No proteomic study of RS has been carried out to date. RS sample selection was performed across 7 French institutions affiliated to the FILO (French Innovative Leukemia Organization). A total of 49 fresh frozen biopsies were collected, including 28 de novo DLBCLs and 21 RS, mostly treated with first line R-CHOP. All biopsies were centrally reviewed. RS samples were characterized, with data on CLL-RS clonal relationship and mutational status for a 13-gene panel representing the most frequently mutated genes in CLL. Only DLBCL subtype RS samples with at least 50% tumor purity (range 50-95%) and a minimum 10 mg weight were selected. Peptide measurements were performed using liquid chromatography coupled with tandem mass spectrometry, according to published methods (Muller et al. Sci Rep. 2018). Stringent quality controls were applied to ensure sample integrity, abundance accuracy and overall reproducibility. Proteome reconstruction at peptide and at protein level was achieved with a specifically devised pipeline involving conditional filtering, full normalization, categorization and imputation of missing values. These tools made use of the R/Bioconductor DEP package (Zhang et al. Nat Protoc. 2018). Supervised (Bayesian linear models) and unsupervised (hierarchical clustering, K-means, PCA) analyses were further applied to identify differential protein signatures. These were functionally annotated with ReactomePA (Yu et al. Mol Biosyst. 2016) for pathways and STRING (Szklarczyk et al. Nucleic Acids Res. 2019) for association networks. Extended proteomics analysis identified 1,772 proteins, among which 191 were differentially expressed (False Discovery Rate/FDR < 0.05) in RS samples compared to de novo DLBCLs, with 82 increased and 109 decreased proteins. Hierarchical clustering revealed a highly correlated expression profile of these top candidates and clearly separated the 21 RS and the 28 de novo DLBCL samples (Figure 1). Sample distribution was independent from chemosensitivity/resistance, for DLBCL samples, and also unrelated to GCB/Non-GCB phenotype according to Hans algorithm, Epstein-Barr virus positivity or tumor purity. Functional interactome is an in silico protein-protein interaction network built on published data from the literature and available in public databases. The functional interactome computed from the 82 proteins overexpressed in RS showed a strongly enriched association network (protein-protein interactions; p-value < 1e-16), with an over-representation in BCR pathway, VEGF signaling, JAK-STAT pathway and Interleukin-12, Rho GTPase, and actin coiling (FDR < 0.05; Figure 1). Proteins underexpressed in RS (109) also displayed highly associated interactions (p-value < 1e-16) with a main node including proteins involved in cell death regulation, extracellular matrix organization, regulation of Insulin Growth Factor, and signaling by receptor tyrosine kinase (FDR < 0.05; Figure 1). Here we performed proteomics on a 49-sample cohort of 28 de novo DLBCLs and 21 RS, which revealed a specific and differential signature in RS. This includes increased expression of targets within the druggable signaling pathways BCR and JAK-STAT. Furthermore the decrease in proteins involved in cell death regulation and extracellular matrix organization suggests resistance mechanisms to apoptosis and immune system in RS. Disclosures Dartigeas: Janssen: Honoraria; Roche: Honoraria; Gilead: Other: non-financial support. Tausch:AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding. Leblond:AstraZeneca: Consultancy, Honoraria; Lilly: Consultancy; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Gilead: Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau. Thieblemont:Hospira: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Incyte: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bayer: Honoraria. Stilgenbauer:Mundipharma: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding. Guieze:abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Perrot:Amgen, BMS/Celgene, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding. Feugier:astrazeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; gilead: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria, Research Funding. Broséus:AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Gilead: Honoraria.
Published: 2020
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13. Clinico-Biological, Molecular and Prognostic Features of Patients with Diffuse Large B-Cell Lymphoma-Variant of Richter Syndrome: A Multicenter Retrospective Study of the French Innovative Leukemia Organization

Author: Romain Guieze, Thomas Remen, Julien Broséus, Catherine Thieblemont, Stephan Stilgenbauer, Sandra Lomazzi, Eugen Tausch, Florian Bouclet, Hélène Busby, Kamel Laribi, Veronique Leblond, Marie C. Béné, Florence Cymbalista, Caroline Dartigeas, Sébastien Hergalant, Cécile Tomowiak, Romain Morizot, Hélène Augé, Charline Moulin, Francis Guillemin, Anne Quinquenel, Pierre Feugier, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'Hématologie [CHRU Nancy], Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pathologie [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), 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), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and 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)
Subjects: Oncology, medicine.medical_specialty, Richter syndrome, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], business.industry, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, [STAT]Statistics [stat], Leukemia, business, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: Richter Syndrome (RS) corresponds to the transformation of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) into an aggressive lymphoma, in most cases a Diffuse Large B-Cell Lymphoma (DLBCL). RS outcome is variable and still poorly understood. The aim of our study was to analyze the clinical, biological and molecular features liable to predict survival in a retrospective series of newly diagnosed RS from the French Innovative Leukemia Organization (FILO). From 10 French centers, 103 biopsy-confirmed DLBCL subtype RS, diagnosed from 2001 to 2019, were identified. Fresh-frozen biopsies (FB) were available in 58 cases. All biopsies were centrally reviewed. Clinical and biological characteristics at CLL and RS diagnoses including cytogenetics, clonal relationship with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) according to the Hans algorithm, RS prognostic scores (Tsimberidou et al. J Clin Oncol. 2006, Rossi et al. Blood 2011) as well as treatment and outcomes were collected. Targeted next generation sequencing was used on RS FB for the following gene set: TP53, ATM, SF3B1, NOTCH1, BIRC3, FBXW7, RPS15, EGR2, MYD88, XPO1, POT1, BRAF, and NFKBIE. Overall Survival (OS) was defined as time from RS diagnosis until the date of death or end of follow-up and analyzed using Kaplan-Meier method. Multivariable analysis was performed using Cox regression model for variables with a p-value Clinical and biological characteristics and outcomes were broadly similar between the full 103-patient cohort and the subset of 58 patients with available gene mutation data. The latter only was considered for the subsequent analyses. The median age at CLL/SLL diagnosis was 60 (range 34-81) and 39 patients (67.2%) were male. Prior to RS, 24 (41.38%) received more than 1 line of treatment for CLL. The median time to transformation was 5 years (range 0-22). The median OS from RS diagnosis was 8 months (Figure 1a). The median age at RS diagnosis was 65.5 years (range 42-87). ECOG Performance Status (PS) was >1 in 29/53 patients (54.8%) and 32/56 (57.1%) had a Bulky disease. Elevated Lactate DeHydrogenase (LDH) levels (≥ 1.5N) were found in 38/49 patients (77.6%). Unmutated IGHV was observed in 45/58 (77.6%) RS samples. CLL and RS were clonally related for 29/33 (87.9%) RS with available IGHV sequence at CLL diagnosis. TP53 disruption was detected in 34/56 (60.7%) RS cases including TP53 mutations in 23/58 (39.7%). According to Tsimberidou et al., 10/46 (21.7%) RS were in the low-risk group, 10 in the low-intermediate risk group, 11 (23.9%) in the high-intermediate risk group and the other 15 in the high-risk group. According to the Rossi score, only 4/51 RS (7.8%) were low risk, and 19 (37.3%) and 28 (54.9%) intermediate and high-risk, respectively. The most frequent treatment for RS was R-CHOP-like regimen [38/56 (67.9%)], 5 and 2 patients received autologous or allogeneic stem cell transplantation respectively. Most patients, 40/56 (71.4%) failed to reach complete remission after the first line. By bivariate analysis (Figure 1b-e), ECOG PS, platelet count and TP53 disruption worsened OS (p1, platelet count RS outcome is poor. Here, we focused specifically on Richter cells on diagnostic biopsies for genetic analyses. Unmutated IGHV status was identified as prognostic factor for RS, in addition to the previously described: ECOG PS, platelet count and TP53 disruption. More molecular studies are necessary to increase knowledge about RS and improve the survival of patients with DLBCL-type RS. Disclosures Dartigeas: Janssen: Honoraria; Roche: Honoraria; Gilead: Other: non-financial support. Tausch:Roche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding. Leblond:Roche: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Amgen: Honoraria; AstraZeneca: Consultancy, Honoraria; Lilly: Consultancy. Thieblemont:Incyte: Honoraria; Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Hospira: Research Funding; Bayer: Honoraria. Laribi:abbvie: Honoraria, Research Funding; amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding. Stilgenbauer:F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Guieze:abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Feugier:gilead: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding. Broséus:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Gilead: Honoraria.
Published: 2020
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14. A phenomenological and multiscale modeling of arterial growth and remodeling under endofibrosis

Author: J. Jansen, Fabien S. Godeferd, X. Escriva, P. Feugier, Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, 0206 medical engineering, Biomedical Engineering, Hemodynamics, Lumen (anatomy), Bioengineering, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Arterial wall, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], ComputingMilieux_MISCELLANEOUS, business.industry, [SPI.FLUID]Engineering Sciences [physics]/Reactive fluid environment, [SPI.PLASMA]Engineering Sciences [physics]/Plasmas, 030229 sport sciences, General Medicine, 020601 biomedical engineering, Multiscale modeling, Computer Science Applications, Human-Computer Interaction, medicine.anatomical_structure, Cardiology, Vascular pathology, Thickening, business, human activities, Artery
Abstract: High level endurance sports, like biking, may lead to a vascular pathology called endofibrosis. Its symptoms are an arterial wall thickening and a reduction of the artery lumen calibre. Cyclists ar...
Published: 2020
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15. Caractérisation du profil protéomique du Syndrome de Richter

Author: Romain Piucco, Romain Morizot, Luc-Matthieu Fornecker, Pierre Feugier, Sébastien Hergalant, Julien Broséus, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Proteomics, Protéome, Diffuse Large B-cell Lymphoma, Syndrome de Richter, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Leucémie Lymphoïde Chronique, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic Lymphocytic Leukemia, Lymphome B Diffus à Grandes Cellules, Richter syndrome, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: National audience; Le Syndrome de Richter (SR) correspond au développement d’un lymphome secondaire agressif chez les patients présentant une Leucémie Lymphoïde Chronique (LLC). Il possède un phénotype Lymphome B Diffus à Grandes Cellules (LBDGC) dans 90-95 % des cas et se caractérise par une morphologie semblable aux LBDGC primaires avec un phénotype immunohistochimique non-GC dans 90 % des cas. Du fait de sa complexité et de sa chimiorésistance, le pronostic du SR reste sombre. Le protéome est constitué par l’ensemble des protéines. C’est une unité complexe et dynamique qui va varier en fonction des conditions biologiques. Les analyses du domaine protéomique se sont popularisées ces dernières années avec le développement de la spectrométrie de masse en tandem (SDM MS/MS) permettant l’acquisition d’un jeu de données conséquent mais impliquant une multitude de biais (grande hétérogénéité, valeurs manquantes, seuils de détection) à intégrer dans les analyses, avec l’aide de la bioinformatique.Pour la première fois, une étude protéomique a été réalisée par SDM couplée à la chromatographie en phase liquide (LC-MS/MS) en stratégie « bottom-up » de tumeurs ganglionnaires de 21 patients atteints du SR, 9 atteints de Lymphomes B Diffus à Grandes Cellules (LBDGC) primaires chimioréfractaires, 19 LBDGC primaires chimiosensibles et 10 LBDGC secondaires hors SR. Un protocole bioinformatique permettant une reconstruction efficace et une analyse statistique du protéome tant au niveau peptidique que protéique a été mis en place. Cette approche a permis la quantification fine de 1772 protéines et 11385 peptides dans les 59 échantillons. Les analyses statistiques ont mis en lumière 206 protéines et 1437 peptides (correspondant à 271 protéines) différentielles (FDR < 0,05) dans le SR comparativement aux autres LBDGC. L’exploration de ces données a permis de mettre en évidence des protéines impliquées dans la signalisation liée au B-Cell Receptor (BCR), à la mort cellulaire, la matrice extracellulaire et l’inflammation. L’existence de deux profils protéomiques du SR différents est également décrite.Cette étude contribue ainsi à une meilleure compréhension des mécanismes physiopathologiques du SR, permettant l’ouverture de potentielles nouvelles voies thérapeutiques tout en apportant de nouvelles données distinguant le SR des LBDGC primitifs chimioréfractaires et des LBDGC secondaires.
Published: 2020

16. Characteristics of Lymphoma in Patients with Inflammatory Bowel Disease: A Systematic Review

Author: Tunay Kökten, Pierre Feugier, Ndeye Coumba Ndiaye, Silvio Danese, Catherine Thieblemont, Laurent Beaugerie, Rémi Houlgatte, Laurent Peyrin-Biroulet, Djésia Arnone, Julien Broséus, Marie Muller, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie [CHRU Nancy], 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 de Gastroentérologie et nutrition [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), and Humanitas Clinical and Research Center [Rozzano, Milan, Italy]
Subjects: medicine.medical_specialty, Lymphoma, [SDV]Life Sciences [q-bio], Population, Follicular lymphoma, Lymphoproliferative disorders, Gastroenterology, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, MALT lymphoma, General Medicine, medicine.disease, Inflammatory Bowel Diseases, Prognosis, digestive system diseases, 3. Good health, Lymphatic system, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Complication, business
Abstract: Background Lymphoma is a dreaded complication of inflammatory bowel diseases [IBD]. Knowledge about lymphoma in patients with IBD is limited to epidemiological data and the description of risk factors. We performed a systematic review to describe the clinical characteristics and prognosis of lymphoma in patients with IBD. Methods Electronic databases were searched up to June 1, 2020. All published clinical characteristics of lymphoma occurring in patients with IBD were collected. Results Eleven studies were included. A total of 589 lymphomas were described in patients with IBD. As seen in de novo lymphoma, non-Hodgkin’s lymphoma [NHL] was the most common histological subtype [83.9%]. Diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma were the most well-represented NHL in patients with IBD [30% and 13% respectively]. Two main differences were observed in comparison with de novo lymphoma: primary intestinal lymphoma [PIL] represented a large proportion of lymphoma in patients with IBD [22–75%] whereas mucosa-associated lymphoid tissue [MALT] lymphoma was under-represented. Epstein–Barr virus [EBV]-positive status was observed in a large proportion of tumours [44–75%]. Survival data of lymphoma in patients with IBD were similar to those of de novo lymphoma. Discussion This systematic review first highlights that PIL [especially DLBCL subtype] is significantly more frequent in patients with IBD and represents the most common entity. Conversely, MALT lymphoma is extremely rare in the IBD population. However, the overall quality of the evidence is low. Further studies are required to better define lymphoma characteristics in patients with IBD.
Published: 2020
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17. Maintien à long terme d’une réponse complète avec maladie résiduelle indétectable après une stratégie de traitement combinant de l’ibrutinib à une immunochimiothérapie ≪ adaptée ≫ chez les patients atteints d’une leucémie lymphoïde chronique non antérieurement traitée

Author: Michallet, A.S., Dilhuydy, M.S., Subtil, F., Rouille, V., Mahé, B., Laribi, K., Villemagne, B., Salles, G., Tournilhac, O., Delmer, A., Leblond, V., Tomowiak, C., FORNECKER, L.M., Letestu, R., Lévy, V., Cymbalista, F., Ysebaert, Loic, Dartigeas, C., Aurran, T., Lepretre, S., Le Garff-Tavernier, M., Ticchioni, M., Aanaei, C., Nguyen-Khac, F., Banos, A., Carassou, P., Cartron, G., Truchan-Graczyk, M., Portois, C., Pegourie, B., Feugier, P., Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: 11-03; International audience
Published: 2020

18. Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study

Author: Hervé Tilly, Thierry Fest, Loic Ysebaert, Sylvie Glaisner, Guillaume Cartron, Rene-Olivier Casasnovas, Steven Le Gouill, Jean-Claude Eisenmann, Roch Houot, Marie-Hélène Delfau-Larue, Marie-Laure Boulland, Gilles Salles, Gian Matteo Pica, Franck Morschhauser, Asma Beldi-Ferchiou, François Lemonnier, Pierre Feugier, Luc Xerri, Pascal Godmer, Vincent Ribrag, Hervé Maisonneuve, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pontchaillou [Rennes], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Henri Mondor, Centre Hospitalier Métropole Savoie [Chambéry], 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), 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), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CRLCC René Huguenin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, 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 Montpellier, 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), Bernardo, Elizabeth, CHU Henri Mondor [Créteil], and 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)
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Lymphoma, Follicular, 030304 developmental biology, 0303 health sciences, Chemotherapy, Lymphoid Neoplasia, business.industry, Hematology, medicine.disease, Prognosis, Minimal residual disease, 3. Good health, Lymphoma, Regimen, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Rituximab, Bone marrow, business, medicine.drug
Abstract: Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701). The objective of the minimal residual disease (MRD) analysis was to determine the ability of a chemotherapy-free regimen to induce CMR. Of 440 French patients participating in the Lymphoma Study Association (LYSA) RELEVANCE MRD study, all 222 patients with a BIOMED-2–detectable BCL2-JH translocation at diagnosis were analyzed. MRD was quantified by droplet digital polymerase chain reaction with a sensitivity ≤10−4. At week 24 (end of induction treatment), 98% and 78% of patients achieved CMR in peripheral blood (PB) and bone marrow (BM), respectively. Achievement of CMR (in PB and/or BM) had a significant impact on progression-free survival (PFS), with 3-year PFS of 84% and 55% for patients with CMR and detectable MRD, respectively (P = .015). CMR at week 24 was reached more frequently in the R2 arm (105/117; 90%) than in the R-Chemo arm (70/90; 77%) (P = .022). The poor prognostic value in terms of PFS for the persistence of molecular disease was observed irrespective of treatment arm (interaction test, P = .31). In agreement with the clinical results of the RELEVANCE trial, our results show that R2 immunomodulatory treatment in first-line FL can achieve high rates of CMR.
Published: 2020
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19. A meta-analysis of outcomes of in situ reconstruction after total or partial removal of abdominal infected aortic graft

Author: Batt, Michel, Camou, Fabrice, Coffy, Amandine, Feugier, Patrick, Senneville, Eric, Caillon, Jocelyne, Calvet, Brigitte, Chidiac, Christian, Laurent, Frédéric, Revest, Matthieu, Daures, Jean Pierre, For Vascular Graft Infection, Research Group, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Hôpital Saint-André, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Département de chirurgie vasculaire, Hospices Civils de Lyon (HCL), Département des Maladies Infectieuses [CH Tourcoing] (Hôpital Gustave Dron), Centre Hospitalier de Tourcoing-Centre Hospitalier Gustave Dron [Tourcoing], Centre hospitalier universitaire de Nantes (CHU Nantes), CH Béziers, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Gustave Dron [Tourcoing]-Centre Hospitalier de Tourcoing, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience
Published: 2020
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20. A Polymer-Free Paclitaxel-Eluting Stent Versus a Bare-Metal Stent for De Novo Femoropopliteal Lesions The BATTLE Trial

Author: Gouëffic, Yann, Sauguet, Antoine, Desgranges, Pascal, Feugier, Patrick, Rosset, Eugenio, Ducasse, Eric, Kaladji, Adrien, Salomon Du Mont, Lucie, Pernès, Jean Marc, Commeau, Philippe, Lermusiaux, Patrick, Leclere, Brice, Guyomarc’h, Béatrice, Hoffmann, Clément T., Maurel, Blandine, Physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur, Clinique Pasteur [Toulouse], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Chirurgie Thoracique Vasculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes], CHU Pontchaillou [Rennes], Service de Chirurgie vasculaire - Médecine vasculaire (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut du thorax, Service de chirurgie thoracique et cardio vasculaire [Brest] (CCTV - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV]Life Sciences [q-bio]
Published: 2020
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21. Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC®

Author: Hachem, Mayssa, Nacir, Houda, Picq, Madeleine, Belkouch, Mounir, Bernoud-hubac, Nathalie, Windust, Anthony, Meiller, Laure, Sauvinet, Valerie, Feugier, Nathalie, Lambert-porcheron, Stephanie, Laville, Martine, Lagarde, Michel, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), ROSSI, Sabine, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)
Subjects: Male, Erythrocytes, Time Factors, Docosahexaenoic Acids, genetic structures, brain, gas chromatography combustion isotope ratio, Administration, Oral, Biological Availability, plasma phospholipids, lcsh:TX341-641, gas chromatography combustion isotope ratio mass spectrometry, Article, Gas Chromatography-Mass Spectrometry, Double-Blind Method, Humans, Triglycerides, Aged, Cross-Over Studies, food and beverages, Middle Aged, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), France, lcsh:Nutrition. Foods and food supply, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of 13C-labeled DHA after oral intake of a single dose of 13C-AceDoPC®, in comparison with 13C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the 13C enrichment of DHA-containing lipids. 13C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, 13C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the 13C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion.
Published: 2020
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22. Diagnosis and Treatment of Chronic Lymphocytic Leukemia: Recommendations of the French CLL Study Group (FILO)

Author: Anne Quinquenel, Olivier Tournilhac, Stéphane Leprêtre, Aline Clavert, Thérèse Aurran-Schleinitz, Anne-Sophie Michallet, Vincent Levy, Caroline Dartigeas, Florence Cymbalista, Xavier Troussard, Luc-Matthieu Fornecker, Alain Delmer, Cécile Tomowiak, Florence Nguyen-Khac, Pierre Feugier, Rémi Letestu, Frederic Davi, Loic Ysebaert, David Ghez, Sophie de Guibert, Kamel Laribi, Romain Guieze, Veronique Leblond, Marie-Sarah Dilhuydy, 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: Richter syndrome, Pediatrics, medicine.medical_specialty, Chronic lymphocytic leukemia, MEDLINE, Relapsed CLL, 03 medical and health sciences, 0302 clinical medicine, Daily practice, hemic and lymphatic diseases, Guideline Article - Expert opinion, medicine, ComputingMilieux_MISCELLANEOUS, lcsh:RC633-647.5, business.industry, Autoimmune Cytopenia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, medicine.disease, 3. Good health, Leukemia, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract: As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.
Published: 2020
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23. Bariatric surgery affects obesity-related protein requirements

Author: Karem Slim, Yves Boirie, N. Lyon, M. Robert, M. Miolanne, Adeline Blot, B. Pereira, Christelle Guillet, E. Disse, N. Feugier, C. Louvet, N. Farigon, Martine Laville, P. Le Ruyet, A. Mishellany-Dutour, A. Masgrau, A. Caille, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), LACTALIS RECHERCHE ET DEVELOPPEMENT (LACTALIS R&D), Groupe Lactalis, Service de Nutrition Clinique [CHU Clermont-Ferrand], and CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: 0301 basic medicine, Nitrogen balance, Sleeve gastrectomy, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Protein requirements, Population, Gastric Bypass, 030209 endocrinology & metabolism, Context (language use), Urine, 03 medical and health sciences, 0302 clinical medicine, Recovery, Humans, Medicine, Longitudinal Studies, Prospective Studies, Temporal change, Obesity, education, Nutrition, Bariatric surgery, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Protein requirement, medicine.disease, Obesity, Morbid, Surgery, Cross-Sectional Studies, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Summary Context Following bariatric surgery, protein deficiency intakes are reported in morbidly obese patients, whereas post-bariatric protein requirements are not specifically defined with validated method in this population. Objective To assess average protein requirement (APR) in obese subjects, before, 3 months and 12 months after bariatric surgery using the validated method of nitrogen balance. Design and setting Prospective longitudinal study conducted in 21 morbidly obese patients (BMI 43.9 ± 1.4 kg/m2) before (M0), 3 months (M3) and 12 months (M12) after sleeve gastrectomy or Roux-en-Y gastric by-pass. An additional larger cross-sectional study was performed to validate APR before surgery in non-operated matched obese patients (n = 106). APR was evaluated at M0, M3, M12 by measuring 3 days dietary intakes together with losses of nitrogen in urine and stools. Main outcome measure APR was defined as the mean value of protein intake required to achieve balance nitrogen equilibrium. Results Before surgery, APR in morbidly obese patients was 0.76 [95%CI, 0.66–0.92] g/kg Body Weight (BW)/d in the experimental group, and 0.74 [0.70–0.80] g/kg BW/d in the validation group. APR was 0.62 [0.51–0.75] g/kg/d at M3 and 0.87 [0.75–0.98] g/kg/d at M12, with no difference between surgical procedures. Spontaneous protein intakes were respectively 0.80 ± 0.05, 0.43 ± 0.03 and 0.71 ± 0.04 g/kg BW/d respectively at M0, M3 and M12. Conclusion This study demonstrates a temporal change in protein requirement after bariatric surgery whatever the type of surgery. Spontaneous protein intakes following bariatric surgery does not cover protein requirements for most patients, suggesting that specific dietary protein recommandations have to be adapted in obese patients with bariatric surgery. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT01249326.
Published: 2020
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24. Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

Author: Alexandre Paccalet, Laura Mechtouff, Emmanuelle Canet-Soulas, Nicolas Costes, Stephane Luong, Antoine Millon, Yves Berthezène, Patrick Feugier, Thomas Bochaton, Salim Si-Mohamed, Claire Crola Da Silva, Alexandre Bani-Sadr, Didier Le Bars, Norbert Nighoghossian, Monica Sigovan, Diane Collet-Benzaquen, David Magne, Adeline Mansuy, Julie Haesebaert, Philippe Douek, Jérémie Tordo, and Hospices Civils de Lyon, Departement de Neurologie (HCL)
Subjects: medicine.diagnostic_test, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Magnetic resonance imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, medicine.disease, Asymptomatic, Culprit, 030218 nuclear medicine & medical imaging, body regions, 03 medical and health sciences, Stenosis, 0302 clinical medicine, Carotid artery plaque, medicine, Mineral metabolism, Radiology, Nuclear Medicine and imaging, Tomography, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Nuclear medicine, Stroke, ComputingMilieux_MISCELLANEOUS
Abstract: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. We included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. 18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.
Published: 2020
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25. Maintenance of Long-Term Undetectable Minimal Residual Disease after Combination of Ibrutinib with Abbreviated Chemotherapy in the Icll-07 Filo Trial

Author: Anne Banos, Vincent Levy, Magali Le Garff-Tavernier, Veronique Leblond, Sophie de Guibert, Valérie Rouille, Loic Ysebaert, Philippe Carassou, Bruno Villemagne, Kamel Laribi, Alain Delmer, Frederique Orsini, Beatrice Mahe, Michel Ticchioni, Gilles Salles, Marie-Sarah Dilhuydy, Thérèse Aurran, Carmen Aanaei, Florence Nguyen-Khac, Brigitte Pegourie, Rémi Letestu, Fabien Subtil, Luc Mathieu Fornecker, Caroline Dartigeas, Jean Pierre Vilque, Cécile Tomowiak, Guillaume Cartron, Florence Cymbalista, Margot Truchan, Anne-Sophie Michallet, Christelle Portois, Pierre Feugier, Olivier Tournilhac, Stéphane Leprêtre, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Chemotherapy regimen, Minimal residual disease, 3. Good health, Fludarabine, chemistry, Ibrutinib, Rituximab, business, 030215 immunology, medicine.drug
Abstract: Introduction In previously untreated, medically fit patients with chronic lymphocytic leukaemia (CLL) and no 17p deletion, there is current research interest in improving survival outcomes and potentially sparing some patients from the standard 6 cycles of fludarabine, cyclophosphamide and rituximab (FCR). The phase II ICLL-07 (NCT02666898) trial, conducted by the French Innovative Leukemia Organization (FILO), aimed to explore the efficacy of obinutuzumab and ibrutinib treatment induction for 9 months, followed by a minimal residual disease (MRD)-driven strategy. Methods Following assessment at Month 9, patients in complete response (CR) with bone marrow (BM) MRD ResultsBetween 10/2015 and 05/2017, 135 patients were enrolled. At Month 9, only 8% of patients reached CR with BM MRD Conclusion These findings from the ICLL-07 trial demonstrated that, in previously untreated, medically fit patients with CLL and no 17p deletion, treatment induction with obinutuzumab and ibrutinib followed by an MRD-driven strategy yielded a high rate of CR with BM and PB MRD Disclosures Salles: Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events. Leblond:Gilead: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Cymbalista:Sunesis: Research Funding; Roche: Research Funding; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria. Le Garff-Tavernier:Alexion: Consultancy, Honoraria. Letestu:Alexion: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Roche: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.
Published: 2019

26. What Is the Secondary Patency of Thrombosed Bypasses of the Lower Limbs Cleared by Fibrinolysis In Situ?

Author: Myriam Ammi, Patrick Feugier, Jean Picquet, Tchala Kassegne, Samir Henni, Nellie Della Schiava, and Université d'Angers (UA)
Subjects: Male, medicine.medical_specialty, Time Factors, Secondary patency, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Risk Assessment, Amputation, Surgical, 030218 nuclear medicine & medical imaging, Blood Vessel Prosthesis Implantation, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Recurrence, Risk Factors, Fibrinolysis, medicine, Humans, Thrombolytic Therapy, Survival rate, Vascular Patency, Aged, Retrospective Studies, Urokinase, business.industry, Graft Occlusion, Vascular, Thrombosis, Retrospective cohort study, General Medicine, Middle Aged, Limb Salvage, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Lower Extremity, Amputation, Adjunctive treatment, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: In case of acute thrombosis, lower limb bypasses can, in certain cases, be cleared by local intra-arterial fibrinolysis (LIF). The aim of this study is to evaluate the secondary patency of thrombosed bypasses after fibrinolysis.This retrospective study includes all patients hospitalized for thrombosed bypasses of the lower limbs that were treated with in situ fibrinolysis using urokinase, between 2004 and 2013, in 2 French university hospital centers. Fibrinolysis was indicated in case of recent thrombosis (3 weeks) provoking acute limb ischemia without sensory-motor deficit and in the absence of general contraindications. The secondary patency of the grafts was defined as the time after fibrinolysis without a new thrombotic event.There were 207 patients, hospitalized for recent thrombosis of 244 bypasses. The LIF was efficient in 74% of the cases (n = 180). Secondary patency of these bypasses was 54.2% and 32.4% overall, 68.3% and 50.3% for the suprainguinal bypasses, and 48.3% and 21.5% for the infrainguinal bypasses at 1 and 5 years, respectively. There is a significant difference (P = 0.002) regarding the permeability of the suprainguinal and infrainguinal bypasses. The survival rate was 75% (±6.4%) at 5 years and the limb salvage rate was 89% (±3.3%), 78.2% (±5.1%), and 75% (±5.8%) at 1, 3, and 5 years, respectively. The only independent factor influencing the secondary patency of infrainguinal bypasses that was significant in a multivariate analysis was the infragenicular localization of the distal anastomosis (P = 0.023).LIF is an effective approach that often allows the identification of the underlying cause, permitting elective adjunctive treatment of the underlying cause. Although LIF is at least as effective as its therapeutic alternatives described in the literature, the secondary patency of the bypasses remains modest and encourages close monitoring, particularly in patients with an infragenicular bypass.
Published: 2019
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27. Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study

Author: Vincent Levy, Marie-Sarah Dilhuydy, Gregory Lazarian, Anne Quinquenel, Rémi Letestu, Carole Fleury, Delphine Nollet, Florence Cymbalista, Luc-Matthieu Fornecker, Damien Roos-Weil, Alain Delmer, Katia Hormigos, Lise Willems, Romain Guieze, Anne-Sophie Michallet, Loic Ysebaert, Pierre Feugier, Fanny Baran-Marszak, Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, 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), CHU Bordeaux [Bordeaux], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Universités (COMUE), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), CHADEYRON, DOMINIQUE, 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: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Lymphocytosis, Chronic lymphocytic leukemia, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Bruton's tyrosine kinase, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Leukemia, chemistry, Specimen collection, 030220 oncology & carcinogenesis, Ibrutinib, Cohort, biology.protein, Sample collection, medicine.symptom, business
Abstract: Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cγ2 (PLCG2) genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a “snapshot” of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 109/L, enabling next-generation sequencing (NGS); BTK and PLCG2 mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a BTK mutation was significantly associated with subsequent CLL progression (P = .0005 vs no BTK mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment.
Published: 2019
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28. Vénétoclax dans la LLC en rechute ou réfractaire : une étude FILO de la cohorte ATU en France

Author: Bouclet, F., Calleja, A., Dihuydy, M.S., Amorim, S., Cymbalista, F., Herbaux, C., De Guibert, S., Roos-Weil, D., Hivert, B., Aurran, T., Dupuis, J., Blouet, A., Tchernonog, E., Laribi, K., Dmytruck, N., Morel, Pierre, Michallet, A.S., Dartigeas, C., Farnault, L., Lavaud, A., Plantier, I., Bay, Jacques‐Olivier, Tournilhac, Olivier, Delmer, A., Feugier, P., Ysebaert, Loic, Guiéze, Romain, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: 04-77; International audience
Published: 2019

29. Taux élevé de réponse complète (RC) avec maladie résiduelle (MRD) indétectable dans la moelle après une stratégie d’épargne de chimiothérapie guidée par la MRD en première ligne de traitement dans la leucémie lymphoïde chronique (LLC)

Author: Michallet, A.S., Dilhuydy, M.S., Subtil, F., Rouille, V., Laribi, K., Villemagne, Bruno, Tournilhac, Olivier, Leblond, V., Delmer, A., Cymbalista, F., Letestu, R., Lévy, V., Nguyen-Khac, F., Lepretre, S., Feugier, P., Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: 04-05; International audience
Published: 2019

30. Test fonctionnel de la p53 et corrélation avec la délétion 17p et/ou les mutations de TP53 dans la leucémie lymphoïde chronique. Résultats du protocole ICLL001 BOMP sous l’égide du groupe FILO

Author: Le Garff-Tavernier, M., Quiney, C., Véronèse, Lauren, Nguyen-Khac, F., Robbe, P., Combes, P., Dihuydy, M.S., Feugier, P., Mahé, B., Sanhes, L., Delmer, A., Ysebaert, Loic, Truchan-Graczyk, M., Dreyfus, B., Choquet, S., Aurran, T., Ferrant, E., Dartigeas, C., Lepretre, S., Pica, G.M., Davi, F., Pereira, Bruno, Delepine, R., Schuh, A., Guiéze, Romain, Bay, Jacques‐Olivier, Leblond, V., Merle-Béral, H., De Guibert, S., Tournilhac, Olivier, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, 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: [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: 04-19; International audience
Published: 2019

31. Clinical and Biological Characteristics and Outcomes of Richter Transformation: A French Multicenter Study from the Filo Group

Author: Marie C. Béné, Pierre Feugier, Julien Broséus, Caroline Dartigeas, Anne Quinquenel, Romain Guieze, Hélène Augé, Hélène Busby, Florence Cymbalista, Thomas Remen, Sandra Lomazzi, Charline Moulin, Cécile Tomowiak, Marion Divoux, Catherine Thieblemont, Veronique Leblond, Florian Bouclet, Romain Morizot, CHADEYRON, DOMINIQUE, 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: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Chronic lymphocytic leukemia, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Univariate analysis, Richter transformation, business.industry, Venetoclax, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Regimen, chemistry, Ibrutinib, business, Idelalisib, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.
Published: 2019

32. Obinutuzumab plus Lenalidomide (GALEN) for the treatment of relapse/refractory aggressive lymphoma a phase II LYSA study

Author: Emmanuelle Nicolas-Virelizier, Koen Van Eygen, Roch Houot, Eric Van Den Neste, Lysiane Molina, Achiel Van Hoof, Hervé Tilly, Guillaume Cartron, Gilles Salles, Rene-Olivier Casasnovas, Franck Morschhauser, Christophe Fruchart, Christophe Bonnet, Pierre Feugier, Steven Le Gouill, Krimo Bouabdallah, Pierre Zachee, Marc André, Marie Maerevoet, Fontanet Bijou, Corinne Haioun, Sophie de Guibert, Philippe Ruminy, Cécile Moluçon-Chabrot, Jonchère, Laurent, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), 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 Nantes (CHU Nantes), 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), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Cliniques Universitaires Saint-Luc [Bruxelles], Algemeen Ziekenhuis Groeninge Hospital, Centre Hospitalier Universitaire de Liège (CHU-Liège), 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), ZNA Stuivenberg, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Léon Bérard [Lyon], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), and Bernardo, Elizabeth
Subjects: Oncology, Male, Cancer Research, Lymphoma, [SDV]Life Sciences [q-bio], Aggressive lymphoma, Angiogenesis Inhibitors, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Agents, Immunological, Obinutuzumab, immune system diseases, Recurrence, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Lenalidomide, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Hematology, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Monoclonal, Female, medicine.drug, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diffuse large B cell lymphoma, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Refractory, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Animals, Humans, neoplasms, Aged, Mantle cell lymphoma, business.industry, medicine.disease, Clinical trial, chemistry, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: International audience; Lenalidomide is a potent immunomodulatory agent that has demonstrated clinical activity in the treatment of both diffuse large B cell lymphomas (DLBCL) and mantle cell lymphomas (MCL). In relapsed/refractory (R/R) DLBCL, two large prospective studies evaluating lenalidomide monotherapy demonstrated an overall response rate (ORR) of 28% (N = 108) and 27.5% (N = 51), respectively [1, 2]. In patients with R/R MCL patients, lenalidomide induced an ORR of 40% (N = 170) [3, 4]. In 2013, the FDA approved lenalidomide for the treatment of R/R MCL. Obinutuzumab is a unique type II glycoengineered monoclonal anti-CD20 antibody (Ab) with increased ADCC and increased direct cell death induction compared to rituximab. In monotherapy, obinutuzumab demonstrated efficacy in patients with MCL and DLBCL [5]. The ORR after treatment with obinutuzumab monotherapy was 28% and 27% in R/R DLBCL and MCL, respectively [5]. Furthermore, the combination of lenalidomide and rituximab (R 2 regimen) demonstrated promising efficacy in patients with follicular lymphoma (FL) [6, 7], MCL [8, 9], and DLBCL [10-13]. We hypothesized that the combination of obinutuzumab (GA) with lenalidomide (LEN) might be even more efficient while retaining a good safety profile. In a phase I B study, we previously identified 20 mg/day as the recommended dose (RD) of lenalidomide in * Franck Morschhauser
Published: 2019
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33. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

Author: Richard Delarue, Emmanuelle Nicolas-Virelizier, Reda Bouabdallah, Veronique Edeline, Bertrand Joly, Adrian Tempescul, Hassan Farhat, Luc-Matthieu Fornecker, Peggy Dartigues, René-Olivier Casasnovas, Laurent Martin, Franck Morschhauser, Aspasia Stamatoullas, Pauline Brice, Marc André, Alain Delmer, Michel Meignan, Nicolas Mounier, Hervé Ghesquières, Jehan Dupuis, Philippe Quittet, Krimo Bouabdallah, Julien Lazarovici, Alina Berriolo-Riedinger, Anne-Claire Gac, Alexandra Traverse-Glehen, Pierre Feugier, Thierry Lamy, Thomas Gastinne, Hervé Maisonneuve, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Henri Mondor, 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, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Sud Francilien, CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Département de biologie et pathologie médicales [Gustave Roussy], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Nice (CHU Nice), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Dijon, Département d'Hematologie, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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], CRLCC Henri Becquerel, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie [Nantes], Hôpital Sud-Fancilien, CH Sud-Fancilien, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie Hôpital Mignot, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CH La Roche-sur-Yon, Service d’Hématologie Clinique [CHU Pontchaillou, Rennes], Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dinant-Godinne UCL Namur, Service de cancérologie, 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 de médecine nucléaire [Créteil], Université Grenoble Alpes (UGA), Département Hématologie (FNCLCC), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Régional d'Etudes sur le CANcer (GRECAN), IFR146-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse )-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département d'Hématologie Clinique [CHU Nantes], Université Mohamed Boudiaf de M'sila, Service d’Hématologie Clinique [CHRU Nancy], Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre hospitalier La Roche-Sur-Yon, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologie morphologique, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Pathologie [CHU de Dijon], Service de Médecine Interne Clermont Ferrand (MéDECINE INTERNE - CLERMONT-FERRAND), Hopital, Hôpital Archet 2 [Nice] (CHU), Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CH Evry-Corbeil, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CCSD, Accord Elsevier, Service d'Hématologie Clinique (CHU de Dijon), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’Hématologie [Rouen], CHU Rouen, Service hématologie Créteil, CHU, Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Département de médecine nucléaire (Institut Curie, Saint-Cloud), Institut Curie [Paris], Hématologie clinique [CH La Roche-sur-Yon], service hématologie Strasbourg, CHU Strasbourg, Service d’Hématologie Clinique [Rennes], Service hématologie Nice, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, CHU Henri Mondor [Créteil], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Male, medicine.medical_specialty, Vincristine, Dacarbazine, [SDV]Life Sciences [q-bio], Salvage therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Procarbazine, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, business.industry, Standard treatment, medicine.disease, Hodgkin Disease, 3. Good health, Vinblastine, Drug Therapy, Computer-Assisted, [SDV] Life Sciences [q-bio], Oncology, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: International audience; Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (
Published: 2019
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34. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial

Author: Petrella , T., Copie-Bergman , C., Brière , J P, Delarue , R., Jardin , F., Ruminy , P., Thieblemont , C., Figeac , M., Canioni , D., Feugier , P., Fabiani , B., Leroy , K., Parrens , M., André , M., Haioun , C., Salles , G. A., Gaulard , P., Tilly , H, Jais , J P, Molina , T J, Petrella , H, Copie-Bergman , H, Delarue , H, Jardin , H, Ruminy , H, Thieblemont , H, Figeac , P, Canioni , H, Feugier , H, Fabiani , H, Leroy , H, Parrens , H, André , H, Haioun , H, Salles , H, Gaulard , H, Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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 ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, Service de pathologie [CHU Necker], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Saint Antoine Paris, CHU Bordeaux [Bordeaux], IRF, Uppsala, Sweden, Service d'hématologie clinique, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine ( UPEC Médecine ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomie pathologique [CHU Necker], Earth and Life Institute [Louvain-La-Neuve], Université Catholique de Louvain ( UCL ), Département de zoologie, Musée royal de l'Afrique centrale [Tervuren], Conservatoire National des Arts et Métiers - Aquitaine ( CNAM Aquitaine ), and Conservatoire National des Arts et Métiers [CNAM] ( CNAM )
Subjects: BCL2, hemic and lymphatic diseases, immunohistochemistry, diffuse large B-cell lymphoma, MYC, prognosis, cell of origin, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract: International audience; Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial.; We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples.; The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81).; Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival.; NCT00144755.
Published: 2017

35. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author: Loic Ysebaert, Anne Banos, Vincent Delwail, Roch Houot, Nicolas Daguindau, Reda Garidi, Margaret Macro, Ghandi Damaj, Bertrand Joly, Jean Pierre Vilque, Sylvain Carras, Mary Callanan, Fabrice Jardin, Marie Pierre Moles, Magda Alexis, Steven Le Gouill, Emmanuelle Tchernonog, Laurent Voillat, Hacene Zerazhi, Christiane Mounier, J. Fleury, Sandy Amorin, Anne Moreau, Jean Michel Pignon, Adrian Tempescul, Véronique Dorvaux, Yazid Arkam, Luc Fornecker, Caroline Dartigeas, Cecile Chabrot, Philippe Solal Celigny, Pierre Feugier, Remy Gressin, Anna Schmitt, Jean Fontan, Clémentine Sarkozy, Nadine Morineau, Jehan Dupuis, Selim Corm, Krimo Bouadallah, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service d'Hématologie [CH Annecy], CH Annecy, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'Hématologie Clinique [CHU Rennes], CHU Pontchaillou [Rennes], Département d’Hématologie Clinique [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'hématologie (CH de Dunkerque), Centre Hospitalier Dunkerque, Service Hématologie [CH Métropole Savoie, Chambery], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital de Bayonne, CH de la Côte Basque, Hématologie de liaison avec Institut de Cancérologie de la Loire [CHU de Saint-Etienne], CHU Saint-Etienne, Centre hospitalier universitaire Henri-Mondor [Créteil], Hôpital Universitaire de Caen, 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), Service d’Hématologie [CHU de Clermont Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d’Hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), 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 hématologie Amiens, CHU Amiens-Picardie, 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 [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service d'Hématologie [Bordeaux], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex-Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Diderot - Paris 7 (UPD7), Hôpital Saint-Quentin, Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital de Corbeil, Service d'Oncologie médicale [Clinique Victor Hugo], Clinique Victor Hugo, Centre Catherine-de-Sienne [Nantes] (CCS), Département d'Hématologie Clinique [CHU d'Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Hopital d'Avignon, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service Hématologie, Mulhouse, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hématologie Biologique [CHR d'Orléans], Centre Hospitalier Régional d'Orléans (CHR), Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Service d'Hématologie [Nantes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Clinique [Rennes], 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, Laboratoire d'Hématologie [CHU Amiens], Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional d'Orléans (CHRO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Bendamustine, Male, medicine.medical_specialty, Time Factors, Non-Hodgkin Lymphoma, Lymphoma, Mantle-Cell, Neutropenia, Gastroenterology, Dexamethasone, Disease-Free Survival, Article, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, Survival rate, Aged, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, Minimal residual disease, 3. Good health, Lymphoma, Survival Rate, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Mantle cell lymphoma, Female, business, 030215 immunology, medicine.drug
Abstract: International audience; We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P
Published: 2018
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36. La chirurgie bariatrique affecte les besoins en protéines liés à l'obésité

Author: Christelle Guillet, Aurelie Masgrau, Mishellany-Dutour, A., Blot, A., Pereira, B., Slim, K., Robert, M., Disse, E., Feugier, N., Leruyet, P., Louvet, C., Miolanne, M., Farigon, N., Goudable, J., Laville, M., Yves Boirie, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine, Délégation à la Recherche Clinique et à l'Innovation (DRCI), Chirurgie digestive, CHU Clermont-Ferrand, Hôpital Edourad Herriot, Hospices Civils de Lyon (HCL), Endocrinologie Diabétologie et Nutrition, Recherche & Développement, EDF (EDF), Centre Hospitalier Jacques Lacarin, Nutrition Clinique, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA), and Centre Hospitalier Universitaire de Clermont-Ferrand
Subjects: [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: FONCTION INTESTINALE ET OBÉSITÉ; Introduction et but de l’étude: Après chirurgie bariatrique, un déficit en protéines est fréquemment rapporté chez les patients souffrant d'obésité morbide alors que les besoins en protéines n’ont pas été précisément déterminés dans cette population. L'objectif de cette étude est d'évaluer le besoin protéique moyen (BPM) chez les sujets obèses, avant, 3 mois et 12 mois après la chirurgie bariatrique en utilisant la méthode de bilan azoté.Matériel et méthodes: Une étude longitudinale prospective, incluant 21 patients en obésité morbide (IMC 43,9±1,4 kg/m²) a été mise en place pour évaluer le bilan azoté calculé à partir des mesures des apports alimentaires et des pertes d'azote dans les urines et les selles collectées durant 3 jours avant (M0), 3 mois (M3) et 12 mois (M12) après sleeve gastrectomie ou by-pass gastrique. Une régression linéaire entre les apports en protéines et le bilan azoté a été utilisée pour déterminer la valeur du BPM. Une étude transversale plus large a été réalisée pour valider le BPM chez des patients obèses appariés non opérés (n = 106). Les valeurs de BPM sont exprimées en moyenne [Intervalle de confiance (IC) à 95%] et les autres valeurs en moyenne ± écart-type à la moyenne.Résultats et Analyse statistique : Avant la chirurgie, le BPM des patients obèses était de 0,76 [IC à 95%, 0,66-0,92] g/kg de poids corporel/j dans le groupe expérimental et de 0,74 [0,70-0,80] g/kg/j dans le groupe de validation. Il était de 0,62 [0,51-0,75] g/kg/j à M3 et de 0,87 [0,75-0,98] g/kg/j à M12, sans différence entre les procédures chirurgicales. Les apports spontanés en protéines étaient respectivement de 0,80±0,05; 0,43±0,03; 0,71±0,04 g/kg/j respectivement à M0, M3 et M12.Conclusion: Cette étude indique un changement temporel des besoins en protéines après chirurgie bariatrique quel que soit le type de chirurgie. Les apports spontanés après chirurgie bariatrique ne couvrent pas les besoins en protéines de la plupart des patients, ce qui suggère que des recommandations spécifiques sur les protéines alimentaires doivent être adaptées chez les patients obèses candidats à une chirurgie bariatrique.
Published: 2018

37. Increased rituximab exposure does not improve response and outcome of patients with chronic lymphocytic leukemia after fludarabine, cyclophosphamide, rituximab. A French Innovative Leukemia Organization (FILO) study

Author: Frédérique Orsini-Piocelle, Alain Delmer, Olivier Tournilhac, Stéphane Leprêtre, Rémi Letestu, Mira Tout, Thérèse Aurran, David Ternant, Sophie de Guibert, Phan Letuan, Emmanuelle Ferrant, Valérie Rouille, Guillaume Cartron, Bruno Villemagne, Pierre Feugier, Boris Guiu, Caroline Dartigeas, Anne Banos, Beatrice Mahe, Jehan Dupuis, Anne-Laure Gagez, Veronique Leblond, 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: Oncology, medicine.medical_specialty, business.industry, Chronic lymphocytic leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, Cyclophosphamide/Rituximab, Fludarabine, 03 medical and health sciences, Leukemia, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Rituximab, Online Only Articles, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience
Published: 2018
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38. Long-term follow up of the CLL2007FMP trial evaluating fludarabine and cyclophosphamide in combination with either rituximab or alemtuzumab in previously untreated patients with chronic lymphocytic leukemia

Author: Pierre Feugier, Damien Roos-Weil, Alain Delmer, Florence Nguyen-Khac, Beatrice Mahe, Rémi Letestu, Bruno Cazin, Florence Cymbalista, Marie C. Béné, Olivier Tournilhac, Bernadette Corront, Sandrine Vaudaux, Roselyne Delepine, Stéphane Leprêtre, Véronique Leblond, Bruno Royer, Olivier Casasnovas, Hervé Maisonneuve, Sylvie Chevret, Thérèse Aurran, Eric Van Den Neste, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, and UCL - (SLuc) Service d'hématologie
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Cyclophosphamide, Long term follow up, Chronic lymphocytic leukemia, Treatment outcome, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Online Only Articles, ComputingMilieux_MISCELLANEOUS, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Fludarabine, Leukemia, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, Alemtuzumab, Rituximab, business, Vidarabine, medicine.drug
Abstract: In fit chronic lymphocytic leukemia (CLL) patients without chromosome 17p deletion (del(17p)) or TP53 mutation, six cycles of FCR (fludarabine, cyclophosphamide, rituximab) provides the best progression-free survival (PFS) and overall survival (OS).1,2 In 2007, the French Innovative Leukemia Organization (FILO) group initiated the CLLFMP2007 study, a phase III trial in which fit patients with previously untreated CLL were randomized to six cycles of FCR or FCCam (fludarabine, cyclophosphamide, and alemtuzumab 30 mg subcutaneously on days 1-3 every 28 days). At the time, alemtuzumab, a humanized anti-CD52 monoclonal antibody, was one of the most active for treating CLL.3 Recruitment onto the CLLFMP2007 study was prematurely stopped because of excess toxicity in the FCCam arm, including 8 deaths, 4 from lymphoma and 4 from infection, in this cohort of 165 patients. We reported the initial results in 2012 with a median follow up of 38 months.4 Here, we provide the up-dated results with a median follow up of 76.4 months with particular attention to long-term outcome, toxicity, and minimal residual disease (MRD) data. [...]
Published: 2018
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39. A Meta-Analysis of Outcomes After In Situ Reconstructions for Aortic Graft Infection

Author: Michel Batt, Matthieu Revest, Frederic Laurent, Christian Chidiac, Amandine Coffy, Jocelyne Caillon, Jean Pierre Daures, Brigitte Calvet, Patrick Feugier, Eric Senneville, Fabrice Camou, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Unité de Chirurgie Vasculaire, CHU Lyon, Hôpital Saint-André, Département des Maladies Infectieuses [CH Tourcoing] (Hôpital Gustave Dron), Centre Hospitalier de Tourcoing-Centre Hospitalier Gustave Dron [Tourcoing], Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CH Béziers, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Gustave Dron [Tourcoing]-Centre Hospitalier de Tourcoing, Centre International de Recherche en Infectiologie (CIRI), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Reoperation, medicine.medical_specialty, Prosthesis-Related Infections, reconstruction, [SDV]Life Sciences [q-bio], Treatment outcome, 030204 cardiovascular system & hematology, Prosthesis Design, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Blood vessel prosthesis, Humans, Medicine, Prosthesis design, 030212 general & internal medicine, Prosthesis-Related Infection, Aortic graft, business.industry, in situ, infection, Blood Vessel Prosthesis, 3. Good health, Surgery, Treatment Outcome, surgical procedures, operative, graft, cardiovascular system, Cardiology and Cardiovascular Medicine, business, aortic
Abstract: Objective: To confirm the advantage of in situ reconstruction (ISR) over extra-anatomic reconstruction (EAR) for aortic graft infection and determine the most appropriate conduit including autogenous veins, cryopreserved allografts, and synthetic prosthesis (standard, rifampicin of silver polyesters). Methods: A meta-analysis was conducted with rate of mortality, graft occlusion, amputation, and reinfection. A meta-regression was performed with 4 factors: patients’ age, presence of prosthetic-duodenal fistula (PDF), virulent organisms, or nonvirulent organisms. Results: In situ reconstruction over EAR seems to favor all events. For the 5 conduits used for ISR, according to operative mortality, age of the patients looks to have a positive correlation only for silver polyester and no conduit present any advantage in the presence of PDF. Reinfection seems to be not significantly different for the 5 conduits, and only autogenous veins appear to have a positive correlation with infecting organisms. Conclusion: In situ reconstruction may be considered as first-line treatment. Our results suggest that silver polyesters appear to be most appropriate for older patients, and in order to limit reinfection, autogenous veins are probably the most suitable conduit.
Published: 2018
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40. Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study

Author: Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, Lymphoma Study Association (LYSA), Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Le Mans (CH Le Mans), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, 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), Service d'hématologie (CH de la Côte Basque), Le CHCB, Centre Hospitalier de la Côte Basque, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Léon Bérard [Lyon], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier de Bourg en Bresse, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
Subjects: Bendamustine, Male, medicine.medical_specialty, Efficacy, [SDV]Life Sciences [q-bio], efficacy, Follicular lymphoma, Phases of clinical research, Gastroenterology, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, rituximab, Maintenance therapy, follicular lymphoma, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, bendamustine, Lymphoma, Follicular, Aged, Aged, 80 and over, tolerance, business.industry, Remission Induction, Hematology, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Lymphoma, Tumor Burden, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Rituximab, Female, business, Tolerance, 030215 immunology, medicine.drug
Abstract: International audience; The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375mg/m intravenously combined with 2 cycles of bendamustine 90mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375mg/m rituximab maintenance therapy every 8weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12weeks. Median age was 67·4years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.
Published: 2018
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41. Eur J Cancer

Author: Carine Bellera, Catherine Thieblemont, Frédérique Rousseau, Sylvain Ladoire, Luc Thiberville, Mathilde Gisselbrecht, Jean Léon Lagrange, Merle Patrick, Hélène Nehme, Pascal Chaibi, Arnauld Villers, Erwan De Mones Del Pujol, Jean-Louis Bonnal, Pierre Feugier, Laeticia Stefani, Valérie Quipourt, Emmanuelle Bourbouloux, Audrey Mailliez, Valérie Le Brun-Ly, K. Leffondre, P. Soubeyran, Virginie Leroy, Brigitte Maget, Simone Mathoulin-Pélissier, Claire Falandry, Ludmilla Ribiere, Alain Ravaud, Florence Woerth, Nicolas Jovenin, Aurélien Minard, Matthieu Debray, Laurent Balardy, Matthieu Frasca, Gaelle Jeannin, Sandrine Lavau-Denes, Elisabeth Carola, Etienne Brain, Christian Gisselbrecht, Christian Rose, Serge Bologna, Laure de Decker, Olivier Rigal, Brigitte Comte, Muriel Rainfray, Philippe Caillet, Loic Mourey, Bordeaux population health (BPH), and 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)
Subjects: Male, Cancer Research, medicine.medical_specialty, Population, Comorbidity, Biostatistics, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Neoplasms, Internal medicine, Humans, Medicine, 030212 general & internal medicine, 10. No inequality, education, Geriatric Assessment, Aged, Aged, 80 and over, 2. Zero hunger, education.field_of_study, business.industry, Proportional hazards model, Mortality rate, Hazard ratio, Cancer, Geriatric assessment, EPICENE, Prognosis, medicine.disease, 3. Good health, Oncology, CIC1401, 030220 oncology & carcinogenesis, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Risk of death, business
Abstract: Introduction A comprehensive geriatric assessment (CGA) evaluating several domains of health is recommended for elderly patients with cancer. Effects of altered domains on the risk of death in this population need to be clarified. The aim of this study was to estimate the independent association of each CGA domain to overall survival (OS). Method Patients included in the ONCODAGE cohort completed a CGA at baseline. Cox models (one per domain) estimated the hazard ratio (HR) of death for each CGA domain. Directed Acyclic Graphs (DAGs) selected specific sets of adjustment factors for each model. Results The analysis included 1264 patients (mean age: 78 years, women: 70%). Median follow-up was 5.2 years, and 446 patients died. Each altered domain had a detrimental effect on survival, sometimes dependent on gender, age, education or time from inclusion. Nutritional status had a time-varying effect, with higher mortality rates if altered only within the first 3 years of follow-up. In case of altered mobility, the risk of death was higher only for the youngest patients and, in case of altered autonomy, only for the youngest women. An altered neurological state led to higher mortality rates; this effect increased with the level of education. Patients with altered psychological status or more than four comorbidities at baseline had also higher mortality rates. Conclusions Patients with an altered CGA domain have a higher risk of death than those without any alteration. The effect of some alterations is different in some subgroups or at a given time of the treatments.
Published: 2018
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42. First-line therapy for chronic lymphocytic leukemia in patients older than 79 years is feasible and achieves good results: A FILO retrospective study

Author: Meunier, Godelieve, Ysebaert, Loic, Nguyen-Thi, Phi Linh, Leprêtre, Stéphane, Quinquenel, Anne, Dupuis, Jehan, Lemal, Richard, Aurran, Thérèse, Tomowiak, Cécile, Cymbalista, Florence, Dilhuydy, Marie Sarah, Brion, Annie, Morel, Pierre, Cazin, Bruno, Leblond, Véronique, Cartron, Guillaume, Ré, Daniel, Bene, Marie Christine, Michallet, Anne Sophie, Feugier, Pierre, 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), 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), Service d'Hématologie Clinique [CHU Reims], Hôpital universitaire Robert Debré [Reims], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Adaptateurs de signalisation en hématologie (ASIH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service des maladies du sang, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Immunologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)
Subjects: [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017
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43. Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma

Author: Steven, Le Gouill, Catherine, Thieblemont, Lucie, Oberic, Anne, Moreau, Krimo, Bouabdallah, Caroline, Dartigeas, Gandhi, Damaj, Thomas, Gastinne, Vincent, Ribrag, Pierre, Feugier, Olivier, Casasnovas, Hacène, Zerazhi, Corinne, Haioun, Hervé, Maisonneuve, Roch, Houot, Fabrice, Jardin, Eric, Van Den Neste, Olivier, Tournilhac, Katell, Le Dû, Franck, Morschhauser, Guillaume, Cartron, Luc-Matthieu, Fornecker, Danielle, Canioni, Mary, Callanan, Marie C, Béné, Gilles, Salles, Hervé, Tilly, Thierry, Lamy, Remy, Gressin, Olivier, Hermine, Marie-Helène, Delfau-Larue, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire 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), 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), Institut de Mathématiques de Jussieu (IMJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, CHU Pontchaillou [Rennes], 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), Cliniques Universitaires Saint-Luc [Bruxelles], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Clinique Victor Hugo [Le Mans], Biophysique, Médecine Nucléaire et Technologies Médicales (EA 1049), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), CHU Strasbourg, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U823, équipe 7 (Voies Oncogéniques Des Hémopathies Malignes), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, croissance et cancer (U 1069) ( N2C ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Tours, CHU Caen, Université Paris-Sud - Paris 11 ( UP11 ), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy ( IGR ), 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 ), University Hospital of Nancy, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service de Médecine Onco-hématologie [La Roche sur Yon], Centre Hospitalier Universitaire de Nantes, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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 ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne ( CHELTER ), Université Clermont Auvergne ( UCA ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Institut Pluridisciplinaire Hubert Curien ( IPHC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Adaptateurs de signalisation en hématologie ( ASIH ), Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, and Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Randomization, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Lymphoma, Mantle-Cell, Hematopoietic stem cell transplantation, Transplantation, Autologous, Dexamethasone, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Maintenance therapy, Antineoplastic Combined Chemotherapy Protocols, Humans, Immunologic Factors, Medicine, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, ComputingMilieux_MISCELLANEOUS, Aged, Proportional Hazards Models, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, General Medicine, Middle Aged, medicine.disease, Combined Modality Therapy, Survival Analysis, 3. Good health, Lymphoma, Surgery, Transplantation, 030220 oncology & carcinogenesis, Female, Mantle cell lymphoma, Rituximab, Cisplatin, business, 030215 immunology, medicine.drug
Abstract: Mantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response.In a phase 3 trial involving 299 patients who were younger than 66 years of age at diagnosis, we randomly assigned 240 patients to receive rituximab maintenance therapy or to undergo observation after autologous stem-cell transplantation (120 patients per group); 59 patients did not undergo randomization. The primary end point was event-free survival (with an event defined as disease progression, relapse, death, allergy to rituximab, or severe infection) after transplantation among patients who underwent randomization.After four courses of immunochemotherapy induction (rituximab, dexamethasone, cytarabine, and a platinum derivative [R-DHAP]), the overall response rate was 89%, and the complete response rate 77%. Transplantation was performed in 257 patients. The median follow-up from randomization after transplantation was 50.2 months (range, 46.4 to 54.2). Starting from randomization, the rate of event-free survival at 4 years was 79% (95% confidence interval [CI], 70 to 86) in the rituximab group versus 61% (95% CI, 51 to 70) in the observation group (P=0.001). The rate of progression-free survival at 4 years was 83% (95% CI, 73 to 88) in the rituximab group versus 64% (95% CI, 55 to 73) in the observation group (P0.001). The rate of overall survival was 89% (95% CI, 81 to 94) in the rituximab group versus 80% (95% CI, 72 to 88) in the observation group (P=0.04). According to a Cox regression unadjusted analysis, the rate of overall survival at 4 years was higher in the rituximab group than in the observation group (hazard ratio for death, 0.50; 95% CI, 0.26 to 0.99; P=0.04).Rituximab maintenance therapy after transplantation prolonged event-free survival, progression-free survival, and overall survival among patients with mantle-cell lymphoma who were younger than 66 years of age at diagnosis. (Funded by Roche and Amgen; LyMa ClinicalTrials.gov number, NCT00921414 .).
Published: 2017
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44. Real-world results of ibrutinib in relapsed/refractory CLL in France: Early results on a large series of 428 patients

Author: Ysebaert, Loic, Aurran-Schleinitz, Thérèse, Dartigeas, Caroline, Dilhuydy, Marie-Sarah, Feugier, Pierre, Michallet, Anne-Sophie, Tournilhac, Olivier, Dupuis, Jehan, Sinet, Pierre, Albrecht, Claire, Cymbalista, Florence, 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), Département d'Hématologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Hospices Civils de Lyon (HCL), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Adaptateurs de signalisation en hématologie (ASIH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), 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), 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: [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017
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45. Ibrutinib in very elderly patients with relapsed/refractory chronic lymphocytic leukemia: A real-world experience of 71 patients treated in France: A study from the French Innovative Leukemia Organization (FILO) group

Author: Luc-Matthieu Fornecker, Fabien Subtil, Véronique Leblond, Loic Ysebaert, David Ghez, Anne-Sophie Michallet, Arnaud Campidelli, Jehan Dupuis, Helene Lequeu, Florence Cymbalista, Pierre Feugier, Olivier Tournilhac, Jean-Pierre Vilque, Sophie de Guibert, Alain Delmer, Marie-Sarah Dilhuydy, Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Strasbourg, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biostatistiques santé, 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), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and 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)
Subjects: Male, medicine.medical_specialty, Gastrointestinal Diseases, Chronic lymphocytic leukemia, Antineoplastic Agents, 030204 cardiovascular system & hematology, Infections, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Internal medicine, medicine, Humans, Molecular Targeted Therapy, Intensive care medicine, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Salvage Therapy, Dose-Response Relationship, Drug, business.industry, Adenine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Hematologic Diseases, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Leukemia, Pyrimidines, Treatment Outcome, chemistry, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Ibrutinib, Relapsed refractory, Pyrazoles, Female, France, business
Abstract: International audience
Published: 2017
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46. Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study

Author: Tout , Mira, Casasnovas , Olivier, Meignan , Michel, Lamy , Thierry, Morschhauser , Franck, Salles , Gilles, Gyan , Emmanuel, Haioun , Corinne, Mercier , Mélanie, Feugier , Pierre, Boussetta , Sami, Paintaud , Gilles, Ternant , David, Cartron , Guillaume, Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Clinical Investigation Center - INSERM 1415, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'hématologie clinique, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité des hémopathies lymphoïdes [CHU Henri Mondor], CHU Henri Mondor, 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), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), The European Lymphoma Institute, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA)-EA 7365 ( GRITA ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine ( UPEC Médecine ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Angers, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Hospices Civils de Lyon ( HCL ), CHRU Tours, Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Dynamique des interactions membranaires normales et pathologiques ( DIMNP ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Henri Mondor [Créteil], université de Bourgogne, LNC, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, immune system diseases, hemic and lymphatic diseases, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: IF 13.164; International audience; High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV0) on rituximab PK and of TMTV0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV0 was measured by (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m(2) rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV0 increased (R(2) = 0.41, P < .0001). A high AUC in cycle 1 (≥9400 mg × h per liter) was associated with better response (odds ratio, 5.56; P = .0006) and longer PFS (hazard ratio [HR], 0.38; P = .011) and OS (HR, 0.17; P = .001). A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV0 was constructed, and the 375 mg/m(2) classical dose would be suitable for patients with TMTV0
Published: 2017
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47. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial

Author: Gilles Salles, Martin Figeac, Hervé Tilly, B. Fabiani, Josette Brière, Danielle Canioni, M. Parrens, Marc André, R. Delarue, Jean-Philippe Jais, C Thieblemont, Christiane Copie-Bergman, Karen Leroy, Corinne Haioun, P. Feugier, Philippe Ruminy, Fabrice Jardin, Tony Petrella, Thierry Jo Molina, P. Gaulard, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), 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), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, 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), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'études spatiales de la biosphère (CESBIO), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche 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'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CHU Bordeaux [Bordeaux]
Subjects: 0301 basic medicine, Oncology, Male, Pathology, [SDV]Life Sciences [q-bio], Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Hazard ratio, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Treatment Outcome, Proto-Oncogene Proteins c-bcl-2, Vincristine, 030220 oncology & carcinogenesis, Prednisolone, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, medicine.medical_specialty, Disease-Free Survival, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Humans, Progression-free survival, Cyclophosphamide, Aged, business.industry, medicine.disease, Lymphoma, 030104 developmental biology, Doxorubicin, Prednisone, business, Diffuse large B-cell lymphoma
Abstract: Background Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. Patients and methods We evaluated 285 paraffin-embedded samples from patients (60–80years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. Results The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). Conclusions Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. Clinical trial Number NCT00144755
Published: 2017
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48. Popliteal Artery Entrapment Syndrome in Children: Experience With Four Cases of Acute Ischaemia and Review of the Literature

Author: Zakariyae Bouziane, Maarit Venermo, Nicla Settembre, P. Feugier, V. Nabokov, Michel A. Bartoli, Sergueï Malikov, Service de Chirurgie vasculaire (Hôpital de la Timone adultes), and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Myotomy, Male, Acute limb ischaemia, medicine.medical_specialty, animal structures, Adolescent, medicine.medical_treatment, Ischemia, Disease, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030204 cardiovascular system & hematology, 03 medical and health sciences, Peripheral Arterial Disease, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.artery, medicine, Humans, Popliteal Artery, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Paediatric patients, business.industry, Popliteal artery entrapment syndrome, medicine.disease, Popliteal artery, 3. Good health, Surgery, Treatment Outcome, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Claudication, business, Vascular Surgical Procedures
Abstract: Objective Popliteal artery entrapment syndrome (PAES) is an uncommon anatomical anomaly, frequently described in adults. The most common symptom is claudication. Acute limb ischaemia (ALI) in children is rare, but it may evolve and lead to limb loss or lifelong complications. Clinical and surgical experience of PAES in children is reported. Data from the literature are analysed in order to assess the severity of this disease and to identify the factors characterising the diagnosis and the outcome of treatment in paediatric patients. Methods Four children (aged 7–16 years) were referred with ALI due to PAES. Among the 439 articles reporting cases of PAES, 55 patients under 18 years of age were the focus. The PAES cases were classified according to the Love and Whelan classification modified by Rich. Results Data from 79 children (106 limbs, 27 bilateral PAES) were collected and analysed. Type I PAES was present in 41 (39%), Type II in 23 (22%), Type III in 24 (23%), Type IV in 12 (11%), and Type V in two (2%) limbs. A functional PAES was present in one patient bilaterally. In two cases, the type of PAES was not reported. Claudication occurred in 68 cases (64%), and ALI in 19 (18%). In 60 cases (57%), revascularisation with or without myotomy was required; myotomy alone was performed in 41 cases (39%). Conclusions Symptomatic PAES in children should be considered a severe condition requiring urgent investigation in order to avoid any delays in the treatment. Early diagnosis and treatment are essential to prevent serious complications. The long-term outcomes of surgical treatment with the correction of the anatomical anomaly and vascular reconstruction are satisfactory with a low complication rate.
Published: 2017
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49. Reproductive performance and pre-weaning mortality: Preliminary analysis of 27,221 purebred female dogs and 204,537 puppies in France

Author: Hanna Mila, Aurélien Grellet, Alexandre Feugier, Claire Mariani, Sylvie Chastant-Maillard, C Guillemot, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, NeoCare, Ecole Nationale Vétérinaire de Toulouse (ENVT), and Royal Canin
Subjects: Litter (animal), Male, Aging, Litter Size, 040301 veterinary sciences, [SDV]Life Sciences [q-bio], Weaning, Breeding, 0403 veterinary science, Endocrinology, Animal science, Dogs, Species Specificity, Puppy, Pregnancy, Reference Values, biology.animal, medicine, Animals, Body Size, Dog Diseases, reproductive and urinary physiology, biology, Mortality rate, Reproduction, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Abortion, Veterinary, Stillbirth, medicine.disease, 040201 dairy & animal science, Breed, Pregnancy rate, Multivariate Analysis, Animal Science and Zoology, Female, France, Seasons, Purebred, Biotechnology
Abstract: The objective of this study was to describe efficiency of reproduction of purebred dogs in field breeding conditions, from mating to weaning in France. Data were collected between 2010 and 2014 in 5,667 French breeding kennels via a reproduction management software (Breeding Management System, Royal Canin, Aimargues, France). Effect of breed size (Mini: adult body weight 40 kg), age of dam and male on pregnancy rate, abortion rate and litter size were evaluated by multivariable models. Data on 45,913 heats (all with mating), from 27,221 bitches from 248 breeds, were analysed. At mating, mean age (±SD) was 3.1 ± 1.8 years for bitches and 3.3 ± 2.0 for males. Males originated from the same kennel as the females in 88.5% of the matings. Based on breeder's evaluation of the pregnancy status, pregnancy rate (number of pregnant females based on breeders declaration/number of heats) was 87.8% and abortion rate was 6.8%. Finally, 81.9% of the mated females gave birth to a litter. On 37,946 litters (204,537 puppies), mean litter size was 5.4 ± 2.8 puppies (range 1-24), which was influenced by breed size and dam age (p
Published: 2017
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50. Natural and artificial hyperimmune solutions: Impact on health in puppies

Author: Sylvie Chastant-Maillard, Jörg M. Steiner, Alexandre Feugier, Blake C. Guard, Aurélien Grellet, Claire Mariani, Hanna Mila, Jan S. Suchodolski, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Royal Canin, gastrointestinal laboratory, and Texas A&M University System
Subjects: Serum, Health Status, morbidity, 0403 veterinary science, Endocrinology, fluids and secretions, Puppy, Medicine, Dog Diseases, 2. Zero hunger, biology, puppy, [SDV.BA]Life Sciences [q-bio]/Animal biology, 04 agricultural and veterinary sciences, 3. Good health, Milk, [SDV.IMM]Life Sciences [q-bio]/Immunology, Animal Nutritional Physiological Phenomena, Female, Original Article, canine milk, Antibody, Biotechnology, hyperimmune solution, Milk intake, 040301 veterinary sciences, growth, Immunoglobulins, Heterologous, Infections, Dogs, Immunity, biology.animal, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Animals, Weaning, MILK INGESTION, Pregnancy, Parturition and Neonatology, passive immune transfer, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, business.industry, Colostrum, 0402 animal and dairy science, canine colostrum, 040201 dairy & animal science, Animals, Newborn, Dietary Supplements, Immunology, biology.protein, Cattle, Animal Science and Zoology, business
Abstract: Contents Colostrum and milk are complex mammary secretions providing the puppy with many nutritional and immunological factors, which play a crucial role for its correct development and survival. In the case of colostrum and/or milk intake deficiency, puppies are at increased risk of infectious diseases. This work reviews the various nutritional hyperimmune supplementations proposed to provide a passive immune protection and to positively impact puppies’ health. Some strategies rely on canine immunoglobulins: canine colostrum banking and canine serum/plasma supplementation. Others involve heterologous sources of antibodies and other immune factors: bovine colostrum or hyperimmune egg powder. Among the different solutions evaluated from birth to weaning, canine plasma and hyperimmune egg powder showed promising beneficial effect on puppies’ health. Canine plasma seems to positively impact not only growth (increased growth during the neonatal period), but also digestive health (higher species richness of intestinal microbiota) and the general health (tendency of lower morbidity). Puppies supplemented with hyperimmune egg powder presented increased neonatal growth and decreased risk of canine parvovirus infection. Nevertheless, natural canine maternal colostrum and milk ingestion remains the optimal guarantee for puppies’ health and survival, as a source of immunity, energy and growth factors.
Published: 2017
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