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1. Diagnostic value of baseline 18FDG PET/CT skeletal textural features in follicular lymphoma

Author: Julie Faudemer, Nicolas Aide, Anne-Claire Gac, Ghandi Damaj, Jean-Pierre Vilque, and Charline Lasnon
Subjects: Medicine, Science
Abstract: Abstract At present, 18F-fluorodesoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) cannot be used to omit a bone marrow biopsy (BMB) among initial staging procedures in follicular lymphoma (FL). The additional diagnostic value of skeletal textural features on baseline 18FDG-PET/CT in diffuse large B-cell lymphoma (DLBCL) patients has given promising results. The aim of this study is to evaluate the value of 18FDG-PET/CT radiomics for the diagnosis of bone marrow involvement (BMI) in FL patients. This retrospective bicentric study enrolled newly diagnosed FL patients addressed for baseline 18FDG PET/CT. For visual assessment, examinations were considered positive in cases of obvious bone focal uptakes. For textural analysis, the skeleton volumes of interest (VOIs) were automatically extracted from segmented CT images and analysed using LifeX software. BMB and visual assessment were taken as the gold standard: BMB −/PET − patients were considered as bone-NEGATIVE patients, whereas BMB +/PET −, BMB −/PET + and BMB +/PET + patients were considered bone-POSITIVE patients. A LASSO regression algorithm was used to select features of interest and to build a prediction model. Sixty-six consecutive patients were included: 36 bone-NEGATIVE (54.5%) and 30 bone-POSITIVE (45.5%). The LASSO regression found variance_GLCM, correlation_GLCM, joint entropy_GLCM and busyness_NGLDM to have nonzero regression coefficients. Based on ROC analysis, a cut-off equal to − 0.190 was found to be optimal for the diagnosis of BMI using PET pred.score. The corresponding sensitivity, specificity, PPV and NPV values were equal to 70.0%, 83.3%, 77.8% and 76.9%, respectively. When comparing the ROC AUCs with using BMB alone, visual PET assessment or PET pred.score, a significant difference was found between BMB versus visual PET assessments (p = 0.010) but not between BMB and PET pred.score assessments (p = 0.097). Skeleton texture analysis is worth exploring to improve the performance of 18FDG-PET/CT for the diagnosis of BMI at baseline in FL patients.
Published: 2021
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2. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial

Author: Philippe Rodon, Cyrille Hulin, Brigitte Pegourie, Mourad Tiab, Bruno Anglaret, Lotfi Benboubker, Henry Jardel, Olivier Decaux, Brigitte Kolb, Murielle Roussel, Laurent Garderet, Xavier Leleu, Olivier Fitoussi, Carine Chaleteix, Philippe Casassus, Pascal Lenain, Bruno Royer, Anne Banos, Riad Benramdane, Pascale Cony-Makhoul, Mamoun Dib, Jean Fontan, Anne-Marie Stoppa, Catherine Traullé, Jean-Pierre Vilque, Marie-Odile Pétillon, Claire Mathiot, Thomas Dejoie, Hervé Avet-Loiseau, and Philippe Moreau
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2015
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3. The importance of harmonizing interim positron emission tomography in non-Hodgkin lymphoma: focus on the Deauville criteria

Author: Elske Quak, Narinée Hovhannisyan, Charline Lasnon, Christophe Fruchart, Jean-Pierre Vilque, Dada Musafiri, and Nicolas Aide
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2014
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4. A fixed-duration, immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial

Author: Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Lydia Campos, Michel Ticchioni, Marie-Sarah Dilhuydy, Stephane MORISSET, Valerie Rouille, Beatrice Mahe, Kamel Laribi, Bruno Villemagne, Emmanuelle France Ferrant, Olivier Tournilhac, Alain Jacques Delmer, Lysiane Molina, Veronique Leblond, Cécile TOMOWIAK, Sophie De Guibert, Frederique Orsini Piocelle, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc-Matthieu Fornecker, Loïc Ysebaert, Caroline Dartigeas, Malgorzata Truchan-Graczyk, Jean-Pierre Vilque, Thérèse Aurran Schleinitz, Florence Cymbalista, Stéphane Leprêtre, Vincent Lévy, Florence Nguyen-Khac, and Pierre Feugier
Subjects: Hematology
Abstract: In previously untreated, medically fit patients with chronic lymphocytic leukemia, research is focused on developing fixed-duration strategies to improve long-term outcomes whilst sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach where, following obinutuzumab-ibrutinib induction for 9 months, patients (n=10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD)
Published: 2023
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5. A Fixed-Duration Immunochemotherapy Approach Combined with Ibrutinib in CLL Produces Deep and Sustained MRD Responses: 5.5-Year Results from the Icll-07 Filo Trial

Author: Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Carmen Aanaei, Michel Ticchioni, Marie-Sarah Dilhuydy, Stephane Morisset, Valérie Rouille, Béatrice Mahé, Kamel Laribi, Bruno Villemagne, Emmanuelle Ferrant, Olivier Tournilhac, Alain Delmer, Christelle Portois, Lysiane Molina, Véronique Leblond, Cécile Tomowiak, Sophie de Guibert, Frederique Orsini, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc Mathieu Fornecker, Loic Ysebaert, Caroline Dartigeas, Margot Truchan, Jean-Pierre Vilque, Therese Aurran Schleinitz, Cymbalista Florence, Stéphane Leprêtre, Vincent Lévy, Florence Nguyen Khac, and Pierre Feugier
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022
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6. End-of-treatment 18F-FDG PET/CT in diffuse large B cell lymphoma patients: ΔSUV outperforms Deauville score

Author: Nicolas Aide, François Allioux, Damaj Gandhi, Jean-Pierre Vilque, Charline Lasnon, Cathy Nganoa, and Anne-Claire Gac
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Scoring system, Proportional hazards model, business.industry, Hematology, medicine.disease, Independent predictor, Regression, Response assessment, Internal medicine, Risk stratification, medicine, Fdg pet ct, business, Diffuse large B-cell lymphoma
Abstract: In DLBCL, the Deauville scoring system (DS) is the standard for PET/CT response assessment. An alternative system, based on the semi-quantitative change in standardized uptake values, namely ΔSUVmax, has been reported to be more objective than the DS. We aimed to compare ΔSUVmax and DS for risk stratification of DLBCL patients on end-of-treatment (EoT) PET. 108 consecutive patients were included. 2-year EFS Kaplan-Meier survival analyses and Cox regression models were performed. 2-year EFS was significantly different between favorable ΔSUVmax (favΔ < -86.5%) and unfavorable ΔSUVmax (unfavΔ ≥ -86.5%) patients: 100.0% ± 0.0 versus 58.3% ± 14.2 (p = 0.001). On Cox multivariable regression, ΔSUVmax status was the only independent predictor of 2-year EFS, outperforming DS. Therefore, ΔSUVmax should be computed for non-responder patients, especially DS4, as the 2-year EFS is not different between responders and non-responders in the case of favΔ. Further studies are needed in order to confirm this hypothesis.
Published: 2021
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7. End-of-treatment

Author: François, Allioux, Damaj, Gandhi, Jean-Pierre, Vilque, Cathy, Nganoa, Anne-Claire, Gac, Nicolas, Aide, and Charline, Lasnon
Subjects: Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Humans, Lymphoma, Large B-Cell, Diffuse, Prognosis, Retrospective Studies
Abstract: In DLBCL, the Deauville scoring system (DS) is the standard for PET/CT response assessment. An alternative system, based on the semi-quantitative change in standardized uptake values, namely ΔSUVmax, has been reported to be more objective than the DS. We aimed to compare ΔSUVmax and DS for risk stratification of DLBCL patients on end-of-treatment (EoT) PET. 108 consecutive patients were included. 2-year EFS Kaplan-Meier survival analyses and Cox regression models were performed. 2-year EFS was significantly different between favorable ΔSUVmax (favΔ-86.5%) and unfavorable ΔSUVmax (unfavΔ ≥ -86.5%) patients: 100.0% ± 0.0 versus 58.3% ± 14.2 (
Published: 2021

8. Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

Author: Jennifer Cautela, Paul Milliez, Stéphane Ederhy, Jean-Pierre Vilque, Ariel Cohen, Ghandi Damaj, Camille Ropert, Damien Legallois, Javid Moslehi, Christian Funck-Brentano, Charles Dolladille, Joachim Alexandre, Marion Sassier, Laure Champ-Rigot, Anne-Flore Plane, Franck Thuny, Joe-Elie Salem, Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Paris Est, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Département de Pharmacologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de cardiologie et de pathologie vasculaire [CHU Caen], Hôpital Nord [CHU - APHM], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie cellulaire des régulations hormonale, nutritionnelles et pharmacologiques (UMR-S-530), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Cardiologie [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), Laboratoire d'Hématologie Biologique [CHU Caen], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: pharmacovigilance database, [SDV]Life Sciences [q-bio], Antineoplastic Agents, 030204 cardiovascular system & hematology, World Health Organization, computer.software_genre, Pharmacovigilance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, medicine, Adverse Drug Reaction Reporting Systems, Humans, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Midostaurin, Lenalidomide, Database, business.industry, Ponatinib, Pomalidomide, Atrial fibrillation, United States, 3. Good health, Clinical trial, anticancer drugs, chemistry, Docetaxel, Cardiology and Cardiovascular Medicine, business, computer, medicine.drug
Abstract: Aims The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF. Methods and results A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody. Conclusion Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.
Published: 2020
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9. 18F-Fludarabine PET for Lymphoma Imaging: First-in-Humans Study on DLBCL and CLL Patients

Author: Jean-Pierre Pelage, Sylvain Chantepie, Alain Manrique, Anne-Claire Gac, Stéphane Guillouet, Méziane Ibazizène, Michel Leporrier, Thomas Carlier, Françoise Kraeber-Bodéré, Jean-Pierre Vilque, Gandhi Damaj, Louisa Barré, Caroline Bodet-Milin, Narinée Hovhannisyan, Emilie Reboursiere, 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, Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de l'élevage (IDELE), CHU Caen, Normandie Université (NU)-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), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Service de Médecine Nucléaire [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Biodistribution, Lymphoma, Chronic lymphocytic leukemia, Emission tomography, Molecular imaging, Physical examination, Effective dose (radiation), 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, First-in-humans, medicine, Radiology, Nuclear Medicine and imaging, Lymph node, medicine.diagnostic_test, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, 3. Good health, medicine.anatomical_structure, Positron emission tomography, 030220 oncology & carcinogenesis, Bone marrow, 18 F-fludarabine positron, Nuclear medicine, business
Abstract: CERVOXY/LDM-TEP COLL; International audience; This was the first-in-humans clinical study of 18F-fludarabine, which is a radiopharmaceutical for PET imaging in lymphoma, for which many issues remain controversial with the standard radiotracer 18F-FDG. Methods: 18F-fludarabine PET or PET/CT was performed on 10 patients: 5 with diffuse large B-cell lymphoma (DLBCL) and 5 with chronic lymphocytic leukemia. The tumor uptake, biodistribution, and radiation dosimetry of 18F-fludarabine were evaluated. Six successive partial-body PET scans were acquired for 250 min after an intravenous 4 MBq/kg bolus of 18F-fludarabine. SUVs were recorded for each involved lymph node territory and for several extranodal sites, with particular reference to the liver. To assess the time-related uptake profile of 18F-fludarabine, PET images were analyzed by delineating volumes of interest over the uptake sites on the optimal scan for visual observation and were projected onto all coregistered scans of the same subject. Physical examination, laboratory studies, and contrast-enhanced CT were performed on all patients. For the DLBCL group, 18F-FDG PET was also considered. Results: In DLBCL patients, increased 18F-fludarabine uptake was observed in sites considered abnormal by CT or 18F-FDG, with SUVs significantly higher in involved lesions than in physiologic nontarget sites. Nonetheless, the comparison of 18F-fludarabine and 18F-FDG PET showed discrepancies in 2 patients. In chronic lymphocytic leukemia patients, the uptake of 18F-fludarabine coincided with sites expected to be involved (including splenic invasion) according to conventional clinical and CT staging and was significant in hematopoietic bone marrow. No uptake was observed, whatever the disease group, in cardiac muscle or brain. The mean effective dose from a mean injected 18F-fludarabine activity of 305 ± 76 MBq was 3.07 ± 0.81 mSv. Conclusion: 18F-fludarabine PET might well be a promising tool for lymphoproliferative diseases. The radiation dose of this radiopharmaceutical is below that of 18F-FDG. The specificity of this PET probe for lymphoid cells, its absence of accumulation in reactive tissues, and its feasibility for detection of bone marrow infiltration might play an innovative role in lymphoma imaging.
Published: 2018
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10. Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study

Author: Sophie de Guibert, Thérèse Aurran-Schleinitz, Marie C. Béné, Hervé Maisonneuve, Anne-Sophie Michallet, Marie-Sarah Dilhuydy, Christian Berthou, Florence Cymbalista, Olivier Tournilhac, Stéphane Leprêtre, Eric Van Den Neste, Philippe Rodon, Kamel Laribi, Véronique Leblond, Florence Nguyen-Khac, Rémi Letestu, Pierre Feugier, Caroline Dartigeas, Jean-Pierre Vilque, Alain Delmer, Philippe Colombat, Julie Léger, Beatrice Mahe, Vincent Levy, Roselyne Delepine, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, 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 [Hôtel Dieu, Nantes], Hôtel-Dieu de Nantes, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), 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), 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 [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigations Cliniques 9504, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), 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)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service d'Hématologie clinique [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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, medicine.medical_specialty, Population, Phases of clinical research, Neutropenia, 03 medical and health sciences, 0302 clinical medicine, Chemoimmunotherapy, Internal medicine, Clinical endpoint, Humans, Medicine, education, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, 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, 030220 oncology & carcinogenesis, Female, Rituximab, Immunotherapy, business, Progressive disease, 030215 immunology, medicine.drug
Abstract: Summary Background Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus observation for elderly patients in remission after front-line abbreviated induction by fludarabine, cyclophosphamide, and rituximab (FCR). Methods This randomised, open-label, multicentre phase 3 trial at 89 centres in France enrolled treatment-naive and fit patients aged 65 years or older with chronic lymphocytic leukaemia without del(17p). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0–1 and adequate renal and hepatic function. Patients in response to complete induction treatment with four monthly courses of full-dose FCR with two interim rituximab doses on day 14 of cycles 1 and 2 (oral fludarabine [40 mg/m 2 per day] and oral cyclophosphamide [250 mg/m 2 per day] for the first 3 days of each cycle, rituximab at 375 mg/m 2 intravenously on day 0 of cycle 1 and subsequently at 500 mg/m 2 on day 14 of cycle 1, days 1 and 14 of cycle 2, and day 1 of cycles 3 and 4) were eligible for randomisation. Recovery from FCR toxicity and patient willingness to continue the trial were mandatory. We randomly assigned (1:1) patients to either receive intravenous rituximab (500 mg/m 2 ) every 8 weeks for up to 2 years or undergo observation, with a central computer-generated randomisation list using randomly permuted blocks of variable sizes. Randomisation was stratified by IGHV mutational status, the presence or absence of del(11q), and response level to induction treatment. The primary endpoint was progression-free survival, with the objective to assess the superiority of rituximab maintenance relative to observation. The final analysis was done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug in the rituximab group and in all patients in the observation group. This trial is closed to accrual whilst continuing patient follow-up. The study is registered with ClinicalTrials.gov, number NCT00645606. Findings Between Dec 14, 2007, and Feb 18, 2014, 542 patients were enrolled, of whom 525 started FCR induction. Between June 10, 2008, and Aug 14, 2014, 409 (78%) patients were randomly assigned to rituximab maintenance (n=202) or observation (n=207). Four (2%) patients in the rituximab group did not receive the allocated treatment (progressive disease [n=1], adverse events [n=3]). After a median follow-up of 47·7 months (IQR 30·4–65·8), median progression-free survival in the rituximab group (59·3 months, 95% CI 49·6–not estimable) was improved compared with the observation group (49·0 months, 39·9–60·5; hazard ratio 0·55, 95% CI 0·40–0·75; p=0·0002). Neutropenia and grade 3–4 infections were more common with rituximab maintenance (105 [53%] of 198 patients vs 74 [36%] of 207 patients and 38 [19%] vs 21 [10%], respectively) during the study. The most common grade 3–4 infection was lower respiratory tract infection (24 [12%] vs eight [4%]). The incidence of second cancers, except basal cell carcinoma, was similar in both groups (29 [15%] vs 23 [11%]). Deaths were related to adverse events for 23 (11%) patients in the rituximab group and 16 (8%) in the observation group. Interpretation 2-year maintenance rituximab in selected elderly patients improves progression-free survival and shows an acceptable safety profile. Immunotherapy maintenance strategy is a relevant option in front-line treatment of chronic lymphocytic leukaemia, even in the age of targeted therapy. Funding French National Cancer Institute (INCa), Roche, Chugai.
Published: 2018
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11. Single-Unit Transfusion Is Non Inferior to Double Unit Transfusion in Patients with Hematological Disorders Receiving Allogeneic or Autologous Bone Marrow Transplant or Induction Chemotherapy for Acute Leukemia: The 1versus2 Prospective Multicentric Randomized Clinical Trial

Author: Véronique Abonnet, Anaïs R Briant, Pascal Turlure, Jean-Baptiste Mear, Delphine Lebon, Jean-Jacques Dutheil, Yannick Chene, Amandine Charbonnier, Agnès Bazin, Anne-Claire Gac, Laure Peyro Saint Paul, Pascal Lenain, Stéphane Cheze, Jean-Pierre Marolleau, Jean-Pierre Vilque, Stephane Girault, Sylvain Chantepie, Oumedaly Reman, Jean-Jacques Parienti, and Fabrice Jardin
Subjects: Hematological disorders, medicine.medical_specialty, Acute leukemia, business.industry, Immunology, Induction chemotherapy, Cell Biology, Hematology, Autologous bone, Biochemistry, Surgery, law.invention, Bone transplantation, Randomized controlled trial, law, medicine, In patient, business
Abstract: Introduction Anemia is a common complication of hematological chemotherapy for acute leukemia and following hematopoietic stem cell transplantation (HSCT). Exposure to allogeneic blood transfusions has been associated with unfavorable outcome in several studies in a non-surgical settings. Retrospective studies in hematological intensive unit have suggested that single red blood cell (RBC) unit transfusion policy may reduce the number of RBC used in comparison with a classical double RBC unit transfusion policy, without clinical impact. The aim of the study was to demonstrate that single RBC transfusion was non inferior to the standard double RBC transfusion arm in terms of severe complication or mortality for inpatient with hematological malignancies. Key secondary endpoint, was the comparison of the numbers of RBC units transfused in each arm. Method In a phase 3 multicenter randomized trial, 245 adults' patients with acute leukemia requiring intensive chemotherapy or patients receiving autologous or allogeneic HSCT were randomly assigned (1:1) to receive either single RBC unit (1 RBC arm, n=125) per transfusion or double RBC (2 RBC arm, n=120) per transfusion when hemoglobin level was below 8g/dL. The primary composite endpoint was the percentage of patients who developed a grade ≥3 complications defined as stroke, transient ischemic attack, acute coronary syndrome, heart failure, elevated troponin level, intensive care unit transfer, death, new pulmonary infiltrates, and/or transfusion-related infections during hospital stays. The secondary endpoint was the number of red cell units transfused per patient per hospital stay. The primary endpoint was compared between groups by non-inferiority analysis for the proportion risk difference using Farrington-Manning method with a non-inferiority margin of 0.1, in ITT dataset. Results Hematological disease were as followed: AML (59%), ALL (13.1%), Lymphoma (16.4%), others (11.5%). The median age was 55 years. Baseline characteristics were well balanced between the 2 arms (Figure 1A). A total of 981 and 592 transfusions have been necessary in the 1 RBC arm and 2 RBC arm, respectively. The median of RBC unit per transfusion was 1(1-1) and 2(2-2) in the 1 RBC and 2 RBC arm, respectively. The mean pre transfusion hemoglobin level was 7.49 +/- 0.83 g/dL in the 1 RBC arm and 7.46 +/- 0.67 g/dL in the 2 RBC arm (p=0.275). Hemoglobin level at discharge was 9.35 +/-1.14 g/dL in the 1 RBC arm and 9.58 +/-1.13 g/dL in the 2 RBC arm (p=0.118). The median (IQR) of red-cell units transfused per patient was 7 (4-12) in the single arm and 8 (4-12) in the double arm (p=0.65). The median number of platelet transfusion event was 7 (3.5-11.5) in the 1 RBC arm and 7 (3-13) in the 2 RBC arm (p=0.69). The median (IQR) number of red cell unit transfused per cycle and per day was 7 (3-9) and 0.28 (0.17-0.37) in the 1RBC arm and 6 (4-10) and 0.27 (0.20-0.38) in the 2 RBC arm (p=0.61 and p=0.47). The predefined non-inferiority criteria was achieved with 28 patients developing a serious complication in the 1 CGR arm (22.4%) and 28 patients in the 2 RBC arm (23.3%) (Risk difference 0.009; 95% Confidence interval [-0.0791- 0.0978] (Figure 1B). Conclusion: Single RBC transfusion policy is non inferior to double RBC transfusion policy in hematological intensive care unit for patient receiving a bone marrow transplant or intensive chemotherapy. Single RBC unit transfusion can be used safely in daily clinical practice. The single RBC transfusion policy does not reduce the number of RBC transfusion. Figure 1 Figure 1. Disclosures Jardin: Genexpath: Patents & Royalties: The author is a potential inventor on a patent application for the LymphoSign, which has been licensed for by Genexpath Patents & Royalties. .
Published: 2021
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12. 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

13. Successful Imatinib therapy as a bridge to transplant in an atypical myeloproliferative neoplasm

Author: Sylvain Chantepie, Thomas Hueso, Alexandra Henry, Matthieu Decamp, Sarah Mensi, Hyacinthe Johnson-Ansah, Elsa Maitre, Gandhi Damaj, Jean-Pierre Vilque, Université de Caen Normandie (UNICAEN), Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Génétique [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Reims Champagne-Ardenne (URCA), Institut d'Hématologie de Basse-Normandie (IHBN), 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), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER
Subjects: Oncology, Bridge to transplant, medicine.medical_specialty, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Imatinib therapy, medicine.disease, General Biochemistry, Genetics and Molecular Biology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, Myeloproliferative neoplasm, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: International audience; No abstract available
Published: 2019
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14. Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial

Author: Carmen Aanei, Florence Nguyen-Khac, Luc Mathieu Fornecker, Marie-Sarah Dilhuydy, Anne Banos, Olivier Tournilhac, Stéphane Leprêtre, Anne-Sophie Michallet, Loic Ysebaert, Thérèse Aurran, Christelle Portois, Jean Pierre Vilque, Cécile Tomowiak, Veronique Leblond, Caroline Dartigeas, Pierre Feugier, Guillaume Cartron, Philippe Carassou, Rémi Letestu, Bruno Villemagne, Gilles Salles, Florence Cymbalista, Fabien Subtil, Vincent Levy, Kamel Laribi, Beatrice Mahe, Malgorzata Truchan Graczyk, Alain Delmer, Frederique Orsini, Brigitte Pegourie, Magali Le Garff-Tavernier, Michel Ticchioni, Sophie de Guibert, Valérie Rouille, 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: Male, medicine.medical_specialty, Neoplasm, Residual, Cyclophosphamide, Gastrointestinal Diseases, Population, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Obinutuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, Intention-to-treat analysis, Performance status, business.industry, Adenine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, Thrombocytopenia, 3. Good health, Fludarabine, Survival Rate, Pyrimidines, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Ibrutinib, Mutation, Pyrazoles, Female, Tumor Suppressor Protein p53, business, Immunoglobulin Heavy Chains, 030215 immunology, medicine.drug
Abstract: In patients with chronic lymphocytic leukaemia, achievement of a complete response with minimal residual disease of less than 0·01% (ie,1 chronic lymphocytic leukaemia cell per 10 000 leukocytes) in bone marrow has been associated with improved progression-free survival. We aimed to explore the activity of induction therapy for 9 months with obinutuzumab and ibrutinib, followed up with a minimal residual disease-driven therapeutic strategy for 6 additional months, in previously untreated patients.We did a single-arm, phase 2 trial in 27 university hospitals, general hospitals, and specialist cancer centres in France. Eligible patients were at least 18 years old and previously untreated, and had immunophenotypically confirmed B-cell chronic lymphocytic leukaemia; an Eastern Cooperative Oncology Group (ECOG) performance status score of less than 2; a Binet stage C according to IWCLL 2008 criteria or Binet stage A and B with active disease; no 17p deletion or absence of p53 mutation; and were considered medically fit. In the first part of the study (induction phase), all participants received eight intravenous infusions of obinutuzumab 1000 mg over six 4-weekly cycles and oral ibrutinib 420 mg once per day for 9 months. In part 2, after assessment on day 1 of month 9, patients with a complete response and bone marrow minimal residual disease of less than 0·01% received only oral ibrutinib 420 mg once per day for 6 additional months. Patients with a partial response, or with a complete response and bone marrow minimal residual disease of 0·01% or more, received 6 months of four 4-weekly cycles of intravenous fludarabine, cyclophosphamide, and obinutuzumab 1000 mg, alongside continuing ibrutinib 420 mg once per day. The primary endpoint was the proportion of patients achieving a complete response with bone marrow minimal residual disease less than 0·01% on day 1 of month 16 assessed by intention to treat (ITT). This trial is registered with ClinicalTrials.gov (number NCT02666898) and is still open for follow-up.Between Oct 27, 2015, and May 16, 2017, 135 patients were enrolled. After induction treatment (day 1 of month 9), 130 patients were evaluable, of which ten (8%) achieved a complete response with bone marrow minimal residual disease of less than 0·01% and were assigned to ibrutinib, and 120 (92%) were assigned to ibrutinib plus fludarabine, cyclophosphamide, and obinutuzumab. After minimal residual disease-guided treatment (day 1 of month 16), 84 (62%, 90% CI 55-69) of 135 patients (ITT population) achieved a complete response with bone marrow minimal residual disease of less than 0·01%. The most common haematological adverse event was thrombocytopenia (in 45 [34%] of 133 patients at grade 1-2 in months 1-9 and in 43 [33%] of 130 patients at grade 1-2 in months 9-15). The most common non-haematological adverse events were infusion-related reactions (in 83 [62%] patients at grade 1-2 in months 1-9) and gastrointestinal disorders (in 62 [48%] patients at grades 1 and 2 in months 9-15). 49 serious adverse events occurred, most frequently infections (ten), cardiac events (eight), and haematological events (eight). No treatment-related deaths occurred.Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease driven strategy is safe and active in patients with previously untreated chronic lymphocytic leukaemia. With longer follow-up, including assessing the evolution of minimal residual disease, if response is maintained, this strategy could be an option in the first-line setting in patients with chronic lymphocytic leukaemia, although randomised evidence is needed.Roche, Janssen.
Published: 2019
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15. The prognostic value of hematogones in patients with acute myeloid leukemia

Author: Anne-Claire Gac, Véronique Salaun, Gandhi Damaj, Khaled Benabed, Jean-Pierre Vilque, Sylvain Chantepie, Oumedaly Reman, Jean-Jacques Parienti, Margaret Macro, Hyacinthe Johnson-Ansah, and Stéphane Cheze
Subjects: Oncology, medicine.medical_specialty, Myeloid, Performance status, business.industry, Induction chemotherapy, Myeloid leukemia, Hematology, medicine.disease, Minimal residual disease, 03 medical and health sciences, Leukemia, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, Immunology, medicine, Bone marrow, business, Survival analysis, 030215 immunology
Abstract: In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse-free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 - 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 - 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk-adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566-570, 2016. © 2016 Wiley Periodicals, Inc.
Published: 2016
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16. 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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17. Bendamustine-based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers

Author: Roch Houot, Charles Herbaux, Rene-Olivier Casasnovas, Thomas Gastinne, Frederic Peyrade, Diane Coso, Remy Gressin, Emilie Reboursiere, Krimo Bouabdallah, Gandhi Damaj, Marie-Virginie Larcher, Luc-Mathieu Fornecker, Momar Diouf, Mohamed Amine Bekadja, Jean-Pierre Vilque, Ahmad Ibrahim, Sandra Malak, Sylvain Garciaz, Sylvain Chantepie, Eric Durot, Anne-Claire Gac, Stéphanie Guidez, Caroline Delette, Ibrahim Yakoub-Agha, Carole Soussain, Emmanuelle Tchernonog, Richard Lemal, 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: Bendamustine, medicine.medical_specialty, Carmustine, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Gastroenterology, 3. Good health, Transplantation, 03 medical and health sciences, Regimen, 0302 clinical medicine, Autologous stem-cell transplantation, 030220 oncology & carcinogenesis, Internal medicine, medicine, Mucositis, business, Etoposide, ComputingMilieux_MISCELLANEOUS, 030215 immunology, Pneumonitis, medicine.drug
Abstract: Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m2 /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m2 and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.
Published: 2018
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18. Increased frequencies of circulating and tumor-resident Vδ1 T cells in patients with diffuse large B-cell lymphoma

Author: Kathy Khoy, Khaled Benabed, Christophe Fruchart, Anne-Dominique Pham, Anne-Claire Gac, Oumedaly Reman, Véronique Salaun, Emilie Reboursiere, Sylvain Chantepie, Jean-Baptiste Mear, Stéphane Cheze, Margaret Macro, Xavier Troussard, Olivier Toutirais, Gandhi Damaj, Quentin Cabrera, Jean-Pierre Vilque, Hyacinthe Johnson-Ansah, Anthony Garnier, Brigitte Le Mauff, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), and Université de Rouen Normandie (UNIROUEN)
Subjects: 0301 basic medicine, Cancer Research, T cell, diffuse large B-cell lymphoma, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, medicine, Cytotoxic T cell, CD40, biology, CD28, Germinal center, Hematology, Natural killer T cell, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, cancer immunosurveillance, Oncology, Gamma-delta T cells, Immunology, biology.protein, Interleukin 12, immunotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1+ T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1+ T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1+ T cells of patients or HSs mostly exhibited a naive phenotype, the majority of tumor Vδ1+ T cells showed a central memory phenotype. Resident or circulating γδ T cells from patients were not functionally impaired since they produced high levels of IFN-γ. Collectively, our findings are in favor of γδ T cell activation in tumors and open new perspectives for their modulation in DLBCL immunotherapy.
Published: 2018
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19. Gemtuzumab ozogamicin in combination with intensive chemotherapy in relapsed or refractory acute myeloid leukemia

Author: Sylvain Chantepie, Margaret Macro, Emilie Reboursiere, Jean-Baptiste Mear, Stéphane Cheze, Oumedaly Reman, Khaled Benabed, Véronique Salaun, Jean-Pierre Vilque, Hyacinthe Johnson-Ansah, and Anne-Claire Gac
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Gemtuzumab ozogamicin, Salvage therapy, Antibodies, Monoclonal, Humanized, Gastroenterology, Young Adult, European LeukemiaNet, Refractory, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Salvage Therapy, Response rate (survey), business.industry, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Prognosis, Gemtuzumab, Survival Analysis, Confidence interval, Surgery, Leukemia, Myeloid, Acute, Aminoglycosides, Treatment Outcome, Oncology, Toxicity, Female, business, medicine.drug
Abstract: The prognosis of refractory/relapsed acute myeloid leukemia (AML) remains poor. The complete response (CR) rate after relapse is around 25%, with 11% of patients still alive after 5 years. The efficacy and toxicity of fractionated gemtuzumab ozogamicin (fGO; 3 mg/m2, days 1, 4, 7) in combination with intensive chemotherapy were retrospectively evaluated in patients with refractory/relapsed AML. Thirty-six patients (median age 54 years) were included. European LeukemiaNet classification was as follows: favorable (n=6), intermediate-I (n=13), intermediate-II (n=8), adverse (n=9). Median CR duration was 7.16 months (1.63-96.8). The overall response rate was 38.8%, with CR in eight patients (22.2%) and CR with incomplete platelet recovery (CRp) in six patients (16.7%). Two-year overall survival was 26% (95% confidence interval [CI]: 12-42) and 2-year relapse free-survival was 18.5% (95% CI: 6.6-35.0). Salvage therapy with fractionated GO in patients with very high-risk disease produced a 38.8% response rate and may be considered as a bridge therapy to transplant.
Published: 2015
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20. Increased frequencies of circulating and tumor-resident Vδ1

Author: Emilie, Reboursiere, Anne-Claire, Gac, Anthony, Garnier, Véronique, Salaun, Oumedaly, Reman, Anne-Dominique, Pham, Quentin, Cabrera, Kathy, Khoy, Jean-Pierre, Vilque, Christophe, Fruchart, Sylvain, Chantepie, Hyacinthe, Johnson-Ansah, Margaret, Macro, Stéphane, Cheze, Khaled, Benabed, Jean-Baptiste, Mear, Xavier, Troussard, Gandhi, Damaj, Brigitte, Le Mauff, and Olivier, Toutirais
Subjects: Adult, Aged, 80 and over, Male, Receptors, Antigen, T-Cell, gamma-delta, Middle Aged, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating, T-Lymphocyte Subsets, Cytokines, Humans, Female, Immunotherapy, Lymphocyte Count, Lymphoma, Large B-Cell, Diffuse, Immunologic Memory, Immunologic Surveillance, Aged, Neoplasm Staging
Abstract: Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1
Published: 2017

21. 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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22. Results From a Prospective, Open-Label, Phase II Trial of Bendamustine in Refractory or Relapsed T-Cell Lymphomas: The BENTLY Trial

Author: Arnaud Jaccard, Momar Diouf, Gandhi Damaj, Thierry Lamy, Pascale Cony-Makhoul, Krimo Bouabdallah, Bertrand Joly, Roch Houot, Guillaume Cartron, Steven Le Gouill, Emmanuel Gyan, Remy Gressin, Jean-Pierre Vilque, Bachra Choufi, Marie-Christine Béné, Sophie Park, Michael Bubenheim, Laurence Sanhes, Aline Schmidt-Tanguy, Laurent Voillat, Jean-Marc Schiano-de Collela, Anne Banos, Alain Saad, Olivier Tournilhac, Jean-Pierre Marolleau, Antoine Martin, CHU Amiens-Picardie, 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), CHU Bordeaux [Bordeaux], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Duchenne, CH Boulogne sur Mer, CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Bayonne, Centre Hospitalier de la Côte Basque (CHCB), CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital Sud-Fancilien, CH Sud-Fancilien, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital de Béziers, CH Béziers, Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de Perpignan, Centre Hospitalier Saint Jean de Perpignan, CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Avicenne [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), CH de la Côte Basque, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Le Corre, Morgane
Subjects: Male, MESH: Remission Induction, Cancer Research, medicine.medical_treatment, Salvage therapy, MESH: Antineoplastic Agents, Alkylating, Gastroenterology, MESH: Aged, 80 and over, 0302 clinical medicine, Bendamustine Hydrochloride, Prospective Studies, Aged, 80 and over, MESH: Aged, education.field_of_study, MESH: Middle Aged, Remission Induction, MESH: Neoplasm Staging, MESH: Follow-Up Studies, Middle Aged, MESH: Lymphoma, T-Cell, Peripheral, Prognosis, MESH: Drug Resistance, Neoplasm, MESH: Lymphoma, T-Cell, Cutaneous, Lymphoma, T-Cell, Cutaneous, MESH: Salvage Therapy, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Nitrogen Mustard Compounds, Female, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, Bendamustine, medicine.medical_specialty, MESH: Survival Rate, Population, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Neutropenia, MESH: Prognosis, 03 medical and health sciences, Refractory, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, Antineoplastic Agents, Alkylating, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Survival rate, Aged, Neoplasm Staging, Salvage Therapy, Chemotherapy, MESH: Humans, business.industry, MESH: Nitrogen Mustard Compounds, Lymphoma, T-Cell, Peripheral, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Lymphoma, Surgery, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, business, MESH: Female, Follow-Up Studies, 030215 immunology
Abstract: Purpose To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas. Patients and Methods Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m2 per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results Of the 60 patients included, 27 (45%) were refractory to their last prior chemotherapy, and the median duration of the best previous response was 6.6 months. Histology was predominantly angioimmunoblastic lymphadenopathy and PTCL not otherwise specified. The disease was disseminated in the majority of patients (87%). The median number of previous lines of chemotherapy was one (range, one to three). Twenty patients (33%) received fewer than three cycles of bendamustine, mostly because of disease progression. In the intent-to-treat population, the ORR was 50%, including complete response in 17 patients (28%) and partial response in 13 patients (22%). Bendamustine showed consistent efficacy independent of major disease characteristics. The median values for DoR, PFS, and OS were 3.5, 3.6, and 6.2 months, respectively. The most frequent grade 3 to 4 adverse events were neutropenia (30%), thrombocytopenia (24%), and infections (20%). Conclusion Bendamustine showed an encouraging high response rate across the two major PTCL subtypes, independent of age and prior treatment, with acceptable toxicity in refractory or relapsed T-cell lymphoma.
Published: 2013
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23. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Author: Odile Fremin-Batteux, Juliette Clarissou-Philippe, Benoît Jauhlac, Severine Guyetand, Jacques Gasnault, Corinne Haioun, Liamine Aissaoui, Marie-Christine Pages, Marie-Pierre Fos, Christian Rose, Didier Hubert, Marie-Rose Rothe, N. Bouziges, Benoît Huc, François Devianne, Sabine Bidart, Anne Forest, Kevin Bertrand, Mohamed Eldeghedy, Annick Verhaeghe, Caroline Malderet, Anne Bertrou, Bernard Guerquin, Catherine Duche, Muriel Archambaud, Rabea Cotteret, Olivier Toullalan, Yves Devaux, Smail Bergheul, Valérie Sivadon-Tardy, Pierre-Gilles Merville, Geneviève Blanchard-Marche, Didier Raoult, Bernard Hory, Florence Richardin, Evelyne Belle, Mohamed Menouar, K Guitteaud, Mohamad Mohty, Ambroise Montcriol, Max Laurin, Aurélia Picard, Jean-Paul Mira, Marie-Charlotte Chopin, Richard Bonnet, Michel Wolff, Sébastien Maillez, Jeanne Maugein, Véronique Leblond, Nicola Walid, Bernard Gauche, Mathieu Evillard, Hassen Jeddi, Anne Bourlet, Isabelle Grawey, Thierry Jault, Sandrine Hiret, Valerie Gaborieau, Véronique Boin-Gay, An Kim, Thierry Constans, Jean-François Gaide, Martine Giraud, Eric Meaudre Desgouttes, Alain Fur, Abdallah Maakaroun, Olivier Matray, Bertrand Maubert, Frédérique Péchinot, Aurelie Garbi, Claire Delbrouck, Benoît Grandclerc, Vincent Cadiergue, Hervé Lécuyer, Bernadette Grignon, Thierry Bensaid, Nicole Constantin, Yannick Chevalier, Hassène Rahmani, Thierry Levent, Joelle Desliers, Florence Van de Velde, Xavier Adhoute, Clara Andriau, Christophe Charasse, Rémi Vatan, Benoît Martha, Alain Lecis, Didier Albert, Romain Jacobs, Hélène Lefranc, Christian Martin, Nasseur Rezgui, Bertrand Pigeon, Catherine Le Henaff, Dominique Cassignard, Françoise Cotes, Eric Pujade Lauraine, Jean-François Gattault, Nicole Ferreira-Maident, Noémie Jourde-Chiche, Hélène Garrec, Olivier Darchen, Carole Schwebel, Marie-Christine Bezian, Patrick Daoud, Tsouria Becaid, Simone Laluque, David Broche, Christine Boisselier, Pascale Martres, Sarah Hammami, Brigitte Olivier, Jean-Marie Nkunzimana, Eric Monlun, Isabelle Marterl-Lafay, Marion Carboni, Marie-Françoise Mattei, Sandrine Castelin, Isabelle Barillot, Marie-Noelle Cufi, Thomas Kaiser, Catherine Herry, Pascal Hutin, Jean-Pierre Bronowicki, Bernard Branger, Pierre Thomas, Elie Zagdoun, Anne Goquelin, Ziad Assaf, Ingrid Croquet, Bruno Pozzetto, Thomas Similowski, Anne-Isabelle Briere, Marie-Thérèse Albertini, Mariam Blaka, Christelle Tassot, Anne Gaschet, Jean-Philippe Lavigne, Antoine Pujol, Philippe Colombat, Edouard Devaud, Hana Talabani-Boizot, François Barière, Anne-Marie Cordier, Philippe Gueudet, Georges Simon, Anne-Sophie Lipovac, Françoise Bandaly, Anne Beauplet-Lepage, Sylvie Prince, Charlotte Jouzel, Jean-Luc Deboutin, Patrick Zavadil, Louis Puybasset, Marie-Cécile Petit, Loïc Guillevin, Kamel Touati, Christophe Ntalu Nkato, Sylvie Carette, Jacques Vaucel, Chantal Delasalle, Marine Gross Goupil, Laurent Gutmann, Christiane Payen, Annick Barboteau, Firouzé Bani-Sadr, Christophe Legendre, Philippe Roulier, Elie Azria, Ibrahim Farah, Isabelle Rouquette-Vincent, Anne-Sophie Erena-Penet, Philippe Labadie, Eric Josien, Aicha Derragui, Mathieu Legrand, Odile Beyne-Rauzy, Jean-Marc Nabholtz, Marie-Joelle Demarcq, Olivier Garosi, Michel Deiber, Fabrice Chaix, Bertrand Souweine, Anne Collignon, Gisèle Renard, Mickael Jego, Gilles Bernardin, Anne Allart, Jocelyn Barrier, Marc Vasse, Philippe Ménager, Marc Wurmser, Abderkader Ouazir, Olivier Gontieron, Yvon Berland, Sébastien Trouiller, David Leysenne, Christophe Ozanon, Fanny Autret, Tahar Saghi, Loïc Dopeux, Sophie Benoit-Coustou, T. Fraisse, Christine Maillard, Karine Nikodijevic, Georges Kaltenbach, Angéline Jamet, Philippe Aucher, Julie Bottero, Marie-Claude Piffaut, Marianne Besnard, Florence Courillon, Marie Bonfils, Christine Ghevaert, Marie Destors, Eliette Jeanmaire, Franck Zerbib, Manuel-Luis Gameiro, T Prazuck, Laurent Mandin, Olivier Guisset, Marguerite Fines, Toufik Feddal, Agnès Jouffret, Louis Mesnard, Thomas Bourrée, Hasinrina Razafimahefa, Sylvestre Tigaud, Vincent Estève, Philippe Malherbe, Jean-Michel Salord, Pascal Adam, Bertrand Rozec, Michel Fuillet, Olivier Lemenand, Denis Quinsat, Ana Danalaché, Véronique Vialette, François Brosset, Patrick Messner Pellenc, Nicolas Heisel, Edouard Girard, Régine Martin, Olivier Garesslin, Catherine Mille, Alexandre Gascon, Marc Nicolino, Laurence Mouly, Claire Fabre, Bénédicte Ponceau, Marie-Etiennette Emeriau, Pascal Cathebras, Bérangère Bernardaud, Michèle Pérouse de Montclos, O. Arsene, Karine Grenet, Yazdan Yazdanpanah, Sten De Witte, Anne Scemla, Laurence Bouillet, Christophe Burucoa, Vincent Loffeier, Séverine Visentin, Luc Desfrere, Miloud Arabi, Frédérique Costa, Sylvie Lechat, Ali Chekroun, Raymond Ruimy, Marie, Jérôme Bizet, Xavier Nassif, Baihas Dib, Patrick Bert-Marcaz, Laurent Martin Lefèvre, Nicholas Sedillot, Blandine Cattier, Emilie Boidin, Daniel Sondag, Aude Bourrouillou, Alain Noirot, Franck Desemerie, Fréderic Heluwaert, Catherine Tamalet, Marc G. Berger, Jean-Daniel Lelièvre, Dominique Perotin, Abdelkader Bemrah, Alain Lozniewski, Bernard Borstein, Hanna Eid, Diana Suatean, Virginie Mignaut, Jean-Claude N'guyen, Valérie Le Goff, Laurent Teillet, Christophe Rolland, Gwenaël Alfonsi, Florence Lachenal, Philippe Bossi, Yves Botreau, Florence Doucet Populaire, Henry Jardel, Nicolas Gallo, Elias Jabre-Sikias, Michel Dupon, Hélène Brihier, Isabelle Patry, Alexandre Leclercq, Bernadette Tourrand, Christophe Roussel, Jean-Emmanuel Kurtz, Bénédicte Paindaveine, Simon Elhadad, Richard Sanchez, Eric Sgro, Pierre Berger, Valérie Murbach, Anne Holstein, Florence Martin, Taoufik Merabet, Amélie Benbara, Milagros Ferreyra, Laure Esposito, Pierre Delobel, Antoine Andremont, Marc Bourlière, Carole-Anne Boudy, Jean-Baptiste Gaulthier, Laurent Tacchini, Olivier Marpeau, Sonia Tesseydre, Marie-Pierre Coulhon, Nathalie Hodee, Marie-Chrsitine Conroy, Pierre Weinbreck, Roland Leclercq, Laurent Souply, Christian Bidault, Annie Elbez, Marie-Annick Lebreton, Patrick Brisou, Agnès Ferroni, Jean-Louis Pourriat, Nadia Anguel, Christian Noel, Philippe Jouvencel, Eric Pichard, Xavier Martin, Mathieu Coste, Pierre Zuber, Catherine Neuwirth, Jean-Pierre Hacot, Paul Aye, Jérôme Guinard, Yves Pean, Jean-Christophe Dengo, Fabrice Petassou, Didier Viole, Thierry Messiaen, Jean Beytout, Philippe Petitjean, Ferdinand Savare, Patrice Cuvillier, Sophie Coignard, Hélène Anglaret, Nassim Kamar, Elisabeth Chachaty, Karine Guimard, Louis Braem, Hacene Fezoui, Pierre Martin, Jean-Paul Viard, Claire Larroche, Nicolai Claudiu-Plesa, Thierry Benoit-Cattin, Olivier Moquet, Thierry Pasdeloup, David Rosay, Rodolphe Jean, Jean-Bernard Mariette, Marc Debouverie, Hervé Peltier, Mustapha Terki, Jacques Daleas, Valérie Dattin-Dorrière, Michel Vergnaud, Emmanuel Grimprel, Sylvène Rosselli, Jean-Marc Didier, Pierre Faurie, Luc Frimat, Aziza Mandjee, Sabine Etchemendy, Pierre Tissières, Jean Nakhleh, Sylvie Mariette, Christian Perronne, Bruno Carbonne, Nathalie Houssiaux-Maisonneuve, Tristan Ferry, S Beague, Anthony Sebban, Marie-Thérèse Hili, Jean-Michel De Kermadec, Lucien Brasme, Gilles Blaison, Caroline Garandeau, Jean-Pierre Sollet, Laurent Tronchon, Thierry Samson, Julien Gesquière, Nicolas Ettahar, Alain Créange, Etienne Laurens, Véronique Equy, Fréderic Bart, Bernard Bouffandeau, Christine Vaillant, Valerie Pesque, Jean-Marc Lalot, Marc Levy, Michel Kaidomar, Mihaela Saplacan, Sterenn Yvenou, Marie-Isabelle Steibach, Emmanuelle Cambau, Agnès Riche, François Fourrier, François Raffi, Mélissa Lalu, Henri Bérard, Danielle Clave, Jean-Claude Mouries, Martine Porcheron, Jean Cabalion, Richard Lamarca, Nathalie Canu, Jean-Baptiste Roseau, Annabelle Stoclin, Luca Luminitan Elena Lupean, Rémi Gebeile, Celia Salanoubat, Carole Marmouset, Pierre Bigot, Anne-Laure Breton, Pierre Kalfon, Colette Vincent, Sophie Marty, Olivier Tandonnet, Alexis Redor, Xavier Valette, Ourida Aoudia, Jacques-Arnaud Seyrig, Bertrand Beaune, Hugues Aumaitre, Georges Pinon, Yann Leveneur, Sylvie Charachon, Raoul Herbrecht, Henriette de Valk, Gary David, Julien Pouyanne, Marc Dommergues, Majed Al Chaar, Véronique Blanc-Amrane, Pascale Guillarmé Grossmann, Bruno Abraham, Yves Morel, Philippe Suel, Denis Sautereau, Olivier Guilloy, Tu Anh Tran, Frédéric Laurent, Zahir Amoura, Jacques-Olivier Bay, Zoubida Elharie-Heraux, Joyce Sibony-Prat, Bernard Guillois, Dominique Rohmer-Heitz, Audrey Barrelet, Jérémie Courouble, Jean-Paul Herry, Daniel Vittecoq, Annie Vermesch-Langlin, Jean Auroux, Claude Aubert, Thierry Harvey, Ghislaine Lamoine-Gimet, J. Riahi, Florence Soraudeau, Bachar Al-Jalaby, Caroline Périsson, Khélifa Ayouz, Florence Cardot, François Maillet, Alain Goux, Théophile Magna, Bertille de Barbeyrac, Adrien May, Dominique Andreotti, Olivier Jonquet, Hélène Dumouchel, Didier Thibaud, Philippe Morlat, Pascal Chevalet, Pascal Ancelin, Guy Chambreuil, Cécile Le Boterff, Anne Ceriez, Olivier Detante, B Pangon, Claude C.A. Bernard, Vincent Cailleaux Pierre-Etienne Cailleux, Jordi Miatello, Pierre-Yves le Berruyer, Sylvain Kouaho, Michel Briaud, Hélène Delaby, Patrick Herbecq, Christine Segonds, Véronique Jault, Pascale Brunel, Christine Dussopt, Jean Thore, Jean-Marc Thouret, Jean-Marc Kerleau, François Le Baron, Slavius Matica, Sophie Leautez-Nainville, Matthieu Pecquet, Laurent Bret, Yacine Sedjelmaci, Pierre Metton, Habiboulaye Diallo, Jany Rey Zermati, Arnaud Delahaye, Hélène Chaussade, Laurent Mandelbrot, Emilie Bessede, Olivier Casanovas, Paul Pierrot, Annick Legras, Dominique Lauque, Hélène Gatti, Jean Catineau, Ebutu Likose, Gilles Capellier, Eric Kibbrecht, Freddy Thibaut, Patrick Valadier, Chantal Lemble, Joël Gaudelus, Joelle Mellier, Joëlle Brochen, Emmanuel Gascou, Stéphane Bonacorsi, Stéphanie Bannier, Bruno Fantin, Didier Raffenot, Valérie Revel, Hakim Amroun, Huguette Negrery, Anne-Laure Fauchais, Paul Mercury, Michel Chuzeville, Christian Zumbo, Nicolas Després, Pascal Roblot, Jérôme Pasche, Jean Claude Boufetteau, Jocelyne Caillon, Julien Boileau, V. Rabier, Benjamin Manéglier, Emilie Jourdes, Franck Ceppa, Christine Recule, Nicolas Degand, Benoît Henry, Thierry Baranger, Dominique Pateron, Agnès Pélaquier, Gérard Bouchet, Hélène Fiette, Ozel Guiden, Dana Ranta, Etienne Ruppé, Nabil Chiouk, Jacques Breuil, Dominique Leduc, Véronique Loustaud, Hervé Métenier, Michel Durand, Isabelle Mahé, Leila Karaoui, Marie-José Collus, Mehran Monchi, Olivier Belmonte, Romain Blondet, Jacques Thierry, Karine Humbert, Gilles Salama, Marie-Noelle Heurtaux, Cécile Goujard, Bruno Sivery, Martial Boisseau, Redouane Dahoumane, Pierre Delour, Christian Niels Meyer, Anne Faudon-Gibelin, Gérard Poulain, Roger-Charles Luciani, J.-C. Souquet, Olivier Grossi, François Vandenesch, Sylvain Mermont, Jacques Bronner, Sonia Dahan, Paul Marzouk, Pascal Pouedras, Noureddine Djafari, François-Xavier Caroli-Bosc, Jean-François Dessin, Brigitte Gruffat, Armelle Morin-Fatome, Sylvie Thoinet, Bano Konate, Jean-Winoc Decousser, Claire Poyart, Patrick Plessis, Olivier Millet, Vincent Cattoir, Françoise Geffroy, Manica Vasseur, Pierre Carli, Isabelle Citony, Christian Richard, Nicolas Sigur, Patrick Marthelet, Luwawu Mbimba, Pierre Feugier, Philippe Sauder, Hama Djerad, Evelyne Bourgerette, Hanen Chahtour, Adrien Lemaignen, Dominique Bechade, Patrick Ochocki, Antoine Vieillard Baron, Dominique Astruc, Marie-Pierre Moiton, Nicolas Dubois, Sylvie Ledru, Corinne Seknazi, Hélène Poupet, Jean-Philippe Brieux, Gérard Barthélémy, Aihem Yehia, Louis-Jean Couderc, Ahmed, Françoise Rigaux, Yohann N'guyen, Philippe Bethery, Damien Corberand, Etienne Auvray, Paul-Louis Woerther, Christian Combe, Sophie Delesalle, Jean-Marie Piala, Faraj Al Freijat, Philippe Juvin, Malcolm Lemyze, Hyacine Rey, Claire Larible, Noel Milpied, Lémia Zgarni, Julia Gaillard, Agnès Juven, Paola Otean, Adrien Melis, André Pechinot, Olivier Bouchaud, Olivier Chassin, Pierre Hausfater, Asma Trabelsi-Jnifen, Vincent Grobost, Didier Lemery, Pierre Soury, Françoise Brevet, Jacques Tankovic, Dominique Sansot, Jean Louis Salomon, Charlotte Cordonnier, Brigitte Lamy, Antoine Maisonneuve, Dominique Pressac, Claude Rémy, Rodolphe Sobesky, Stéphanie Cognet, Pierre Cougoul, Didier Jan, Dominique Perrotin, Cécile Hombrouk-Alet, Thierry André, Gilbert Pochmalicki, Serge Girard, Vincent Zerr, Guillaume Cadiot, Claudine Lasbasses, Michel Slama, Abderrazak El Yamani, Sophie Brovedani, Jean Armengaud, Romain Hernu, Géraldine Mascade, Aurélien Lorléa'ch, Ali Akkari, Mathieu Tourdjman, Christopher Payan, Eric Jullian, Nathalie Fonsale, Frédéric Riehl, Paul Strock, Geneviève Grise, Philippe Mottaz, Christian Floriot, Marie-Noëlle Ungeheuer, Denis Caillot, Arnaud Chalvon-Demersay, Catherine Branger, Stanislas Bruley des Varannes, Marc Paccalin, Marie-Pierre Danjean, Alexandre Mebazaa, Xavier Brunet, Roland De Varax, Laurence Delhoustal, Sophie Haro, Bruno Chabanon-Pouget, Isabelle Goidin, Dominique Chudersky, Corinne Costes, Delphine Chatellier, Maud Gelez, Damien Dassant, Pascal Joly, Jean-Michel Arnal, Zakaria Hamitou, Philippe Rondepierre, Carole Pignon, Valérie Crombe, Amanda Lopes, Chrystelle Kemenar, Olivia Raulin, Anne-Cécile Hochart, Sandrine Gérart Pons, Valérie Zeller, Guillermo Reyes Ortega, Mathilde Guérin, Audrey Migraine Bouvagnet, Florence Eboue, Isabelle Loury-Lariviere, Sophie Leotard, Suzanne Lima, Marie Kassis, Jean-Luc Donay, Jean-Pierre Audié, Guillaume Cartron, Arnaud Ribier, Fanny Buron, Mirela Tuca, Marius Semenescu, Arnaud Serre, Vincent Quentin, Denise Bouyssou-Destriau, Violaine Bresson, Christine Chandesris Joséphine Chapalain-Cagnon, Eric Cua, Henri Courtade, François Bénézit, Sébastien Lamache, Philippe Bonnefoy, Francis Schneider, Richard Monarchi, Adeline Schendel, Paramasiven Mootien, Ghislaine Gardes, Pierre-François Westeel, Jean-François Magny, François Caron, Jocelyn Michon, Didier Eyer, Isabelle Ronda, Pierre-Yves Robillard, Frédéric Renou, Anna Faucher, Jean-Robert Harlé, Anne Debernardi, Grégory Akerman, Benoît Fontenel, Pierre Hourdebaigt-Larrusse, Marie-Noëlle Adam, Aude Lessene, Abdelkader Hrichi, François Blot, Athéna Le Pierres, Romain Lemarie, Françoise Granier, Véronique Tardy, Marc Gatfosse, Pierre-Marie Roger, François Goupil, Saïd Aberrane, Franck Bernardi, Isabelle Plantier, Nathalie Funakoshi, Jean-Gilles Delecalle, Patricia Barbut, Jacques Reynes, Christophe Roy, Sophie Perreve, Michel Garre, David Ribes, Cyrille Ede, Jean-Claude Dausset, Francis Duchene, Jean Caussin, Michelle Becker-Schneider, Gilles Berthelot, Damien Dupont, Jean-Michel Gillot, Aurélie Messager, Jean-Marie Pannecouck, Jean-Christian Roussel, Alain Reynaud, Sylvie Cariou, Anne Dao, François Guillemot, Martin Martinot, Patrick Casali, Anne-Sophie Poirier, Aissa Kerchache, Necera Sakek, Eric Porthault, Christophe Decoene, Chantal Ache-Papillon, Brigitte Bicais, Jean-Claude Feugier, Thierry Masseron, Charles Marty-Ane, Daniele Goldgran Toledano, Jean-Christophe Dubus, Damien du Cheyron, Dominique Decré, Jean-Loup Pennaforte, Ahmed Tigaizin, Bernard Vache, Eric Oswald, Claire Moulinoux, Anne-Christine Jaouen, Caroline Charlier, Anne-Laure Virlouvet, Ali Kara, Jean-Luc Sicsic, Sylvie Goffart, Mathieu Zuber, Claudine Fèbre, Olivier Lortholary, Mathieu Dupont, Annie Vessieres, Thierry Helvadjian, Thomas Signouret, Cedric Daupin, Sandrine Essouri, Jean-Louis Jacob, Pascal Boileau, Caroline Blazejewski, Quentin Lepiller, Juan-Pablo Maureira, Eddy Lebas, Christophe Deschamps, Amévi Ananivi, Clovis Foguem, Daniel Adoue, Abdourahim Chamouine, Alain Michault, Bruno Guérin, Olivier Baud, Clara Vinci, Thierry Weitten, Jean-Marc Eychene, Marie Froidure, Julien Obiols, Patricia Roussellier, Marc Lecuit, André Cabié, Saskia Foucart, Karim Belhadj, Michel Cingotti, Bruno Dumoulard, Jean Puyhardy, Etienne Danquechin Dorval, Lucile Mendes-Martin, Enrique Casalino, Luc Jarrige, Fabien Lambiotte, Philippe Masson, Mohammed Mansouria, Pierre Thouvenot, Katy Jeannot, Martine Nyunga, Valérie Macci, Florent Masia, Claire Briere de la Hosseraye, Wassila Anteur, André Sommabère, Marie-Claude Germain, Isabelle Arnault, Bernard Carbonelle, Philippe Devos, Daniel Protar, Tiphaine Gaillart, Ludovic Lassel, Laurence Hamou-Plotkine, David Trystram, Thierry Bureau, Olivier Collard, Fanny Vuotto, Sophie Malhiere, Frederique Canis, Gillles Plainfosse, Catherine Lechiche, Bertrand Lassere, Martine Chouraqui, Jean Baptiste Michot, Fethi Radhouane-Khanjari, Carole Barbier, Pascal Bonitchi, Abdelaziz Benkhelil, Odile Salmon, Laurent Damaj Gandhi, Bertrand Minguet, Michel Wagner, Odile Falguières, Zahr-Eddine Ali Chaouche, Eric Zaoui, Isabelle Guichard, Bernard Huttin, Apollinaire Karirisi, Gaël Cinquetti, Christophe Plane, Lionel Rostaing, Yanne Henry-Andrieu, Daniel Re, Virginie Verrier, Pascal Bolot, Michel De Biasi, Laurence Vrigneaud, Mathilde Turpin, Marie-Claude Demachy, Etienne Roussel, Michèle Blancs, Olivier Join-Lambert, Yves Ville, Thierry Granger, Gilles Hilbert, Virginie Medeau, Daniel Villers, Benoit Pilmis, François Gouraud, Emmanuel Ardiet, Catherine Heyraud-Blanchet, Alain Devidas, Hélène Dieye, Julie Cremniter, Jean-François Bergmann, Rozenn Le Berre, Virginie Leguen, Daniel Royer, Gilles Le Maout, Christian Harou, Sylvie Gabriel-Soléan, Yves Regouby, Martine Pestel-Caron, Patrick Brunet, David Boutoille, Emmanuelle Bonnin, Patrice Coulon, Marc Sullice, Marianne Barbieux, Gilles Cambonie, Joëlle Tricoire, Marie-Nadège Bachelier, Delphine Briend, Céline Ramanantsoa, Nathalie Bednarek, Didier Lebreton, Julien Lagrandeur, Damien M'Bey, Philippe Audeguy, Elie Saliba, Lena Damaj, Hassan Fallouh, Pascal Couturier, Fabrice Prévost, Yves Domart, Marie-Odile Lafforgue, Anne Le Du, C. Beuscart, Pierre Guillet, Fabrice Larrazet, Marie-Hélène Hausermann, Henri Robert, Nicolas Fanjaud, François Goehringer, Thomas Bachelot Philippe Badia, Jean-Michel Coulaud, Cristel Fissore Magdelein, Renaud Defebvre, Anne-Sohie Moreau, Johan Courjon, Gilles Salles, Michel Mialon, Silvia Iacobelli, Emmanuelle Bille, Marie-Christine Barbier, Yves Aubard, Patrice Badila, Jean-Philippe Rasigade, Alban Deroux, Evelyne Lecaillon-Thibon, Michel Godin, Abdelmajid Djeffal, Viorica Badurescu, Meriem Canitrot, Pierre Blanchard, Antoine Legros, Laurence Got, Françoise Duluc, Mylène M. Maury, Gilles Dassieu, Nordine Khodeir, Jean-Marie Duez, Mathieu Morincomme, Jérôme Lacroix, Mathieu Revest, Koffi Blewoussi, Isabelle Barazer, Françoise Poitevin, Camille Seignovert, Stéphanie Honore Bouakline, Anne Heidt, Brigitte Malbruny, Julien Desblache, Christian Cattoen, Eric Jaunait, Bruno Chaminade, Claude Bazin, Jonathan Chelly, Anne Pottier, Alain Schmitt, Alain Tissot, Karim Dadoun, P. Rebattu, Claudine Contamin, Arnaud Guerard, Nathalie Ravet, Sandrine Khalifa-Thellier, Marlène Chatron, Gaëlle Dörr, Hélène Biessy, Emmanuel Forestier, Bruno Devaux, Jean-Jacques Grelaud, Xavier Tchenio, Marie-Cécile Ploy, Jérémie Violette, Michèle Burdin, Lionel Falchero, Dominique Jacomy, Jean-Christophe Rozé, Damien Labarriere, Stéphane Leroux, Corinne Meregnani, Assia Ferhat Carre, Paul Orode, Jean-Gabriel Paul, Catherine Godon, Agnès Vinay, Régine Barraduc, Dominique Dallay, Alexandre Ampère, Anne-Gaelle Kervegant, Guillaume Louart, Dominique Beal Ardisson, Francoise Leonetti, Jean-Yves Baril, Stéphanie Haiat, Bincy Darre, Jérôme Bay, Yvan Gauthier, Sylvie Radenne, Pierre-Yves Gueugniaud, Philippe Ravaud, Luc Landraud, Guillaume Ranchon, Loïc Chimot, Véronique Duval, Ilhem Agha-Mir, Sabine Camiade, Estelle Wafo, Jean-Patrick Laporte, Mariam Roncato-Saberane, Camille Bron, Patrice Laudat, Samir Kennouche, Nawel Afroukh, Dominique Neri, Hakim Kherouf, Yoar Hichri, Pierre-Edouard Bollaert, Gwenaelle Vary, Denis Castaing, Christine Lefort, Sébastien Rouget, René Robert, Christelle Guillet-Caruba, Catherine Simonin, Alain Vighetto, Severine Cabasson, Alain Brusset, Alexandra Doloy, Christel Cherlet, Ahmed Rouidi, Marina Salvucci, Réginald Pordes, René-Gilles Patrigeon, Emmanuelle Dupre-Narlet, Jacques Minet, Fethi Taleb, Anne-Marie Colingorski, Tahar Hadou, Sylvain Diamantis, Isabelle Glorieux, Thierry May, Jean-Claude Colombani, Anne Berth-Farges, Nicole Desplaces, Renaud de Tayrac, Elisabeth Walter, Fabienne Lorge, Pascal Reboul, Nathalie Dournon, Laurence Estépa, Marie-Lina Toubia, Mathilde Flahault, Thierry Delacour, Dominique Hurel, Hélinoro Andriamaneo, Cécile Bébéar, Denis Grasset, Miloud Serier, Oléna Orléva, Nadine Dubroca, Hervé Gentilhomme, Jean-Luc Baudel, Isabelle Lavenu, Salim Smati, Carlo Saroufim, Eric Placidi, Albert Sotto, Benoît Libeau, Hélène Leroy, François Golfier, Christophe Dollon, Laurence Desnoulez, Eric Barre, Daniel Cohen, Pascal Priollet, Thierry Marsepoil, Benoît Lionnet, Jacques Tebib, Pascale Penn, Antoine Bouissou, Christian Roth, Olivier Martinet, Anna Schmitt, Nathalie Fruleux, Fouzia Radaoui, Jean-Marc Lessinger, Virginie Morando, Jean-Jacques Maillet, Christophe Fruchart, François Boué, François Goffinet, Franck Lellouche, Martin Demarchi, Alain Geissler, Jean-Charles Picaud, David Assouline, Patricia Brazille, Philippe Guimier, Marie-Françoise Dabysing, Bruno Delpeuch, Vanessa Tran, Guy Gengembre, Delphine Deligne, Dominique Vodovar, Yvan Touze, Sabrina Parent, Anne Decoster, Camille Dewitte, Emmanuel Weiss, Thierry Lambert, Thomas Guimard, Vincent Caille, Claude Guérin, Françoise Evreux, Geneviève Barjon, Basile Ondze, Damien Fournier, Olivia Bandin, Sophie Mignart, Henri Demontclos, Didier Perez, Jacques Croize, Nicole Desbois-Nogard, Guenièvre Imbert, Clarisse Dupin, Khalid Ridah, Marie-Christine Varin, Guillaume Arlet, Edith De Clareuil, Marie-Line Eustache, Patricia Le Pimpec, Louise Fortin, Eugène Ngami, Fabrice Mihout, Cecilia Esnault, Vincent Bouden, Véronique Annaix, Yves Poinsignon, Aurélien Lorchleac'h, Jean-Marc Degreff, Marie Garofano, Renaud Mesnage, Anne-Marie Roque-Afonso, Alain Chevailler, Stéphane Hominal, Thierry Charbonnier, Adrianna Bildea, Fabien Fily, Benjamin Davido, Emmanuel Rassiat, Assi Assi, Stéphanie Brunet, Hervé Jacquier, Catherine Claise, Annie Durand, Yannick Monceau, Pierre Blanc, Jean-Marie Sire, Yves Sucin, Jean-Pierre Zarski, Nathalie Bronet, Ingrid Lafon, Philippe Rey, Jacques Markarian, Eric Sennevile, Olivier Wink, Guilène Barnaud, Anne-Sophie Peultier, Sabine Taylor, Rim Savatier, Patrick Valayer, Claude Negrier, Selim Jennane, Edouard Begon, Laura Hyerle, Delphine Bridoux, Claire Daurel, Benoît Dalle, Mathilde Lescat, Philippe Stolidi, Elodie Perrodeau, Xavier Heches, Pierre Castelnau, Philippe Bray, Jean-Claude Texier, Serge Rossignol, Maud Brung-Lefebvre, Jean-François Subra, Jean-Marie Delarbre, Morgane Schneerson, Guyro Jang, Mona Mehri, Nathalie Landgraf, Pierre-Marie Girard, Armand Goll, Zaineb Bekguesmia, Christophe Clement, Michel Collet, Vincent Maze, Amine Benjelloul, Solène Durliat-Ellie, Vincent Letouzey, François Schmitt, Valérie Martinez, Sarah Watson, Abderrezak Bouasria, François Barbier, Raphael Lauretta, Mirana Razafimahery, Cristina Sirbu, Patrick Malherbe, Anne Wuillai, Ludovic Lesecq, Philippe Gaudard, Serge Houssaye, Jacques Monsegu, Gilles Rival, Chantal Chaplain, Jean-Didier Grangé, Oana Zamfiri, Florence Nguyen-Khac, Marc Portneuf, Jean-Michel Pawlotsky, Delphine Bonnet, Laurent Traissac, Sophie Hamon-Charles, Didier Dreyfuss, Louis Bernard, Laurence Detourmignies, Olivier Martineau, François Pettinelli, Marc Zandecki, Michel Dreyfus, Alain Chapelle, Sébastien Sabbat, Anne-Sophie Labussiere, Jean-Louis Gaillard, Chloé Plouzeau-Jayle, Patrick Zoveda, Véronique Leflon, Marie Levy, Aurélie Labé, Bruno Soulie, Raoul Jacques Bensaude, Hecham Moussa, Sylviane Catteu, Nathalie Biron, Loïc Masson, Georges Mourad, Nejla Aissa, Dragos Ciocan, Hubert De Boysson, Jean-Luc Bouyer, Patrick Yeni, Thierry-Pascal Zame, Caroline Thomas, François Cavalié, Laurence Koulmann, Christophe Rioux, Olivier Barraud, François Bricaire, Marguerite Le Poulain, Marie-Noelle Noulard, René Thomas, Guy Semet, Laurent Mosser, Olivier Marret, Brigitte Rivière, Vincent Jarlier, Jean-Philippe Coindre, Marc Villemain, Martin Pierre, Yacine Benkaci, Philippe Chiron, Hoang Vu-Thien, Jérôme Gournay, Andrea Labaune-Kiss, Brigitte Lauzanne, Fanny Lemercier, Souad Silhadi, Imad Kansau, Christophe Poncelet, Olivier Baldesi, Francis Thuet, Olivier Leroy, Aurore Lamberet, Camille Petit Hoang, Sophie Micheli, Ayman Abokasem, Hakima Nesrine, Pierre Lureau, Christian Chidiac, Vincent Piriou, Fabien Zoulim, Dieudonné Nicobaharaye, Anne Tixier, Isabelle Matheron, Soumeth Abasse, Victoria Cacheux, Serge Herson, Christine Fuhrmann, Olivier Proost, Bernard Bedock, Olivier Rogeaux, Mostapha Hajjar, Anne Reverseau, René Courcol, Françoise Carmagnol, Yves Guénard, Céline Ménard, Bouchra Lamia, Bruno Lemmens, Damien Bouhour, L. Lequen, Gaëlle Baty, Cédric Bouet, Dominique Guerrot, Stéphane Blanc, Catherine Chirouze, Anne-Hélène Reboux, A. Vachée, Gregory Taurin, Myriam Mein-Bottini, Jean-Pierre Belot, Alain Lafeuillade, Patricia Gabez-Therou, Philippe Labrousse, Bernard Jarrousse, Philippe Noto, Vincent Brunot, Philippe Condominas, Marion Challier, Béatrice Berçot, Delphine Anuset, Mélanie Daval Cote, François Bernasconi, Y. Costa, Chandrah Goburdhun, Bernard Gressier, Alban Michaud-herbst, Franck Charlier, Moussa Hecham, Luc Boulain, Hélène Corneloup, Alix Greder Belan, Nicolas Boussekey, Claire-Antoinette Dupuy, Yannick Rouquet, Benoit Renard, Benifla Jl, Etienne Javouhey, Michèle Granier, Marie-Christine Jaffarbandjee, Emilie Piet, Benoît Bergues, Claire Malbrunot, Catherine Tiry, Philippe Mérigot, Mouna Ben Soltana, Chantal Roure Sobas, Florian Radenac, Yves Thomas, Agathe Blaise, Sylvie De Martino, Laurence Legout, Gabriel Choukroun, Jean-François Muir, Peggy Dupretz, Patrick Dupont, François Guichart, Julie Jean, Jean-Michel Descamps, Bernard Kittschke, Anne Gruson, Gerard Viquesnel, Marie Keller, Pascal Chavanet, Françis Vallet, Yvan Vaschalde, Jean-Luc Hanouz, Gerard Lina, Françoise Loison, Simon Vincent, Jean-Paul Thellier, Moncef Afi, Dominique Zagozda, Hélène Sokeng-Affoule, Marc Le Bideau, Jean-François Loriferne, Alain Gravet, Sophie Deprecq, Tarik Naceur, Severine Mielczarek, René-Jean Bensadoun, Bernard Karkous, Yves Bléher, Jocelyne Poulain, Véronique Goulet, Laurence Nicolet, Sophie Arista, Antônio Lúcio Teixeira, Jean-François Schved, Laurent Nicolet, Claire Lecomte, Faiza Benddif-Fin, Michel Aumersier, Laurence Burc-Struxiano, Maxime Thouvenin, Samia Harbi, Mathieu Detave, Catherine Rebeyrotte, Jean-Paul Kisterman, Bruno Berdin, Pascal Vincent, Laurent Argaud, Elisabeth Parisi-Duchene, Geneviève Julienne, Fernanda Farto-Bensasson, Georges-Fabrice Blum, Sad Gaizi, Tali-Anne Szwebel, Raphaël Lepeule, Marie-Thérèse Climas, Anne-Françoise Dillies, Amar Boudhane, Umberto Simeoni, Pierre-François Dequin, Gérard Oliviero, Alain Gourlaouen, Caroline Piau, Marie-France Lutz-Murphy, Benoît Claude, Jean-Paul Aubry, Nadine Dubosc-Marchenay, Kamilla Chraibi, Emmanuelle Heusse, Sylvain Le Chevallier, Nathalie Brieu, Farid Sifaoui, Lorraine Letranchant, Hélène Durox, Jean-Pierre Lagasse, Adel Ghedira, Xavier Roubert, Fatma Magdoud, Hélène Jean-Pierre, Etienne Carbonelle, Olivier Dereeper, Lionel Carbillon, Christophe Billy, Mélanie Roblin, Marie-José Kodzin, Philippe Niel, Solène Makdessi, Matteo Vassallo, Maryse Archambaud, Fabian Haccourt, Didier Blaise, Stéphane Bourgeois, Elena Marcu, Charles Kubiak, Brisse Castel, François Guinet, Marie Pouzoullic, Frédérique Nathan-Bonnet, Vincent Gendrin, Céline Becherrawy, Aline Secher, Pierre Abgueguen, Clarence Eloy, Jean-Marc Tourani, Frédéric Klapczynski, Bernard Montmasson, Philippe Real, Joanna Pofelski, Yves Welker, Karim Krechiem, Eric Caumes, Martine Elena-Daumas, Christophe Saigne, Gilles Hittinger, Chantal Delesalle, Jonathan Messika, Fabrice Lesage, Daniela Pop, Daniel Coetmeur, Renato Colamarino, Chetaou Mahaza, Patrick Plésiat, Isabelle Fredenucci, Mylène Baret, Guy Mager, Pascale Chavel, Isabelle Labourdette, Anne-Claude Menguy, Nicolas Fortineau, Ludovic Le Sec, Valérie Gauduchon, Francis Barraud, Nicolas Letellier, Didier Vincent, Janine Frey, Philippe Riegel, Michel Pavic, Jean-Luc Fabre, Jean-Pierre Fauchart, Alain Goudeau, Stéphanie Husson-Wetzel, Philippe Eymerit, Mohamed Camara, Nathalie Seta, Elisabeth Carole Ngo Bell, Philippe Repellin, Laurent Alric, Vincent Leroy, Françoise Delisle Mizon, Jean-Philippe Emond, Marie-Françoise Borie, Lise Crémet, Wladimir Chelle, Elisabeth Brottier-Mancini, Bernard Garrigues, Claire Letellier, Loïc Geffray, Frédéric Méchaï, Julien Bador, Benoit Guery, Alain-Charles Fouilhoux, Corinne Dagada, Pierre Duhaut, Julien Goustille, Arnaud Sément, Francis Carcenac, Isabelle Girard-Buttaz, Claire Chapuzet, Fabienne Jouatte, Bruno Riou, Fabrice Hayoun, Chloé Di Meglio, Youssef Ali, Michel Leneveu, Nathalie Montagne, Yves Garcera, Audrey Moustache, Pierre-Eric Danin, Geneviève Le Lay, Dominique Courouge-Dorcier, Isabelle Worcel, Emmanuel Morelon, Vincent Pestre, Jean-Pierre Vilque, Jean-Christophe Paquet, Lucien Bodson, Anne-Marie Forest, Fabrice Pierre, Christian Pommier, Fabien Dutasta, Pierre Fournel, Stéphanie Courtois, Elodie Dubois, Serge Vanden Einjden, Patrick Honderlick, Pascal Richette, Fabienne Tamion, Véronique Chassy, Richard Megbemado, Anne-Marie Le Reste, Bernard Simian, Henri Osman, Anthony Texier, Badih Ayach, François Simon, Jean-Michel Filloux, Béatrice Dubourdieu, Jean-Claude Semet, Sarah Kubab, Tawfiq Henni, Patrick Dudeffant, Delphine Hequet, Olivier Mimoz, Marc Auburtin, Amélie Chabrol, Mickael Bonnan, Caroline Léonnet, Claire Wintenberger, Serge Ilunga, Patrice Lanba, Sophie Rosello, Alexandre Damage, Flore Bouche, Michel Thibault, Frederic Faibis, Chantal Dhennain, Jean-Philippe Talarmin, Armelle Lamour, Remi Boussier, Fabien Garnier, Marie-Laure Brival, Nourredine Hedjem, Philippe Vande-perre, Raphaël Coint, Jean-Claude Reveil, Eva Weinbronn, Emmanuelle Lavalard, Alexandra Fille, Françoise Le Turdu, Lionel Leroux, Jean-Yves Lefrant, Jean Berthet, Radia Bouaziz, Alain Ravaud, Sylvaine Rousseau, Yacine Merrouche, Alain Le Coustumier, Bertrand Guider, Gisèle Dewulf, Jean-Marc Faucheux, Jacques Piquet, Franck Leibinger, Charles Cerf, Robin Stephan, Jean-Philippe Redonnet, Jean-Paul Stahl, Ella Dzeing, Simona Pavel, Guy Vernet, Ghada Hatem, Samer Kayal, Jacques Deschamps, Dominique Descamps, Marion Levast, Marc Bouiller, Sylvie Dargere, Claire Dingremont, Stéphane Gaudry, François Maillot, Sylvie Odent, Nathalie Cervantes, Hélène Zanaldi, Laurence Gachassin, Olivier Ruyer, David Patin, Benoît Cazenave, Pascal Jacquier, Michelle Boyer, Béatrice Berteaux, Virginie Zarrouk, Jacques Bor, Isabelle Legoff, Hélène Albinet, Florence Rousseau, Gilles Pialoux, Guenaelle Salaun-Beretta, Alexandra Moura, Véronique Vernet Garnier, Didier Lepelletier, Pierre-Alexandre Hauss, Joëlle Belaisch-Amart, Didier Lepeletier, Jacob Xavier, Aline Nare, Annie Motard-Picheloup, Alain Améri, Bertrand Lioger, Jean-Valère Malfuson, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, MONALISA study group, Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., ROZIER, marie-Claire, CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections ( CNRL ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre collaborateur de l'OMS (CCOMS) des Listeria ( CCOMS ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Lariboisière, Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Agence Nationale de la Santé Publique [Saint-Maurice] ( ANSP ), Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Bacteremia/epidemiology/mortality, 0301 basic medicine, Male, Pediatrics, bacteraemia, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], Bacteremia, France/epidemiology, Infant, Newborn, Diseases, Foodborne Diseases, Meningoencephalitis, Pregnancy, Risk Factors, Vertical, Medicine, Listeriosis, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, ddc:618, diabetes, alcoholism, Hazard ratio, Foodborne Diseases/microbiology, immuno suppressive therapies, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, isolates, Population Surveillance, Female, France, Listeria monocytogenes/classification/isolation & purification, Cohort study, Adult, medicine.medical_specialty, 030106 microbiology, Notifiable disease, Listeriosis/diagnosis/epidemiology/microbiology, Context (language use), macromolecular substances, 03 medical and health sciences, Humans, study, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Public health, cirrhosis, Infant, Newborn, Infant, Diseases/epidemiology/microbiology, HIV, Mandatory Reporting, Newborn, medicine.disease, Listeria monocytogenes, infection, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious/epidemiology/microbiology, Meningoencephalitis/epidemiology/microbiology/mortality, Observational study, business, prognostic, mellitus
Abstract: International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (
Published: 2016
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24. Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95

Author: Noel Milpied, Thierry Lamy, Antoine Thyss, Steven Le Gouill, Jean François Rossi, Virginie Lucas, Eric Deconinck, Bernard Desablens, Audrey Simon, Philippe Casassus, Philippe Colombat, Jean Pierre Vilque, Jérôme Jaubert, Frédéric Maloisel, Michel Peoc'h, Charles Foussard, Olivier Tournilhac, Vincent Delwail, Remy Gressin, and Houchingue Eghbali
Subjects: Oncology, medicine.medical_specialty, Chemotherapy, Vincristine, business.industry, medicine.medical_treatment, Dacarbazine, Hematology, CHOP, medicine.disease, Peripheral T-cell lymphoma, Lymphoma, Surgery, 03 medical and health sciences, 0302 clinical medicine, ABVD, 030220 oncology & carcinogenesis, Internal medicine, medicine, T-cell lymphoma, business, 030215 immunology, medicine.drug
Abstract: Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucemies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.
Published: 2010
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25. High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years

Author: Emmanuel Gyan, Christian Berthou, Steven Le Gouill, Philippe Colombat, Roselyne Delepine, Jean-Pierre Vilque, Philippe Quittet, Bernard Desablens, Antoine Thyss, Philippe Bertrand, Eric Deconinck, Jean-François Ramée, Vincent Delwail, Patrick Michenet, Nina Arakelyan, Remi Gressin, Noel Milpied, Jérôme Jaubert, Hervé Maisonneuve, Cécile Moluçon-Chabrot, Charles Foussard, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Département de biostatistiques, Faculté de Médecine de Tours, Service de pathologie, CHU Orléans, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hospitalier La Roche-Sur-Yon, Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, CHU Grenoble, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, CHU Saint-Etienne, Clinique Catherine de Sienne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Clermont-Ferrand, CHU Bordeaux [Bordeaux], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Saas, Philippe
Subjects: Male, Oncology, Transplantation Conditioning, MESH: Immunotherapy, medicine.medical_treatment, Follicular lymphoma, Hematopoietic stem cell transplantation, Biochemistry, MESH: Lymphoma, Follicular, 0302 clinical medicine, Autologous stem-cell transplantation, Lymphoma, Follicular, MESH: Transplantation Conditioning, MESH: Middle Aged, Bone Marrow Purging, Neoplasms, Second Primary, MESH: Follow-Up Studies, Hematology, Middle Aged, Total body irradiation, MESH: Transplantation, Autologous, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Immunotherapy, MESH: Stem Cell Transplantation, MESH: Whole-Body Irradiation, MESH: Bone Marrow Purging, Whole-Body Irradiation, medicine.drug, Adult, MESH: Myeloablative Agonists, MESH: Neoplasms, Second Primary, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH: Survival Rate, Cyclophosphamide, Immunology, Transplantation, Autologous, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, Survival rate, MESH: Adolescent, Chemotherapy, MESH: Humans, business.industry, MESH: Cyclophosphamide, MESH: Adult, Cell Biology, Myeloablative Agonists, medicine.disease, MESH: Male, Surgery, Transplantation, MESH: Disease-Free Survival, business, MESH: Female, Follow-Up Studies, Stem Cell Transplantation, 030215 immunology
Abstract: Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735.
Published: 2009
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26. Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia

Author: Thérèse Aurran, Xavier Troussard, Bruno Cazin, Sophie de Guibert, Philippe Colombat, Florence Nguyen-Khac, Hervé Maisonneuve, Marie-Christine Béné, Roselyne Delepine, Elsa Tavernier, Véronique Leblond, Olivier Tournilhac, Florence Cymbalista, Stéphane Leprêtre, Christian Berthou, Caroline Dartigeas, Anne-Sophie Michallet, Pierre Feugier, Marie-Sarah Dilhuydy, Rémi Letestu, Eric Van Den Neste, Vincent Levy, Kamel Laribi, Jean-Pierre Vilque, Alain Delmer, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, 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 des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-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), 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), 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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique Adulte et de Thérapie Cellulaire, CHU Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), AP HP, Clin Res Unit, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre général des cancers du Tarn, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Registre des hémopathies malignes de Basse-Normandie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Service d'hématologie biologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-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-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Francim : Réseau français des registres des cancers, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 Hospitalier Régional Universitaire de Tours (CHRU TOURS), Nutrition, croissance et cancer (U 1069) ( N2C ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, 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 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), 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'hématologie biologique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], 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 ), 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 ), Centre François Baclesse, Centre Hospitalier Universitaire de Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I ( UdA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), 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 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Avicenne, Registre des hémopathies malignes de Basse-Normandie, Hôpital Bretonneau-CHRU Tours, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Cancer Research, medicine.medical_specialty, Cyclophosphamide, lymphoid leukemias, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Purine analogue, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Frail elderly, Chemotherapeutic approaches, immunotherapeutic approaches, [ SDV ] Life Sciences [q-bio], business.industry, Hematology, medicine.disease, Minimal residual disease, 3. Good health, Fludarabine, Oncology, 030220 oncology & carcinogenesis, Immunology, chronic lymphocytic leukemia, Rituximab, business, purine analogues, 030215 immunology, medicine.drug
Abstract: International audience; Elderly patients with chronic lymphocytic leukemia (CLL) are underrepresented in trials evaluating fludarabine, cyclophosphamide, and rituximab (FCR). We assessed four cycles of FCR with two additional rituximab doses on day 14 of cycles 1 and 2 in 194 untreated CLL patients \textgreater 65 years (median age 71.2) without del17p. Four FCR cycles were administered to 90.7% (176/194), with (n = 74) or without (n = 102) dose-delay and/or dose-reduction. A total of 50% grade 3/4 neutropenia occurred after each cycle. Only 6.2% cycles were associated with severe infection. Complete remission (CR) was achieved in 19.7%, and partial remission (PR) in 73.9% of patients. Minimal residual disease (MRD) was negative in 36.7%. Overall survival at 36 months was estimated at 87.4%. Oral FC and dose-dense rituximab is feasible and active in fit elderly CLL patients. However, myelosuppression is significant and frequent dose adaptations are required implying that these results cannot be generalized to unfit or frail elderly CLL
Published: 2016
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27. The prognostic value of hematogones in patients with acute myeloid leukemia

Author: Sylvain P, Chantepie, Jean-Jacques, Parienti, Véronique, Salaun, Khaled, Benabed, Stéphane, Cheze, Anne-Claire, Gac, Hyacinthe, Johnson-Ansah, Margaret, Macro, Gandhi, Damaj, Jean-Pierre, Vilque, and Oumedaly, Reman
Subjects: Adult, Aged, 80 and over, Male, Adolescent, Precursor Cells, B-Lymphoid, Middle Aged, Flow Cytometry, Prognosis, Risk Assessment, Survival Analysis, Disease-Free Survival, Cohort Studies, Leukemia, Myeloid, Acute, Young Adult, Bone Marrow, Recurrence, Humans, Female, Lymphocyte Count, Aged
Abstract: In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse-free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 - 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 - 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk-adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566-570, 2016. © 2016 Wiley Periodicals, Inc.
Published: 2016

28. Transfusion strategy in hematological intensive care unit: study protocol for a randomized controlled trial

Author: Sylvain Chantepie, Jean-Jacques Dutheil, Lydia Guittet, Jean-Pierre Marolleau, Jean-Jacques Parienti, Jean-Pierre Vilque, Benoît Dervaux, Fabrice Jardin, Oumedaly Reman, and Jean-Baptiste Mear
Subjects: medicine.medical_specialty, Time Factors, Blood transfusion, Bone marrow transplantation, Cost-Benefit Analysis, medicine.medical_treatment, Medicine (miscellaneous), Hematopoietic stem cell transplantation, law.invention, Hemoglobins, Study Protocol, Clinical Protocols, Predictive Value of Tests, Risk Factors, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Pharmacology (medical), Prospective Studies, Autografts, Hip surgery, Acute leukemia, Leukemia, Hematology, business.industry, Septic shock, Patient Selection, Hematopoietic Stem Cell Transplantation, Induction chemotherapy, Health Care Costs, Induction Chemotherapy, Allografts, medicine.disease, Intensive care unit, Surgery, Intensive Care Units, Treatment Outcome, Sample Size, Emergency medicine, France, Erythrocyte Transfusion, business, Biomarkers
Abstract: Background Packed red blood cell (PRBC) transfusion is required in hematology patients treated with chemotherapy for acute leukemia, autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT). In certain situations like septic shock, hip surgery, coronary disease or gastrointestinal hemorrhage, a restrictive transfusion strategy is associated with a reduction of infection and death. A transfusion strategy using a single PRBC unit has been retrospectively investigated and showed a safe reduction of PRBC consumption and costs. We therefore designed a study to prospectively demonstrate that the transfusion of a single PRBC unit is safe and not inferior to standard care. Methods The 1versus2 trial is a randomized trial which will determine if a single-unit transfusion policy is not inferior to a double-unit transfusion policy. The primary endpoint is the incidence of severe complication (grade ≥ 3) defined as stroke, transient ischemic attack, acute coronary syndrome, heart failure, elevated troponin level, intensive care unit transfer, death, new pulmonary infiltrates, and transfusion-related infections during hospital stays. The secondary endpoint is the number of PRBC units transfused per patient per hospital stay. Two hundred and thirty patients will be randomized to receive a single unit or double unit every time the hemoglobin level is less than 8 g/dL. All patients admitted for induction remission chemotherapy, auto-HSCT or allo-HSCT in hematology intensive care units will be eligible for inclusion. Sample size calculation has determined that a patient population of 230 will be required to prove that the 1-unit PRBC strategy is non-inferior to the 2-unit PRBC strategy. Hemoglobin threshold for transfusion is below 8 g/dL. Estimated percentage of complication-free hospital stays is 93 %. In a non-inferiority hypothesis, the number of patients to include is 230 with a power of 90 % and an alpha risk of 5 %. Trial Registration 14–128; Clinicaltrials.gov NCT02461264 (registered on 3 June 2015)
Published: 2015
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29. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS

Author: Philippe Bertrand, Vincent Delwail, Patrick Michenet, Annick Le Pourhiet-Le Mevel, Martine Escoffre-Barbe, Noel Milpied, Antoine Thyss, Remy Gressin, Jean-Pierre Vilque, Eric Legouffe, Bernard Desablens, Roselyne Delepine, Eric Deconinck, Philippe Colombat, Pascale Cornillet-Lefebvre, Jean-François Ramée, Arash Jenabian, Philippe Travade, Charles Foussard, Jérôme Jaubert, and Hervé Maisonneuve
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Immunology, Follicular lymphoma, Transplantation, Autologous, Biochemistry, Recurrence, Internal medicine, Humans, Medicine, Lymphoma, Follicular, Survival rate, Neoplasm Staging, Chemotherapy, business.industry, Cell Biology, Hematology, Middle Aged, medicine.disease, Chemotherapy regimen, Surgery, Survival Rate, Transplantation, Regimen, Doxorubicin, Disease Progression, Feasibility Studies, Female, France, business, Follow-Up Studies, Stem Cell Transplantation, Teniposide, medicine.drug
Abstract: Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.
Published: 2005
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30. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial

Author: Hervé Avet-Loiseau, Laurent Garderet, Mamoun Dib, Marie-Odile Petillon, Brigitte Kolb, Jean Fontan, Pascal Lenain, Brigitte Pegourie, Murielle Roussel, Jean-Pierre Vilque, Bruno Royer, H. Jardel, Philippe Casassus, Olivier Decaux, Xavier Leleu, Carine Chaleteix, Catherine Traullé, Anne-Marie Stoppa, Pascale Cony-Makhoul, Mourad Tiab, Anne Banos, Riad Benramdane, Philippe Moreau, Philippe Rodon, Cyrille Hulin, Bruno Anglaret, Lotfi Benboubker, Claire Mathiot, Olivier Fitoussi, Thomas Dejoie, Service de Médecine Interne, CH Bretagne Atlantique, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), university hospital, University Hospital, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Department of Hematology, Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Laboratoire d'Hématologie biologique, Institut Curie [Paris], Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, CRLCC Henri Becquerel, Géographie-cités ( GC ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Hospices Civils de Lyon ( HCL ), Centre François Baclesse, INSTITUT CURIE, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut des Matériaux Jean Rouxel ( IMN ), Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS ), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Curie, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, and Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Bendamustine, Melphalan, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Phases of clinical research, elderly, Autologous stem-cell transplantation, Prednisone, hemic and lymphatic diseases, Internal medicine, medicine, bendamustine, Online Only Articles, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, relapse, [ SDV ] Life Sciences [q-bio], business.industry, Bortezomib, Hematology, medicine.disease, 3. Good health, Surgery, Thalidomide, multiple myeloma, business, medicine.drug
Abstract: In patients with multiple myeloma (MM) not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), the 2 following options are recommended as part of front-line treatment and approved based on data from randomized phase III trials: melphalan/prednisone/thalidomide (MPT), or
Published: 2015
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31. Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation

Author: Pierre Fenaux, Anne Vekhoff, A Sadoun, Arnaud Pigneux, L. Degos, N. Gratecos, Jean-Pierre Vilque, Xavier Thomas, T de Revel, Claude Gardin, Agnes Buzyn, P Naccache, Philippe Travade, Françoise Huguet, Nathalie Fegueux, Frédéric Maloisel, J.Y. Cahn, Christian Berthou, Christine Chomienne, Catherine Cordonnier, Oumedaly Reman, Agnès Guerci, P Kotoucek, Aspasia Stamatoullas, and Hervé Dombret
Subjects: Acute promyelocytic leukemia, Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Gastroenterology, Surgery, Transplantation, Leukemia, Oncology, Internal medicine, Cytarabine, Medicine, Autologous transplantation, business, Etoposide, medicine.drug
Abstract: The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts >5 x 10(9)/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging.
Published: 2000
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32. Interferon Alfa-2b Combined with Cytarabine versus Interferon Alone in Chronic Myelogenous Leukemia

Author: François Guilhot, Claude Chastang, Mauricette Michallet, Agnès Guerci, Jean-Luc Harousseau, Frédéric Maloisel, Réda Bouabdallah, Denis Guyotat, Nathalie Cheron, Franck Nicolini, Jean-François Abgrall, Joseph Tanzer, Maurice Navarro, Dominique Bordessoule, Patrick Morice, Norbert Ifrah, Henri Rochant, Jean-Pierre Vilque, Martine Delain, Francis Bauters, and Joëlle Guilhot
Subjects: medicine.medical_specialty, business.industry, Alpha interferon, General Medicine, medicine.disease, Chronic phase chronic myelogenous leukemia, Gastroenterology, Surgery, medicine.anatomical_structure, Interferon, Internal medicine, medicine, Cytarabine, Bone marrow, business, Complete Hematologic Response, Interferon alfa, medicine.drug, Chronic myelogenous leukemia
Abstract: Background Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine. Methods Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome–positive cells in the bone marrow) at 12 months. Results The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon–cytarabine group (360 patients) as compared wit...
Published: 1997
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33. Bendamustine-Based (BeEAM) Conditioning before Autologous Stem Cell Transplantation: Result of a French Multicenter Study of 386 Patients from Lysa Centers

Author: Anne-Claire Gac, Olivier Tournilhac, Ibrahim Yakoub-Agha, Benjamin Carpentier, Emmanuel Gyan, Sandra Malak, Caroline Delette, Eric Durot, Mohamed Amine Bekadja, Emmanuelle Tchernonog, Roch Houot, Momar Diouf, Thomas Gastinne, Adrien Chauchet, Sylvain Chantepie, Arnaud Jaccard, Marie-Virginie Larcher, Bachra Choufi, Ahmad Ibrahim, Rene-Olivier Casasnovas, Luc Mathieu Fornecker, Reda Garidi, Gandhi Damaj, Carole Soussain, Krimo Bouabdallah, Frederic Peyrade, Stéphanie Guidez, Jean-Pierre Vilque, Adrian Tempescul, and Remy Gressin
Subjects: Bendamustine, medicine.medical_specialty, Immunology, Biochemistry, Gastroenterology, Nephrotoxicity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autologous stem-cell transplantation, Intensive care, Internal medicine, Medicine, Creatinine, business.industry, Cell Biology, Hematology, medicine.disease, Surgery, Regimen, chemistry, 030220 oncology & carcinogenesis, Mantle cell lymphoma, business, Packed red blood cells, 030215 immunology, medicine.drug
Abstract: Unavailability of Carmustine and its dramatically increased cost by nearly 10 fold has led to its replacement by bendamustine (Be) and an increase use of Bendamustine-based (BeEAM) conditioning regimen before autologous stem cell transplantation for lymphoma. The aim of this study was to evaluate the safety of the BeEAM regimen in the real life use in several French centers. Median age of the 386 patients (233 male, 153 female) was 55 years (17-72). The majority of patients had aggressive B-cell (40%), follicular (17%), Hodgkin's (17%) and mantle cell lymphoma (15%). Two hundred and forty six patients (64%) were transplanted after 2nd line chemotherapy and the median number of prior lines of chemotherapy of 2 (1-9). Two hundred and sixty patients (67%) had received prior platinum chemotherapy and only 4% had a history of prior chronic renal failure (Table 1). The median creatinine level at conditioning initiation was 71(36-206) µmol/l. Be was administered at a median dose of 191 mg/m2/day (50-250) on day -7 and -6. Thirty two percent received 100-160 mg/m²/d and 58% of patients received more than 160 mg/m²/d. Median 24h-hydration volume was 3 l (1-6) which began within median time of 18 h (1-72) prior to conditioning initiation. The median duration time of Be perfusion was 60 min (30-143). Grade 1-4 acute renal failure (ARF) was reported in 107 cases (28%) (G ≥2; 34%) and appeared after a median time of 2 days (1-18) after conditioning start. Melphalan dosage was reduced, due to renal failure, in 10% of patients (Table 2). 84% of patients normalized their creatinine level within a median time of 10 days (1-77). The most frequent reported Grade 1-4 toxicities were mucositis (84%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%) and cardiac rhythm disorders (4%). Opportunistic infection was documented in 9.5% of patients, HHV6 reactivation in 6% of patients. Ten percent of patients needed intensive care management and toxic death was estimated at 5% (Table 3). Patients received a median of 3 (0-34) packed red blood cells and 4 (0-56) platelets units. The median time to neutrophils > 0.5 G/L and platelets > 20 G/L were 10 (0-50) and 12 (0-210) days. The median time of hospital stay was 23 (12-85) days. In comparison with the group of patient without renal failure, the group of patients with ARF had older age (58 vs 54), higher rate of pre-transplant chronic renal failure (10% vs 1%), higher rate of platinum treatment (77% vs 64%), higher day1 creatinine level (81 vs 69) and received higher median bendamustine (199 vs 182). Colitis (p=0.039), pneumonitis (p=0.008), cardia arrhythmia (p=160mg/m2 and age were independent prognostic factors for ARF. A three-point clinical predictor score for acute renal failure was identified and included creatinine level>65µmol/l, bendamustine dose >160mg/m² and age>57 years. ARF stratified by score, was 4% with score 0, 17% with score 1, 30% with score 2 and 45% with score 3. In conclusion, BeEAM induced 5% non-relapse mortality with high rate of renal toxicity. A simple, three-point scoring system can stratify patients by levels of risk for ARF. Rapid identification of higher risk patients may allow a reduction of the bendamustine dose to improve clinical outcomes. Prospective comparative studies are needed to confirm toxicity extents of this conditioning as compared with other type of high dose therapy. Disclosures Soussain: Pharmacyclics: Research Funding; Celgene: Research Funding; Roche: Research Funding. Malak:Novartis: Membership on an entity's Board of Directors or advisory committees.
Published: 2016
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34. Rituximab maintenance after induction with abbreviated FCR in previously untreated elderly (≥ 65 years) CLL patients: Results of the randomized CLL 2007 SA trial from the French FILO Group (NCT00645606)

Author: Alain Delmer, Philippe Rodon, Christian Berthou, Florence Nguyen-Khac, Marie C. Béné, Julie Léger, Eric Van Den Neste, Marie-Sarah Dilhuydy, Véronique Leblond, Philippe Colombat, Jean-Pierre Vilque, Hervé Maisonneuve, Thérèse Aurran, Sophie de Guibert, Stéphane Leprêtre, Vincent Levy, Beatrice Mahe, Caroline Dartigeas, Rémi Letestu, and Pierre Feugier
Subjects: 030213 general clinical medicine, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, chemical and pharmacologic phenomena, Immunotherapy, 03 medical and health sciences, 0302 clinical medicine, Oncology, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Internal medicine, medicine, Rituximab, business, medicine.drug
Abstract: 7505Background: A promising concept to improve outcome in CLL is maintenance with immunotherapy after induction with FCR to improve quality and duration of response. Methods: Treatment-naive, ≥ 65 ...
Published: 2016
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35. Hematogones: a new prognostic factor for acute myeloblastic leukemia

Author: Sylvain Chantepie, Jean-Jacques Parienti, Florence Truquet, Jean Pierre Vilque, Oumedaly Reman, Véronique Salaun, Margaret Macro, and Stéphane Cheze
Subjects: Oncology, medicine.medical_specialty, Acute myeloblastic leukemia, Immunology, Biochemistry, Disease-Free Survival, Recurrence, Internal medicine, medicine, Humans, Leukocytosis, Aged, Acute leukemia, Hematology, Hematologic Tests, business.industry, Precursor Cells, B-Lymphoid, Hazard ratio, Remission Induction, Myeloid leukemia, Cell Biology, Middle Aged, medicine.disease, Prognosis, Chemotherapy regimen, Survival Analysis, Confidence interval, Leukemia, Myeloid, Acute, medicine.symptom, business
Abstract: Acute myeloid leukemia (AML) patient outcomes remain heterogeneous, and new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors, which increase in number in hematologic diseases. The prognostic impact of the presence of detectable HGs on the leukemia-free survival (LFS) and overall survival of 120 consecutive patients with AML in first complete remission was investigated by flow cytometry. Patients who had HG levels more than 0.01% had a significantly better median LFS (29.2 vs 11.7 months; P = .001) and overall survival (not reached vs 23.5 months; P = .011). According to Cox analysis, an HG level more than 0.01% was an independent predictor of LFS (hazard ratio = 0.5; 95% confidence interval, 0.28-0.90, P < .03) when age, leukocytosis, the number of chemotherapy cycles, and the standardized cytogenetic and molecular risk subgroups were controlled for. These results indicate that HG analysis may help to define the risk of relapse in AML patients.
Published: 2010

36. Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95

Author: Audrey, Simon, Michel, Peoch, Philippe, Casassus, Eric, Deconinck, Philippe, Colombat, Bernard, Desablens, Olivier, Tournilhac, Houchingue, Eghbali, Charles, Foussard, Jerome, Jaubert, Jean Pierre, Vilque, Jean François, Rossi, Virginie, Lucas, Vincent, Delwail, Antoine, Thyss, Frederic, Maloisel, Noel, Milpied, Steven, le Gouill, Thierry, Lamy, and Rémy, Gressin
Subjects: Adult, Male, Adolescent, Lymphoma, T-Cell, Peripheral, Middle Aged, Vinblastine, Survival Analysis, Dacarbazine, Bleomycin, Young Adult, Treatment Outcome, Doxorubicin, Vincristine, Antineoplastic Combined Chemotherapy Protocols, Humans, Prednisone, Female, Ifosfamide, Cisplatin, Cyclophosphamide, Aged, Etoposide, Neoplasm Staging
Abstract: Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.
Published: 2010

37. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

Author: Jean Pierre Vilque, Gérard Lepeu, Emmanuel Gyan, Marie Pierre Moles, Sylvie Caulet-Maugendre, Jérôme Cornillon, Marc Colonna, Philippe Solal Celigny, Steven Le Gouill, Remy Gressin, Ghandi Damaj, Abderrazak El Yamani, Jean François Rossi, Eric Deconinck, Philippe Colombat, Thierry Lamy, Philippe Casassus, Bernadette Corront, Olivier Tournilhac, Hervé Maisonneuve, Saas, Philippe, 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), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centres d'addictologies - Région Centre, CHU Clermont-Ferrand, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier du Mans, Centre Hospitalier Le Mans (CH Le Mans), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'hématologie et oncologie clinique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Henri Duffaut (Avignon), CHU Amiens-Picardie, Clinique Victor Hugo [Le Mans], Centre hospitalier La Roche-Sur-Yon, Centre hospitalier d'Annecy, CH Annecy, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre des cancers de l'Isère, registre des Cancers de l'Isère, French GOELAMS group, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), 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)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Male, autologous stem cell transplantation, Lymphoma, Mantle-Cell, Gastroenterology, Dexamethasone, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Autologous stem-cell transplantation, chlorambucil, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, education.field_of_study, Cytarabine, Hematology, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Treatment Outcome, B symptoms, Vincristine, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Female, medicine.symptom, Rituximab, Adult, medicine.medical_specialty, Neutropenia, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Population, mantle cell lymphoma, Editorials and Perspectives, Transplantation, Autologous, Disease-Free Survival, Drug Administration Schedule, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, education, Aged, Performance status, business.industry, medicine.disease, Thrombocytopenia, Surgery, Transplantation, Regimen, Ki-67 Antigen, Mantle cell lymphoma, business, Follow-Up Studies, Stem Cell Transplantation, 030215 immunology
Abstract: International audience; Background There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation. DESIGN AND METHODS: Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed. RESULTS: The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3-4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3-4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389).
Published: 2010
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38. Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma

Author: Charles Foussard, E. Chamorey, J.L. Harrousseau, M. Fabbro, Hervé Maisonneuve, Jean-Pierre Vilque, G. Lepeu, Vincent Delwail, Antoine Thyss, Remy Gressin, F. Peyrade, B. Richard, and Jean François Rossi
Subjects: Male, Cancer Research, medicine.medical_specialty, Vincristine, Neutropenia, CHOP, Gastroenterology, Dexamethasone, Disease-Free Survival, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Ifosfamide, Prospective Studies, Cyclophosphamide, Aged, Epirubicin, Etoposide, Mitoxantrone, business.industry, Lymphoma, Non-Hodgkin, General Medicine, medicine.disease, Pyruvaldehyde, Survival Analysis, Thrombocytopenia, Non-Hodgkin's lymphoma, Surgery, Regimen, Treatment Outcome, Oncology, Prednisone, Female, business, medicine.drug
Abstract: Objective: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (≧65 years) with aggressive non-Hodgkin’s lymphoma (NHL). Methods: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. Results: Neutropenia (p < 10–5), anemia (p < 10–5) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). Conclusion: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.
Published: 2004

39. Alpha-interferon in combination with cytarabine in children with Philadelphia chromosome-positive chronic myeloid leukemia

Author: François Demeoq, Jean-Francoise Boccara, Jean-Pierre Vilque, François Guilhot, Joelle Guilhot, Denis Guyotat, Frédéric Millot, Marc Wetterwald, Pauline Brice, N Philippe, and Antoine Thyss
Subjects: medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Alpha interferon, Antimetabolite, Gastroenterology, Leukocyte Count, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Child, Interferon alfa, Metaphase, Chemotherapy, business.industry, Cytarabine, Myeloid leukemia, Interferon-alpha, Hematology, medicine.disease, Treatment Outcome, Oncology, Pediatrics, Perinatology and Child Health, Immunology, business, Complete Hematologic Response, Spleen, medicine.drug, Chronic myelogenous leukemia
Abstract: Background: Philadelphia chromosome-positive chronic myelogenous leukemia (CML) is a rare disease in children, and the optimal therapy is not clearly defined in these patients when a human leukocyte antigen-identical donor is not available. The present work focuses on the therapeutic efficacy and the toxicity of interferon (IFN) a2b in combination with cytosine arabinosine (Ara-C) in patients younger than age 18 years enrolled in the randomized trial CML 91, which compared the efficacy of IFN and cytosine arabinoside (Ara-C) with IFN alone in 810 patients with CML in the chronic phase. Patients and Methods: Twelve patients younger than age 18 years were enrolled in the randomized trial CML 91. Hydroxyurea and IFN (5 million units/m 2 , once a day) were given as initial treatment in all patients. After randomization, six patients received IFN (5 million units/m 2 , once per day) and Ara-C (20 mg/m 2 for 10 days each month) (IFN plus Ara-C group), and six patients received IFN alone (5 million units/m 2 once per day) (IFN group). Results: Six months after the beginning of the treatment, a complete hematologic response was obtained in all the patients in the IFN plus Ara-C group and in four patients in the IFN group. A major cytogenetic response was observed in three patients in the IFN plus Ara-C group and in two patients in the IFN group. Five patients from the IFN group who crossed over to receive Ara-C did not experience additional hematologic toxicity. Three patients in the IFN plus Ara-C group and two from the IFN group are alive, in major cytogenetic response, with a follow-up of 18 to 48 months. Conclusion: The combination of IFN and Ara-C induces complete hematologic and major cytogenetic responses and is well tolerated in patients younger than age 18 years with CML. This combination may offer an alternative to bone marrow transplantation in children in the chronic phase of CML without a histocompatible donor.
Published: 2002

40. Frontline Therapy with the Ribvd Regimen Elicits High Clinical and Molecular Response Rates and Long PFS in Elderly Patients Mantle Cell Lymphoma (MCL); Final Results of a Prospective Phase II Trial By the Lysa Group

Author: Hacene Zerazhi, Loic Ysebaert, Remy Gressin, Ghandi Damaj, Bertrand Joly, Jean Pierre Vilque, Guillaume Cartron, Cecile Chabrot, Krimo Bouabdallah, Yazid Arkam, Fabrice Jardin, Marie Pierre Moles, Jean Michel Pignon, Véronique Dorvaux, Christiane Mounier, Jehan Dupuis, Selim Corm, Roch Houot, J. Fleury, Margareth Macro, Katell Le Du, Lionel Karlin, Nicolas Daguindau, Nadine Morineau, Laurent Voillat, Magda Alexis, Reda Garidi, Sylvain Carras, Mary Callanan, Jean Fontan, Anne Banos, Luc Fornecker, Pierre Feugier, Sandy Amorin, Steven Le Gouill, Caroline Dartigeas, Adrian Tempescul, and Vincent Delwail
Subjects: Bendamustine, medicine.medical_specialty, business.industry, Immunology, Phases of clinical research, Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, Gastroenterology, Surgery, Regimen, Maintenance therapy, Internal medicine, medicine, Rituximab, Mantle cell lymphoma, business, Febrile neutropenia, medicine.drug
Abstract: Background: Eight RCHOP/21 cycles followed by Rituximab maintenance is considered the standard of care for first line therapy in elderly MCL patients in Europe (1). However,complete clinical (CR) and molecular responses (MR) to therapy remain suboptimal(CR rate 30-35%, MR after 8 cycles 67 %). Regimen combining Rituximab and Bendamustine and more recently proteasome inhibitor Bortezomib (Velcade®) with CHOP regimen (VcR-CAP) demonstrated superior CR rates and PFS compared to R-CHOP. We have investigated the RiBVD regimen (Rituximab, Bendamustine,Velcade® and Dexamethasone) in a prospective phase II trial by the LYSA group. Aims of the study: The primary objective was to improve the median PFS by 6 months over the current 18 months PFS obtained with RCHOP when given without maintenance (ref Lenz, JCO 2005). The secondary objectives were to investigate the prognostic impact of molecular and FDG-PET responses on survival.. Methods and Material: All patients aged 65 or older with a diagnosis of MCL were treated by the RiBVD regimen if they fulfilled the following inclusion criteria: AAstage II-IV, PS < 3, no other neoplasm, no active HIV or HBV or HCV infections, no renal (creatinin clearance > 20ml/mn) or cardiac dysfunction, no diabetes. The RiBVD regimen was administered every 4 weeks with Rituximab 375 mg/m² IV on day(D)1, Bendamustine 90 mg/m² IV on D1, 2, Dexamethasone 40 mg IV on D2 and Bortezomib (Velcade®) 1.3 mg/m² subcutaneously on D1, 4, 8 and 11. Primary prophylaxis with valacyclovir was mandatory for Herpes virus reactivation, but there was no recommendation for bacterial prevention. Patients were scheduled to receive a total of 6 cycles, if they achieved at least PR at 4 cycles. The IWG criteria, with and without FDG-PET, were used to define responses after 4 and 6 cycles. FDG-PET response was evaluated in each center with the five-point scale visual method of Deauville. Molecular responses (MR) were evaluated centrally by RQ-PCR using patient specific IGH VDJ targets as previously described (2). Results: Seventy six patients were recruited in one year (from November 2011 to December 2012), 74 were evaluable [2 patients were excluded because HBV positivity (n=1) or misdiagnosis (n=1)]. Fifty four samples were centrally reviewed for diagnosis, 45 were classic form of MCL, 9 pleomorphic variant and one patient had a DLBCL. Clinical characteristics of the 74 patients were: Median age 73 yo (64-83), sex ratio M/F = 2 (49/25), AAstage II/III-IV = 4/70, PS 0-1/2 = 63/11, MIPIscore low/intermediate/high= 3/19/50 (2 undetermined). The median follow-up is 21 months. Thirteen patients died because of lymphoma progression (n=7), cardiac arrest (n=2) or in one case each,pneumonia, Progressive Multifocal LeukoEncephalopathy, pancreatic carcinoma or of unknown causes. After 4 cycles the ORR was 86% (n=64) and CR/CRu 57% (n=42). After 6 cycles, the CR/CRu raised to 74% (n=55) the PR rate was 9% (n=7), 2 patients had a stable disease, 4 progressed and 5 had died during the treatment. The complete MR rate after 6 months on blood samples or bone marrow was respectively 83% (43/50) and 74 % (32/43). At 24 months, the PFS was 69% and the OS 80%. The MIPI score (high vs low/int) and the blood MR after 6 cycles were the only two statistically prognostic factors for PFS and OS. Toxicities were essentially hematologic with grade 3 or 4 neutropenia and thrombocytopenia in 51% and 36% of the cases, respectively. The main grade 3 or 4 extra-hematologic toxicities were fatigue (19%), neuropathy (14%), cardiac (7%) or febrile neutropenia (5%). Conclusion: The RiBVD regimen can be safely administered as first line therapy to elderly patients with MCL. Toxicities are mild and manageable. With 74% of CR/CRu, a 2 year PFS of 69% and 86% of patients achieving an MRD negative status in the blood after 6 cycles, without maintenance therapy, the RiBVD regimen is identified as a highly effective, well tolerated, first line treatment for elderly MCL patients. Reference : 1 - Kluin Nelemans HC et al, NEJM 2012, 2 - Gimenez E et al, BJH 2012 Disclosures Gressin: mundipharma: Consultancy. Off Label Use: Bendamustine and Bortezomib did not have authorization to their use in first line for MCL in France. Karlin:Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Le Gouill:Mundipharma: Honoraria; Roche: Honoraria; Janssen: Consultancy.
Published: 2014
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41. Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase

Author: Claude Chastang, J Attal, Karim Belhadj, Frédéric Maloisel, Josy Reiffers, Agnès Guerci, Jean-Pierre Vilque, J-L Harousseau, Mauricette Michallet, F Bauduer, G Tertain, M. Blanc, M Chabin, Nathalie Cambier, Martine Delain, Norbert Ifrah, B Pegourie-Bandelier, Jean Briere, P. Morice, Eric Solary, JF Abgrall, Philippe Rousselot, François Guilhot, Joelle Guilhot, Diane Coso, and Denis Guyotat
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, medicine.drug_class, medicine.medical_treatment, Administration, Oral, Interferon alpha-2, Gastroenterology, Antimetabolite, Oral administration, Risk Factors, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, medicine, Cytidine Monophosphate, Humans, Aged, Chemotherapy, Arabinonucleotides, Dose-Response Relationship, Drug, business.industry, Interferon-alpha, Hematology, Middle Aged, medicine.disease, Prognosis, Recombinant Proteins, Surgery, Survival Rate, Oncology, Tolerability, Toxicity, Leukemia, Myeloid, Chronic-Phase, Cytarabine, Female, business, Complication, Chronic myelogenous leukemia, medicine.drug, Follow-Up Studies
Abstract: Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.
Published: 2001

42. Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-alpha

Author: Mauricette Michallet, A. Belhabri, P.-Y. Peaud, D. Fiere, Karin Bilger, Charles Dumontet, A Devidas, C. Charrin, B Salles, Bernadette Corront, A. Thiébaut, Jean-Pierre Vilque, Xavier Thomas, Denis Guyotat, C Vigouroux, and I Philip
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, Neutrophils, Alpha interferon, Gastroenterology, Autologous stem-cell transplantation, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, medicine, Autologous transplantation, Humans, Progenitor cell, Busulfan, Melphalan, Interferon alfa, business.industry, Hematopoietic Stem Cell Transplantation, Interferon-alpha, Hematology, Middle Aged, medicine.disease, Hematopoietic Stem Cell Mobilization, Granulocyte colony-stimulating factor, Surgery, Transplantation, Oncology, Female, business, medicine.drug, Chronic myelogenous leukemia
Abstract: In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon alpha (IFN-alpha) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 microg/kg/day x 5 days) given subcutaneously while continuing IFN-alpha therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 x 10(9)/l (6.9-108) white blood cells, 7.2 x 10(8)/kg (2.2-16.6) mononuclear cells, 39 x 10(4)/kg (4.8-403.5) CFU-GM and 4.2 x 10(6)/kg (0-58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-alpha therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-alpha therapy duration, although there was a significant impact from GM-CSF administration (P=0.01). After transplantation, 26 patients received IFN-alpha alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-alpha responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed.
Published: 2001

43. Bendamustine, Bortezomib and Dexamethasone (BVD) In Elderly Patients With Multiple Myeloma In First Relapse: Final Analysis Of The Intergroupe Francophone Du Myelome (IFM) 2009-01 Trial

Author: Philippe Rodon, Cyrille Hulin, Brigitte Pegourie, Mourad Tiab, Bruno Anglaret, Lotfi Benboubker, Henry Jardel, Olivier Decaux, Brigitte Kolb, Murielle Roussel, Laurent Garderet, Xavier Leleu, Olivier Fitoussi, Carine Chaleteix, Philippe Casassus, Pascal Lenain, Bruno Royer, Anne Banos, Riad Benramdane, Pascale Cony-Makhoul, Mamoun Dib, Jean Fontan, Anne-Marie Stoppa, Catherine Traulle, Jean-Pierre Vilque, Marie-Odile Petillon, Claire Mathiot, Hervé Avet-Loiseau, and Philippe Moreau
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Abstract: Background Prognosis of relapses is severe in elderly multiple myeloma (MM). In recent studies, median survival at progression after 1st line therapy was between 9 and 13 months (T. Facon, Lancet 2007; C. Hulin, J Clin Oncol 2009). Bortezomib (V) plus dexamethasone (D) is a major regimen in the treatment of relapses. Bendamustine (B) demonstrated to be highly active in advanced MM. The IFM 2009-01 trial evaluates the combination of B, V and D in elderly patients with progressive MM on or after 1stline treatment. Methods Phase 2 IFM 2009-01 trial was dedicated to patients older than 65 years in 1st relapse or refractory to 1st line therapy. Inclusion criteria were measurable disease, PS ECOG 0-2, ANC > 1.5x109/l, platelets > 100x109/l, serum creatinine level < 250 mcmol/l, AST and ALT < 3xULN. Pts with prior exposure to bortezomib were excluded. Treatment regimen was B 70 mg/m2 day 1-8, V 1.3 mg/m2 day 1-8-15-22 and D 20 mg day 1-8-15-22 every 28 days. 6 cycles were administered. Responders were assigned to receive maintenance treatment with 6 additional cycles administered 1 month out of 2. Response was evaluated according to IMWG criteria. Response rate was the primary objective. Progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Results From 03/2010 to 07/2011, 73 pts were included. Median age was 75.8 years (range 66-86). Median time from diagnosis to inclusion was 29 months. All pts received only 1 prior line of therapy: Melphalan-Prednisone (MP) in 12, MP-Thalidomide in 42, Lenalidomide-Dexamethasone (LD) in 14, other IMiD-based regimen in 5. Median treatment cycles administered was 7 (1-12). 51 pts (69.8%) achieved at least partial response [best response CR: 10 pts (13.6%), VGPR: 12 pts (16.5%), PR: 29 pts (39.7%), MR: 4 pts (5.5%), SD: 5 pts (6.8%), progression: 12 pts (16.5%), unrelated early death: 1 pt (1.3%)]. Median PFS was 10.8 months (95%CI: 7-18.2 months) and median OS 23 months (15.4-27.5). Adverse prognostic factors for PFS were PS ECOG 2 (p=0.0002), beta 2 microglobulin level > 3.5 mg/l (p=0.0006) and del17p (p=0.01). 26 pts (35.6%) completed the planned 12 cycles of treatment. Cause of treatment discontinuation was progressive MM in 30 pts (41.1%), failure to achieve PR in 5 pts (6.8%), adverse event in 10 pts (13.6%), patient refusal and unknown 1 pt (1.3%) each. 37 pts (50.6%) had died at time of final analysis. Cause of death was MM in 30 pts, sepsis in 5 pts, renal failure in 1 pt and unrelated in 1 pt. Grade 3-4 adverse events were neutropenia: 14 pts (19.1%), thrombocytopenia: 8 pts (10.9%), sepsis: 14 pts (19.1%), gastro-intestinal: 6 pts (8.2%), anaphylaxis: 2 pt (2.7%). Grade 2 peripheral neuropathy occurred in 8 pts (10.%) and grade 3 in 3 pts (4.1%). Conclusions In this elderly population with poor prognosis MM, BVD combination provides a high overall response rate and manageable toxicity. These results compare favourably with those achieved with VD or LD. Disclosures: Roussel: CELGENE: Honoraria; JANSSEN: Honoraria. Leleu:CELGENE: Honoraria; JANSSEN: Honoraria. Cony-Makhoul:BMS: Honoraria. Avet-Loiseau:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Moreau:Janssen: Honoraria; Janssen and Millennium: Membership on an entity’s Board of Directors or advisory committees.
Published: 2013
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44. Avascular necrosis of the femoral head as a complication of chronic myelogenous leukaemia

Author: Jean-Paul Eschard, Jean Leone, Jean-Pierre Vilque, J. C. Etienne, Bernard Pignon, Jean-Loup Pennaforte, and Claude Marcus
Subjects: Male, medicine.medical_specialty, medicine.diagnostic_test, Adolescent, business.industry, Magnetic resonance imaging, Avascular necrosis, Femur Head, medicine.disease, Magnetic Resonance Imaging, Surgery, Radiography, Femoral head, medicine.anatomical_structure, Bone scintigraphy, Femur Head Necrosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Orthopedic surgery, medicine, Humans, Radiology, Nuclear Medicine and imaging, Femur, business, Complication, Femoral neck
Abstract: A 17-year-old male patient complaining of intense pain in his right hip was found to be suffering from chronic myelogenous leukaemia. Preliminary X-rays and bone scintigraphy did not suggest avascular necrosis of the femoral head. Magnetic resonance imaging (MRI) did, however, reveal leukaemic infiltration of the femoral neck and generalised ischeamia in the femoral head. Further, MRI carried out 4 months later disclosed typical signs of osteonecrosis, despite previous indications of an improvement under chemotherapy. Flattening of the head of the femur appeared in radiographs taken in the 9th month. In the 12th month, recurrence of pain made it necessary to perform a total hip arthroplasty. Anatomo-pathological investigation confirmed both the necrosis and the leukaemic invasion.
Published: 1996

45. Treatment of acute myelogenous leukaemia in patients aged 50-65: idarubicin is more effective than zorubicin for remission induction and prolonged disease-free survival can be obtained using a unique consolidation course. The Goelam Group

Author: Bruno Audhuy, Jean Briere, J L Harousseau, Patrick Hervé, P. Berthaud, B. Pignon, A. Sadoun, Jean Pierre Vilque, Laurence Baranger, Sylvie François, P. Y. Leprise, Bernard Desablens, Denis Guyotat, Bruno Lioure, Claude Linassier, Francis Witz, Denis Caillot, Philippe Casassus, V. Polin, Jean-Yves Cahn, P. Hurteloup, and Christian Berthou
Subjects: Male, medicine.medical_specialty, Randomization, Anthracycline, medicine.medical_treatment, Gastroenterology, Disease-Free Survival, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, Internal medicine, Medicine, Idarubicin, Humans, Aged, Chemotherapy, Antibiotics, Antineoplastic, business.industry, Zorubicin, Daunorubicin, Remission Induction, Hematology, Middle Aged, Survival Analysis, Surgery, Clinical trial, Survival Rate, Leukemia, Myeloid, Acute, Treatment Outcome, chemistry, Cytarabine, Female, business, medicine.drug
Abstract: From December 1987 to June 1992, 251 patients aged 50–65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi-institutional randomized clinical trial. Induction therapy consisted of Ara-C (200 mg/m2, continuous infusion, days 1–7) with either zorubicin (ZRB) (200 mg/m2, i.v., days 1–4) or idarubicin (IDR) (8 mg/m2, i.v., days 1–5). Consolidation therapy consisted of a single course of intensive chemotherapy with high-dose Ara-C (3 g/m2, 3 h infusion, q 12 h, days 1–4) and m-Amsa (100 mg/m2/d, i.v., days 5–7). The complete remission (CR) rate was (73%) with Ara-C/IDR versus (60%) with Ara-C/ZRB (P = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow-up of 73 months, the median disease-free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event-free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms. The study shows that in patients aged 50–65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.
Published: 1996

46. Safety and Efficacy of Abbreviated Induction with Oral Fludarabine (F) and Cyclophosphamide (C) Combined with Dose-Dense IV Rituximab (R) in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL) Aged > 65 years : Results of a Multicenter Trial (LLC 2007 SA) On Behalf of the French Goelams/Fcgcll-WM Intergroup

Author: Xavier Troussard, Roselyne Delepine, Marie-Sarah Dilhuydy, Bruno Giraudeau, Philippe Colombat, Florence Nguyen-Khac, Thérèse Aurran, Vincent Levy, Anne-Sophie Michallet, Sophie de Guibert, Caroline Dartigeas, Pierre Feugier, Hervé Maisonneuve, Olivier Tournilhac, Véronique Leblond, Bruno Cazin, Alain Delmer, Kamel Laribi, Stéphane Leprêtre, Eric Van Den Neste, Rémi Letestu, Marie-Christine Béné, Christian Berthou, Jean Pierre Vilque, and Florence Cymbalista
Subjects: medicine.medical_specialty, Intention-to-treat analysis, Randomization, Cyclophosphamide, business.industry, Immunology, Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, Gastroenterology, Fludarabine, Surgery, Internal medicine, Multicenter trial, Medicine, Rituximab, business, Febrile neutropenia, medicine.drug
Abstract: Abstract 434 Introduction: The German CLL8 trial has demonstrated that addition of R to FC improves quality and durability of response in CLL (Hallek et al, 2010), which has led to the recommendation of FCR as first line therapy for fit patients. Although elderly patients were included in the CLL8 trial (up to 81 y-old), the median age of the cohort was 61 y, thus at least 10 y younger than median age at CLL diagnosis. The elderly population is underrepresented in clinical trials and it is still not clear how FCR should be applied in this subgroup. In December 2007, the French intergroup launched the LLC 2007 SA trial (NCT00645606) in which CLL patients aged > 65 y receive an induction with abbreviated FCR followed by randomization between observation or maintenance with rituximab. We now report the safety and efficacy of the induction part in the first 200 patients enrolled in this study. Patients and methods: Stage B or C previously untreated fit (CIRS ≤ 6, CCR ≥ 60 ml/min, PS ≤ 1) CLL patients aged > 65 y needing treatment (NCI criteria) were included. Patients with del17p and/or Matutes scoring < 4 were excluded. From these 200 first patients included, 6 were removed because of incorrect inclusion (n=4) or consent withdrawal (n=2). In total, 194 patients (included between Dec/07 and Feb/10) were analyzed. FCR consisted of four monthly cycles of oral FC (F 40 mg/msq/d and C 250 mg/msq/d, × 3d) and iv R (375 mg/msq d1 cycle 1, 500 mg/msq d14 cycle 1, d1 and 14 of cycle 2, and d1 of cycles 3 and 4). Response was assessed by NCI criteria. MRD analysis was done using 6-color FCM in PB and BM. No later than 90 d after the last FCR, patients were further randomized as per protocol. Disease outcome after randomization remains completely blinded to date. Results: The median age was 71 y (range 65–85) and 65% were males. 83% had CIRS between 0 and 3. Binet stage was B in 127 (65.5%) and C in 67 (34.5%). Median (n=143) Beta-2-microglobulin was 4 mg/L (range 2–8). Fifty-six % had unmutated IgVH and FISH revealed 18% with del11q, 15% with trisomy 12, and 57% with del13q. Karyotype (ODN+IL2-stimulated) was abnormal in 67%. Balanced and unbalanced translocations were seen in 16% and 17%, respectively. Complex (>2 abn) karyotype occurred in 14% of the patients. Toxicity: 167 (86%) received all four cycles of FCR. Only 4.6% and 3.2% of patients did not receive d14 rituximab at cycle 1 and 2, respectively. 158 patients (81%) could proceed to the randomization (the main reason for failure was insufficient marrow recovery). Dose delay (by ≥ 1 w) and dose reduction (by ≥ 25% of F and C) for cycles 2, 3, and 4 were 12% and 7%, 14% and 8%, 15% and 11%, respectively. Neutropenia g3/4 occurred after cycle 1, 2, 3 and 4, in 46% (19% g4), 50% (21% g4), 53% (29% g4), and 46% (26% g4) of the patients. G-CSF was given in 32%, 46%, 48%, and 52% of them after cycles 1, 2, 3, and 4. G4 thrombocytopenia occurred in less than 2% of the cycles. G3/4 anemia was seen in 11%, 7%, 6%, and 3% of the patients after cycle 1, 2, 3, and 4, respectively. G 3/4 infectious events occurred in 6.2%, 4.8%, 7.6%, and 6.2% of the patients after each of the 4 cycles. Seventy SAE (including 46 febrile neutropenia and/or documented infection) were declared in 53 patients during the induction and the period of recovery prior to randomization. In total, 6.3% of the 732 cycles were followed by febrile neutropenia or infection qualified as SAE. Six deaths (all infections) occurred during induction, corresponding to a 3.1% (6/194) death rate from immediate toxicity. Efficacy: Among 188 evaluable patients, complete responses (CR) were observed in 19.7%, nodular partial response (PR) in 2.7%, and PR in 73.9%, for an ORR of 96.3%, using stringent criteria. According to the updated guidelines of 2008 (Hallek), CR, CRi, and PR rates were 19.7%, 13.3%, and 63.3%, respectively. Conclusion: Four cycles of oral FC combined with 6 doses of R appear feasible in elderly patients with CLL; only 14% cannot receive the 4 courses and only 19% cannot proceed to randomization planned at day 90 post FCR4. Dose reduction and treatment interruption are unusual despite strict stopping criteria. Grade 3/4 neutropenia is frequent but rarely translates into serious infection. The response rate is high, and further analysis of MRD eradication is ongoing and will be presented. In conclusion, this approach could enable the safe administration of FCR to elderly fit CLL patients in first line. Long-term toxicity, occurring after randomization, will be scrutinized. Disclosures: Dartigeas: Roche: Consultancy. Van Den Neste:Roche: Consultancy. Leblond:Mundipharma: Honoraria; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria.
Published: 2012
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47. TP53 Mutation Profile and New Mutations in Chronic Lymphocytic Leukemia in Normandy

Author: Xavier Troussard, Seyeffedine Kadi, Stéphane Cheze, Jean-Pierre Vilque, Edouard Cornet, Nordine Lahyane, Dina Istasi, Vincent Launay, and Julien Alani
Subjects: Silent mutation, Oncology, medicine.medical_specialty, business.industry, Chronic lymphocytic leukemia, Immunology, Retrospective cohort study, Cell Biology, Hematology, Bioinformatics, medicine.disease, Biochemistry, Somatic evolution in cancer, Chemotherapy regimen, High Resolution Melt, Internal medicine, Medicine, Clinical significance, business, Trisomy
Abstract: Abstract 4593 Introduction: As deletion of 17p13 (del 17p13) in Chronic lymphocytic leukemia (CLL) patients is associated with poor outcome and chemorefractoriness to alkylating agents and purine analogues, current diagnostic guidelines recommend its screening at diagnosis and prior to treatment initiation. TP53 is a tumor suppressor gene, maps to 17p13 and is inactivated through somatic mutations or by 17p13 deletion. Recent studies show that TP53 mutation is of clinical relevance in CLL patients and has practical implication for therapeutic stratification. The purpose of this study is to characterize the TP53 mutation pattern and its incorporation into treatment algorithms in CLL patients treated in our center. Materials and methods: A retrospective study was performed on a cohort of 42 patients with CLL for whom clinical, biological and fluorescent in situ hybridization (FISH) data were available. Ages ranged from 31 to 88 (median, 63 years), 17 patients were in Binet stage A, 12 in B and 13 in stage C. Treatment was not in controlled trials, and standard clinical criteria were used for the initiation of therapy. DNA was extracted from 52 available samples and TP53 exons 2 to 11 were screened for mutations by high resolution melting (HRM) (Roche LC480). Mutations were confirmed by sequencing both strands using different primer sets (Beckman, Ceq 8000) then validated by the IARC and UMD TP53 Mutation Databases. Results: Out of 42 patients, del 17p13 was observed in 11 (26%), del 11q22 in 8 (19%), del 13q14 in 13 (31%), trisomy 12 in 2 (5%) and normal FISH in 20 (47.6%). We found an overall incidence of TP53 mutations of 19% (8 of 42 patients), 1 new mutation was identified and 5 mutations were not previously reported in CLL but in other cancers according to the IARC and UMD TP53 mutation Databases (table 1). A total of 65 polymorphisms were detected with a prevalence for the g.11446C>G polymorphism of 0.9 compared to 0.49 in published data. Amongst the 8 patients with TP53 mutations, 7 (87%) presented a 17p deletion and mutations were mainly located in the DNA binding domain (62%). 7 of 11 patients (63%) with 17p13 deletion harbored a TP53 mutation. In the absence of del 17p13 only 3% of patients (1 of 31) had a TP53 mutation (table 2). 5 of 8 patients with mutations (62%) presented with an advanced clinical stage and a median age of 56 years. Clonal evolution leading to acquisition of the TP53 mutation was not necessary related to therapy; 3 sequential samples were available for a patient with no abnormalities at diagnosis and who developed a TP53 mutation after 2 years and before therapy initiation. Another patient who was initially devoid of TP53 mutations and responded to treatment with standard chemotherapy, developed chemorefractoriness concomitant with a TP53 mutation acquisition. An interesting case was that of a patient who had been in complete remission after treatment with rituximab, fludarabin and cyclophosphamid (RFC) despite the presence of a TP53 mutation without del 17p13 at diagnosis. Sequencing demonstrated that this patient harbored a silent mutation in exon 4 g.12441C>G. In Conclusion: This study shows similar findings to published data except for a higher incidence of patients with TP53 mutations probably due to bias selection and a low cohort of patients. We identified a new mutation and 5 other mutations not previously detected in CLL patients. As TP53 is associated with poor outcome and chemorefractoriness, and its acquisition might be a result of positive pressure selection following treatment, we think it is of utmost importance to look for TP53 mutations in parallel to FISH at diagnosis and in case of chemorefractoriness using the HRM a cheap and sensitive method followed by sequencing positive cases. Disclosures: No relevant conflicts of interest to declare.
Published: 2011
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48. Prognostic Value of Early 18fluorodeoxyglucose PET Scan in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab Plus CHOP or High-Dose CHOP

Author: Taoufik El Gnaoui, Frédérique Kuhnowski, Christophe Fruchart, Jean-Pierre Vilque, Alain Rahmouni, Corinne Haioun, Stéphane Bardet, Emmanuel Itti, Chieh Lin, Michel Meignan, Karim Belhadj, and Jehan Dupuis
Subjects: business.industry, Immunology, Aggressive lymphoma, Cell Biology, Hematology, CHOP, medicine.disease, Biochemistry, Lymphoma, Log-rank test, International Prognostic Index, medicine, Rituximab, Nuclear medicine, business, Prospective cohort study, Diffuse large B-cell lymphoma, medicine.drug
Abstract: The results of 18Fluorodeoxyglucose – Positron Emission Tomography scan (PET) performed early during treatment (after 1 – 3 courses of chemotherapy) have been shown to predict outcome in aggressive lymphoma (Jerusalem, Haematologica 2000; Spaepen, Ann Oncol 2002; Haioun, Blood 2005). However, studies on early PET have been performed mostly in patients (pts.) treated without Rituximab. Our goal was to explore if the powerful predictive value of early PET was also observed in pts. treated with Rituximab-chemotherapy combinations. Seventy-three pts. with diffuse large B-cell lymphoma from 2 institutions were treated with R-CHOP (n=47) or R-high-dose CHOP (R-ACVBP, n=26) and were evaluated by PET after the two first cycles. PETs were interpreted on the basis of visual assessment. PET results were not taken into account to guide the treatment strategy after the 2 first cycles, which was solely based upon the results of conventional response assessment. Among responders, 16 young poor-risk pts. received planned consolidative high-dose therapy with autotransplant, while the others received immunochemotherapy based consolidation. Median age was 63 years (range 26–79) and 68% pts. were male. Baseline characteristics were as follows: Advanced Stage (Ann Arbor III–IV) 75%; Elevated LDH 62%; Poor performance status (ECOG 2–4) 32%. The International Prognostic Index was as follows: Low risk 27%, Low-intermediate 21%, Intermediate-high 21%, High risk 31%. PET was performed after a median of 15 days following the second cycle. Forty-nine pts. had a negative PET, while 24 were positive. With a median follow-up of 49 months, 11/49 (22%) PET negative pts. showed an event (progression or death) after a median delay of 13 months, while this was the case in 14/24 (58%) PET-positive patients after a median of 8 months. The estimated 5 year event free survival rates were 75% (95% CI: 63%–88%) for PET negative pts. and 41% (95% CI: 22%–61%) (log-rank test, p=0.001). Regarding overall survival, the estimated 5 year rates were 85% (95% CI: 78%–95%) and 53% (95% CI: 34%–74%) (log-rank test, p=0.005) in PET negative and PET positive pts., respectively. The same differences were found at 4 years when analysing separately pts. treated with R-CHOP and R-ACVBP (except for a non significant difference in OS in R-ACVBP pts.). In conclusion, we confirm the strong prognostic value of PET after 2 cycles in pts. treated with Rituximab combined to chemotherapy. Prospective studies (including a GELA study) are ongoing to evaluate the potential interest of tailoring treatment strategy to the results of early PET.
Published: 2008
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49. The VIP-ABVD Regimen Is Not Superior to the CHOP 21 for the Treatment of Non Epidermotropic Peripheral T Cell Lymphoma. Final Results of the 'LTP95' Protocol of the GOELAMS

Author: Charles Foussard, Olivier Tournilhac, Remy Gressin, Houchingue Eghbali, Bachera Choufi, Michel Peoc'h, Philippe Colombat, Philippe Quitet, Antoine Thyss, Bernard Desablens, Delphine Senecal, Vincent Delwail, Jean Pierre Vilque, Virginie Lucas, Jérôme Jaubert, Frédéric Maloisel, Bruno Richard, Noel-Jean Milpied, Françoise Huguet, Eric Deconinck, and Philippe Casassus
Subjects: medicine.medical_specialty, Ifosfamide, business.industry, Immunology, ABVD Regimen, VIP Regimen, Cell Biology, Hematology, CHOP, medicine.disease, Biochemistry, Gastroenterology, Peripheral T-cell lymphoma, Surgery, ABVD, Internal medicine, medicine, Stage (cooking), business, Etoposide, medicine.drug
Abstract: Introduction: There is non consensus today for the treatment of PTCL. The five years OS with the CHOP regimen is estimated to 40%. A five years OS of 65% have been expected with an alternating VIP/ABVD regimen in a cohort ot 58 patients (pts) retrospectively studied by the same institution in Grenoble FRANCE (results presented at the french haematology society in 2000). Aim of the study and methods: To confirm the superiority of the VIP/ABVD in first line for pts with PTCL. We have compared the 2 years EFS of pts receiving 8x CHOP21 or 6 alternating VIP/ABVD in a random manner. The VIP/ABVD regimen consisted of an alternance of three VIP regimen (VP16 100 mg/sqm D1 to D3; Ifosfamide 1000 mg/sqm D1 to D5 and Cisplatinum 20 mg/sqm D1 to D5) and three ABVD (Adriblastin 50 mg/sqm, Bleomycin 10 mg/sqm, Vinblastin 10 mg/sqm and Deticene 375 mg/sqm D1 and D14). A 40 grays IF irradiation was systematically used for AA stage I-II and on the tumoral sites larger than 5 cm to complete the treatment plan. Results: 100 pts were included and 88 retained after a centralized pathologic review. 57 pts were diagnosed as PTCLu, 15 LAI, 10 T and 4 NTNB anaplasic, 1 angiocentric and 1 NK type. 45 pts received the CHOP and 43 the VIP/ABVD. 53/88 pts (60%) achieved a CR (34) or PR>75% (19). With a median Fup of 26.5 months EFS and OS are respectively 40% at 2 years and 40% at 4 y. There is no difference between the two groups. Two factors but not the IPI score have significantly influenced the survivals: histologic types (anaplasic vs no anaplasic) and AA stage (I–II vs III–IV). Conclusion: The VIP/ABVD is not superior to the CHOP regimen for the treatment of PTCL. The combination Ann Arbor stage and the histologic pattern is the best predictive factor of the survivals. New innovative approach are mandatory to improve the prognostic of PTCL.
Published: 2006
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50. Granulocyte Colony-Stimulating Factor After Intensive Consolidation Chemotherapy in Acute Myeloid Leukemia: Results of a Randomized Trial of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques

Author: JF Abgrall, François Guilhot, Eric Solary, Martine Delain, Denis Guyotat, Brigitte Witz, J-L Harousseau, Olivier Tournilhac, E. Deconinck, Bruno Lioure, Bruno Audhuy, Philippe Casassus, Mathilde Hunault-Berger, Jean-Pierre Vilque, Bernard Desablens, and P.Y. Le Prise
Subjects: Adult, Amsacrine, Male, Antimetabolites, Antineoplastic, Cancer Research, medicine.medical_specialty, Neutropenia, Adolescent, Filgrastim, Antineoplastic Agents, Gastroenterology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, medicine, Humans, Etoposide, Mitoxantrone, business.industry, Remission Induction, Cytarabine, Myeloid leukemia, Consolidation Chemotherapy, Length of Stay, Middle Aged, medicine.disease, Antineoplastic Agents, Phytogenic, Recombinant Proteins, Anti-Bacterial Agents, Surgery, Granulocyte colony-stimulating factor, Hospitalization, Treatment Outcome, Oncology, Leukemia, Myeloid, Acute Disease, Female, business, medicine.drug
Abstract: PURPOSE: Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR). PATIENTS AND METHODS: One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 μg/kg. RESULTS: In the G-CSF group, the median duration of neutropenia (< 0.5 × 109/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P < .001) and after ICC 2 (20 v 28 days, P < .001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P < .001; 29 v 34 days after ICC 2, P < .001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm. CONCLUSION: G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.
Published: 2000
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