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1. Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Author

Hervé Tilly, Hélène Lanic, Romain Modzelewski, Florian Clatot, Jean Michel Picquenot, Sylvain Mareschal, Jerôme Kraut-Tauzia, Fabrice Jardin, Aspasia Stamatoullas, Stéphane Leprêtre, Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), 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), Breton, Céline, Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), service d'anatomo-pathologie, CRLCC Henri Becquerel, Equipe Quantification en Imagerie Fonctionnelle ( QuantIF-LITIS ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ) -Université Le Havre Normandie ( ULH ), Normandie Université ( NU ), 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 ), and CRLCC Haute Normandie-CRLCC Henri Becquerel

Subjects
Male, Sarcopenia, MESH : Retrospective Studies, MESH : Antineoplastic Combined Chemotherapy Protocols, Body Surface Area, MESH : Aged, Gastroenterology, Body Mass Index, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH : Muscle, Skeletal, MESH: Sarcopenia, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, Aged, 80 and over, 0303 health sciences, education.field_of_study, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, Vincristine, 030220 oncology & carcinogenesis, Rituximab, MESH : Vincristine, medicine.medical_specialty, Tomography Scanners, X-Ray Computed, MESH : Tomography Scanners, X-Ray Computed, MESH: Prognosis, MESH: Body Mass Index, MESH: Doxorubicin, 03 medical and health sciences, Humans, MESH : Aged, 80 and over, education, Cyclophosphamide, Aged, Retrospective Studies, MESH: Age Factors, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH : Humans, MESH : Prednisone, MESH: Cyclophosphamide, MESH: Retrospective Studies, MESH : Organ Size, medicine.disease, MESH : Body Mass Index, MESH : Sarcopenia, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Prednisone, MESH: Female, Body mass index, Diffuse large B-cell lymphoma, Cancer Research, MESH: Organ Size, [SDV]Life Sciences [q-bio], MESH : Lymphoma, Large B-Cell, Diffuse, Antibodies, Monoclonal, Murine-Derived, MESH: Aged, 80 and over, MESH: Body Surface Area, International Prognostic Index, Prednisone, hemic and lymphatic diseases, MESH : Female, MESH : Cyclophosphamide, MESH: Aged, Body surface area, MESH: Muscle, Skeletal, MESH : Prognosis, Age Factors, Hematology, Organ Size, Treatment Outcome, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, MESH : Body Surface Area, MESH : Male, Population, MESH: Vincristine, MESH : Treatment Outcome, Internal medicine, medicine, MESH : Doxorubicin, Muscle, Skeletal, 030304 developmental biology, MESH: Tomography Scanners, X-Ray Computed, business.industry, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Surgery, Doxorubicin, MESH: Lymphoma, Large B-Cell, Diffuse, MESH : Age Factors, business
Abstract

International audience; Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.

Published
2013

2. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up

Author

Gilles Salles, Philippe Colombat, Charles Foussard, Franck Morschhauser, F. Lazreg, Pierre Soubeyran, Corinne Haioun, Vincent Delwail, Nicole Brousse, Catherine Sebban, Pauline Brice, Philippe Solal-Celigny, Hervé Tilly, Catherine Thieblemont, Loïc Bergougnoux, Eric Deconinck, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hématologie, Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Service d'Oncologie Médicale, Centre Léon Bérard [Lyon], Service d'oncologie, CRLCC Henri Becquerel, Service d'Hématologie, Roche, Onco-radiothérapie, hématologie, Centre Jean Bernard, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Angers-Hôtel Dieu, and Saas, Philippe

Subjects
Male, MESH : Immunization, Passive, MESH : Induction Chemotherapy, Follicular lymphoma, Kaplan-Meier Estimate, Gastroenterology, Antibodies, Monoclonal, Murine-Derived, MESH: Lymphoma, Follicular, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Lymphoma, Follicular, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, MESH : Neoplasm Recurrence, Local, Induction Chemotherapy, Hematology, MESH: Follow-Up Studies, MESH : Adult, Middle Aged, MESH: Induction Chemotherapy, 3. Good health, MESH : Antineoplastic Agents, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, MESH: Immunization, Passive, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Population, Antineoplastic Agents, MESH : Treatment Outcome, Disease-Free Survival, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH : Middle Aged, Progression-free survival, education, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, MESH : Lymphoma, Follicular, MESH : Humans, Immunization, Passive, Induction chemotherapy, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Lymphoma, Surgery, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, MESH: Female, Progressive disease, Follow-Up Studies, 030215 immunology
Abstract

International audience; BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.

Published
2012
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3. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey

Author

Antoine Huart, Estibaliz Lazaro, P. Belenotti, Olivier Hermine, David Launay, Guillaume Le Guenno, Thierry Zenone, Adeline Lacraz, Patrice Cacoub, Evguenia Krastinova, Franck Bridoux, Patricia Senet, P. Rullier, Elisabeth Diot, Xavier Mariette, Luc de Saint-Martin, Thomas Quemeneur, Isabelle Marie, Emmanuelle Plaisier, Benjamin Terrier, Fabrice Carrat, Fabrice Bonnet, Olivier Hinschberger, Jean-Emmanuel Kahn, Jean-Marc Léger, Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Médecine Interne (MARSEILLE - Med Int), Assistance Publique - Hôpitaux de Marseille (APHM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Médecine Interne (VALENCIENNES - Med Int), CH Valenciennes, Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire Estaing, CHU Estaing, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service de Médecine Interne B, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Médecine Interne, Hôpital Bretonneau, Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Médecine Interne (VALENCE - Med Int), Centre hospitalier de Valence, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Remodelage et Reparation du Tissu Renal, Service de médecine interne [CHU Pitié-Salpétrière], Biologie et thérapeutique des pathologies immunitaires (BTPI), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Médecine Interne ( MARSEILLE - Med Int ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Département de Médecine Interne ( VALENCIENNES - Med Int ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire d'Immunologie ( EA 2686 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Médecine Interne ( VALENCE - Med Int ), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Biologie et thérapeutique des pathologies immunitaires ( BTPI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université de Brest (UBO)-Université de Brest (UBO), CHU Clermont-Ferrand, Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [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), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [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), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)

Subjects
Male, MESH: Combined Modality Therapy, MESH : Retrospective Studies, [SDV]Life Sciences [q-bio], MESH : Aged, Arthritis, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, MESH: Antibodies, Monoclonal, Cohort Studies, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, MESH : Female, MESH: Data Collection, MESH: Cohort Studies, MESH : Algorithms, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Data Collection, MESH: Vasculitis, Antibodies, Monoclonal, Hematology, Middle Aged, Connective tissue disease, Combined Modality Therapy, 3. Good health, MESH : Vasculitis, MESH : Infection, Treatment Outcome, Cryoglobulinemia, MESH : Antibodies, Monoclonal, Rituximab, Female, medicine.symptom, MESH : Data Collection, Vasculitis, MESH: Infection, Algorithms, medicine.drug, medicine.medical_specialty, MESH: Cryoglobulinemia, MESH : Male, Immunology, MESH : Cohort Studies, MESH: Algorithms, MESH : Treatment Outcome, Infections, MESH : Adrenal Cortex Hormones, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH : Middle Aged, Aged, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH: Retrospective Studies, Cell Biology, Skin ulcer, medicine.disease, MESH : Cryoglobulinemia, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Regimen, Peripheral neuropathy, MESH: Antibodies, Monoclonal, Murine-Derived, business, MESH : Combined Modality Therapy, MESH: Female
Abstract

Data on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials.

Published
2012
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4. A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor

Author

Stéphanie Brayer, Philippe Le Bouteiller, Nabila Jabrane-Ferrat, Fabienne Meggetto, Armand Bensussan, Salem Chouaib, Julie Tabiasco, Jean Kadouche, Olivier Chose, Maryse Aguerre-Girr, Muhammad Zaeem Noman, Sylvie Giuriato, Muriel Golzio, Sophie Chabot, Karine Bigot, Stéphane Galiacy, François Malecaze, Jérôme Giustiniani, Alexandra C. Provost, Jean-Philippe Jais, Elisabeth Bellard, Marc Abitbol, Justin Teissié, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'étude et de recherche thérapeutiques en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie [Hopital Purpan - Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Department of Cell Biology (DUMC), Duke University Medical Center, MAT Biopharma, MAT Ltd., Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Sciences et Technologies du Medicament de Toulouse Toulouse, France. (UMR2587, CNRS-PIERRE FABRE), PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Fonctions Cellulaires et Moleculaires de l'Appareil Respiratoire et des Vaisseaux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de recherche biomédicale (IMRB), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut de pharmacologie et de biologie structurale ( IPBS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Cell Biology ( DUMC ), Oncodermatologie, immunologie et cellules souches cutanées ( DIO U976 ), and Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Pathology, MESH : Retinal Diseases, MESH : Antineoplastic Combined Chemotherapy Protocols, Angiogenesis, MESH: Rabbits, Fibroblast growth factor, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Neovascularization, Antibodies, Monoclonal, Murine-Derived, Mice, MESH : Fibroblast Growth Factor 2, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH : Receptors, Immunologic, Immunology and Allergy, MESH : Female, MESH: Animals, Receptors, Immunologic, Melanoma, MESH: Antigens, CD, MESH : Cyclophosphamide, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, 0303 health sciences, Neovascularization, Pathologic, MESH : Mice, Nude, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Colonic Neoplasms, MESH : Corneal Neovascularization, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fibroblast Growth Factor 2, Rabbits, MESH : GPI-Linked Proteins, medicine.symptom, Intravital microscopy, Retinopathy, medicine.medical_specialty, MESH: Melanoma, MESH : Male, Immunology, MESH : Melanoma, MESH: Mice, Inbred BALB C, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, GPI-Linked Proteins, Article, 03 medical and health sciences, Retinal Diseases, Antigens, CD, Cell surface receptor, MESH : Mice, MESH : Antigens, CD, medicine, MESH: Mice, Nude, Animals, Humans, Corneal Neovascularization, MESH : Rabbits, Cyclophosphamide, MESH: Mice, MESH: Receptors, Immunologic, MESH : Mice, Inbred BALB C, MESH: Retinal Diseases, 030304 developmental biology, MESH: Colonic Neoplasms, MESH: Humans, MESH: Corneal Neovascularization, MESH: Fibroblast Growth Factor 2, MESH : Humans, MESH : Neovascularization, Pathologic, MESH: Cyclophosphamide, medicine.disease, eye diseases, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, MESH: Antibodies, Monoclonal, Murine-Derived, Corneal neovascularization, MESH : Animals, MESH: GPI-Linked Proteins, MESH: Neovascularization, Pathologic, MESH: Female
Abstract

A monoclonal anti-CD160 antibody inhibits the growth of new vessels in pathological ocular and tumor neoangiogenesis but not in healthy tissues., Angiogenesis plays an essential role in several diseases of the eye and in the growth of solid tumors, but existing antiangiogenic therapies have limited benefits in several cases. We report the antiangiogenic effects of a monoclonal antibody, CL1-R2, in several animal models of neovascularization. CL1-R2 recognizes human CD160, a membrane receptor which is conserved in various mammal species. We show that CD160 is expressed on the endothelial cells of newly formed blood vessels in human colon carcinoma and mouse B16 melanoma but not in vessels of healthy tissues. CL1-R2 reduced fibroblast growth factor 2–induced neovascularization in the rabbit cornea, in a mouse model of oxygen-induced retinopathy, and in a mouse Matrigel plug assay. Treatment of B16 melanoma-bearing mice with CL1-R2 combined with cyclophosphamide chemotherapy caused regression of the tumor vasculature and normalization of the remaining vessels as shown by Doppler ultrasonography, intravital microscopy, and histology. These studies validate CD160 as a potential new target in cases of human pathological ocular and tumor neoangiogenesis that do not respond or become resistant to existing antiangiogenic drugs.

Published
2011
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5. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101

Author

Stéphanie Herveau, Stéphane Dalle, Pablo Umana, Lina Reslan, Timothee Besseyre de Horts, Frank Herting, Thomas Friess, Charles Dumontet, Christian Klein, Adriana Plesa, Equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hematology Laboratory, Hospices Civils de Lyon, Institut de Mathématiques de Bourgogne [Dijon] (IMB), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Mathématiques de Bourgogne [Dijon] ( IMB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre de Recherche en Cancérologie de Lyon ( CRCL )

Subjects
Cancer Research, Follicular lymphoma, MESH: Antigens, CD20, Mice, SCID, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Mice, MESH: Lymphoma, Follicular, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, MESH : Female, MESH: Animals, MESH: Mice, SCID, Cytotoxicity, Lymphoma, Follicular, MESH : Cyclophosphamide, CD20, 0303 health sciences, Antibodies, Monoclonal, 3. Good health, Oncology, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, Monoclonal, Rituximab, Female, Antibody, MESH: Dose-Response Relationship, Immunologic, medicine.drug, MESH: Xenograft Model Antitumor Assays, MESH: Cell Line, Tumor, medicine.drug_class, Dose-Response Relationship, Immunologic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH : Xenograft Model Antitumor Assays, Monoclonal antibody, Antibodies, Monoclonal, Humanized, MESH : Antibodies, Monoclonal, Humanized, 03 medical and health sciences, MESH: Gene Expression Profiling, Antigen, MESH : Antigens, CD20, Cell Line, Tumor, MESH : Mice, medicine, Animals, Humans, Cyclophosphamide, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH : Cell Line, Tumor, Gene Expression Profiling, MESH : Lymphoma, Follicular, MESH : Gene Expression Profiling, MESH : Humans, MESH: Cyclophosphamide, medicine.disease, Antigens, CD20, Xenograft Model Antitumor Assays, MESH : Mice, SCID, MESH : Antibodies, Monoclonal, Murine-Derived, MESH : Dose-Response Relationship, Immunologic, MESH: Antibodies, Monoclonal, Humanized, MESH: Antibodies, Monoclonal, Murine-Derived, biology.protein, MESH : Animals, MESH: Female
Abstract

GA101 is a novel glycoengineered Type II CD20 monoclonal antibody. When compared with rituximab, it mediates less complement-dependent cytotoxicity (CDC). As expected for a Type II antibody, GA101 appears not to act through CDC and is more potent than the Type I antibody rituximab in inducing cell death via nonclassical induction of apoptosis cytotoxicity, with more direct cytotoxicity and more antibody-dependent cell-mediated cytotoxicity. We evaluated the antitumor activity of GA101 against the human-transformed follicular lymphoma RL model in vivo in severe combined immunodeficient mice (SCID) mice. GA101 induced stronger inhibition of tumor growth than rituximab. Combination of GA101 with cyclophosphamide in vivo confirmed the superiority of GA101 over rituximab. Neutralizing the complement system with cobra venom factor partially impaired the antitumor activity of rituximab, but had no impact on the efficacy of GA101. In vitro GA101 more potently induced cell death of RL cells than rituximab. The expression of a limited number of genes was found to be induced by both antibodies after exposure in vitro. Among these, early growth response 1 and activation transcription factor 3 were confirmed to be increased at the protein level, suggesting a possible role of these proteins in the apoptotic signalling of anti-CD20 antibodies. These data imply that GA101 is superior to rituximab not only as a single agent, but also in combination with chemotherapy. These data suggest the presence of novel signalization pathways activated after exposure to anti-CD20 antibodies. Mol Cancer Ther; 10(1); 178–85. ©2011 AACR.

Published
2011
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6. Effects of rituximab therapy on quality of life in patients with primary Sjögren's syndrome

Author

Devauchelle-Pensec V, Morvan J, Ac, Rat, Jousse-Joulin S, Pennec Y, Jo, Pers, Jamin C, Yves Renaudineau, Quintin-Roué I, Cochener B, Youinou P, Saraux A, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Rhumatologie [CHRU Nancy], Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Hôpital Morvan [Brest], CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Université de Brest (UBO), Service d'ophtalmologie [Brest], Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lorraine (UL), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Laboratoire de dynamique et structures des matériaux moléculaires (LDSMM), Université de Lille, Sciences et Technologies-Université du Littoral Côte d'Opale-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie et Immunothérapie, Laboratoire de Traitement de l'Information Medicale (LaTIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Unite mixte de recherche en droit comparé (UMRDC), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] ( Pôle S2R ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 ( IEMN ), Ecole Centrale de Lille-Institut supérieur de l'électronique et du nunérique (ISEN)-Université de Valenciennes et du Hainaut-Cambresis ( UVHC ) -Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Unite mixte de recherche en droit comparé ( UMRDC ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), CHRU Brest - Laboratoire d'Anatomo-Pathologie ( CHU - AnaPath ), Université de Brest ( UBO ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), and Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, MESH: Antirheumatic Agents, Health Status, Severity of Illness Index, Antibodies, Monoclonal, Murine-Derived, hemic and lymphatic diseases, Surveys and Questionnaires, MESH : Female, MESH: Health Status, MESH: Treatment Outcome, MESH: Middle Aged, MESH : Questionnaires, MESH : Adult, Middle Aged, MESH : Antirheumatic Agents, humanities, Sjogren's Syndrome, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Young Adult, Antirheumatic Agents, MESH : Severity of Illness Index, Female, MESH: Rituximab, MESH: Pain, Rituximab, MESH : Pain, Adult, Adolescent, MESH : Male, MESH : Young Adult, Pain, MESH : Treatment Outcome, Young Adult, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH: Severity of Illness Index, Humans, MESH : Middle Aged, MESH : Health Status, MESH: Surveys and Questionnaires, MESH: Adolescent, MESH: Humans, MESH: Questionnaires, MESH : Humans, MESH: Quality of Life, MESH: Adult, MESH : Quality of Life, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, stomatognathic diseases, MESH: Sjogren's Syndrome, MESH: Antibodies, Monoclonal, Murine-Derived, Quality of Life, MESH : Sjogren's Syndrome, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; OBJECTIVES: To assess the efficacy of the anti-CD20 antibody rituximab in improving physical function and health-related quality of life (HRQoL) in patients with active primary Sjögren's syndrome (pSS), as well as the duration and sources of HRQoL improvements. METHODS: Sixteen patients with pSS received rituximab infusions (375 mg/m2) at weeks 0 and 1 and were followed up for 36 weeks. All patients fulfilled 2002 American-European Consensus Group criteria for pSS and had active disease defined as scores >50 mm on two of four 100-mm visual analogue scales (VAS) evaluating global disease activity, fatigue, pain, and dryness. Standardised evaluations including the Short Form 36 Health Survey (SF-36) were conducted. SF-36 score changes from baseline to weeks 12, 24, and 36 were assessed. RESULTS: Baseline mean SF-36 scores were considerably decreased, compared to the general same-age population. Role-physical (14.1 ± 27.4), role-emotional (12.5 ± 29.9), vitality (26.2 ± 14.3), and general health (32.6 ± 11.2) were the dimensions with the worst scores. Twelve weeks after rituximab, the mental component summary score was improved in 15 patients (mean improvement, 31.2 ± 36.4, p=0.001) and the physical component summary score in 14 patients (mean improvement, 16.9 ± 26.2, p=0.049). Further improvements occurred from week 12 to week 24, and most of the gains were sustained at week 36. Improvements in the physical and mental component summary scores failed to correlate with improvements in the VAS scores. CONCLUSIONS: Substantial alterations in HRQoL were noted in patients with pSS. Rituximab infusions without corticosteroid therapy produced meaningful improvements in HRQoL. Controlled studies of rituximab are needed.

Published
2010

7. Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study

Author

Copie-Bergman, Christiane, Gaulard, Philippe, Leroy, Karen, Briere, Josette, Baia, Maryse, Jais, Jean-Philippe, Salles, Gilles, Berger, Françoise, Haioun, Corinne, Tilly, Herve, Emile, Jean-François, Banham, Alison, Mounier, Nicolas, Gisselbrecht, Christian, Feugier, Pierre, Coiffier, Bertrand, Molina, Thierry, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Département de pathologie, Hospices Civils de Lyon ( HCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'Hématologie, CRLCC Henri Becquerel, Service d'anatomie pathologique, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Nuffield Department of Clinical Laboratory Sciences, University of Oxford [Oxford], Service d'onco-hématologie, CHU Nice-Hôpital l'Archet, Service d'hématologie-oncologie adultes, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ), This study was supported by a grant from the Programme Hospitalier de Recherche Clinique AP-HP (AOM 03060), Dako A/S and ARTGIL (Association pour la Recherche Thérapeutique, Génétique et Immunologique dans les lymphomes). AHB was supported by Leukaemia Research, UK., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'anatomie pathologique [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
MESH : Antineoplastic Combined Chemotherapy Protocols, MESH : Aged, MESH : Dose-Response Relationship, Drug, MESH: Risk Assessment, MESH : Lymphoma, Large B-Cell, Diffuse, MESH: Antibodies, Monoclonal, MESH: Dose-Response Relationship, Drug, MESH : Proto-Oncogene Proteins c-bcl-2, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, immune system diseases, hemic and lymphatic diseases, MESH : Female, MESH: In Situ Hybridization, Fluorescence, MESH : Risk Assessment, MESH : Cyclophosphamide, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, MESH : Prognosis, MESH: Enzyme-Linked Immunosorbent Assay, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Predictive Value of Tests, MESH : In Situ Hybridization, Fluorescence, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Genes, myc, MESH: Survival Analysis, MESH : Antibodies, Monoclonal, MESH : Severity of Illness Index, MESH : Vincristine, MESH: Probability, MESH : Probability, MESH : Male, MESH : Drug Administration Schedule, MESH: Vincristine, MESH : Treatment Outcome, MESH: Drug Administration Schedule, MESH: Multivariate Analysis, MESH: Prognosis, MESH: Doxorubicin, MESH: Severity of Illness Index, MESH : Doxorubicin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Aged, 80 and over, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Genes, myc, MESH: Humans, MESH : Humans, MESH: Biological Markers, MESH: Cyclophosphamide, MESH : Multivariate Analysis, MESH : Prednisone, MESH : Proportional Hazards Models, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, MESH : Biological Markers, MESH: Proto-Oncogene Proteins c-bcl-2, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Lymphoma, Large B-Cell, Diffuse, MESH : Survival Analysis, MESH: Prednisone, MESH: Female
Abstract

International audience; PURPOSE: To evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Patients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray. RESULTS: LMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis. CONCLUSION: Our study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.

Published
2009
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