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101. 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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102. The regulatory capacity of B cells directs the aggressiveness of CLL

Author: Sophie Hillion, Audrey Mohr, Hussam Saad, Yves Renaudineau, Christophe Jamin, Christelle Le Dantec, Marie Cumin, Jacques-Olivier Pers, Cristina Bagacean, Pierre Pochard, Adrian Tempescul, Anne Bordron, and Christian Berthou
Subjects: 0301 basic medicine, tlr9, lcsh:Immunologic diseases. Allergy, Lymphocytosis, T cell, Chronic lymphocytic leukemia, Immunology, Biology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, b cells, Receptor, B cell, cll, Original Research, TLR9, aggressiveness, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, regulatory capacity, medicine.symptom, lcsh:RC581-607
Abstract: Chronic lymphocytic leukemia (CLL) is associated with abnormal T-cell responses responsible for defective anti-tumor activities. Intriguingly, CLL B cells share phenotypical characteristics with regulatory B (Breg) cells suggesting that they might negatively control the T-cell activation and immune responses. We elaborated an in vitro co-culture system with T cells to evaluate the Breg capacities of CLL B cells following innate Toll-like receptor 9 (TLR9) engagement. We demonstrated that B cells from half of the patients exhibited regulatory capacities, whilst B cells from the remaining patients were unable to develop a Breg function. The T cell sensitivities of all patients were normal suggesting that defective Breg activities were due to intrinsic CLL B cell deficiencies. Thus, TLR-dedicated gene assays highlighted differential signature of the TLR9 negative regulation pathway between the two groups of patients. Furthermore, correlations of the doubling time of lymphocytosis, the time to first treatment, the mutational status of IgVH and the Breg functions indicate that patients with efficient Breg activities have more aggressive CLL than patients with defective Breg cells. Our in vitro observations may open new approaches for adjusting therapeutic strategies targeting the Breg along with the evolution of the disease.
Published: 2018

103. Superiority of Allogenic Stem Cell Transplantation after Anti-PD1 Therapy over Anti-PD1 Monotherapy Alone in Relapse/Refractory Hodgkin Lymphoma Real World Evidence from the French Early Access Program

Author: Emmanuelle Nicolas-Virelizier, Remy Dulery, Adrien Chauchet, Roch Houot, Jean Marc Schiano de Collela, Herv Ghesquieres, Guillaume Manson, Anna Schmitt, Alain Delmer, Aspasia Stamatoullas, Jean-Baptiste Mear, Cécile Borel, Charles Herbaux, Georges Garnier, Rene-Olivier Casasnovas, Marie-Pierre Moles, Krimo Bouabdallah, Adrian Tempescul, Pauline Brice, Laurent Dercle, Lysiane Molina, Bénédicte Deau-Fisher, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CRLCC Centre Paoli - Calmettes [Marseille], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], CHU Grenoble, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hopital Saint-Louis [AP-HP] (AP-HP), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Real world evidence, Biochemistry, 3. Good health, Transplantation, 03 medical and health sciences, 030104 developmental biology, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Stem cell, Anti pd1, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Figure 1). At the time of transplantation, 8 patients were in CR, 5 in partial response (PR) and 4 had progressed of whom 3 received a salvage therapy before alloHSCT. Interestingly, 6 out of 7 patients who were not in CR at the time of transplantation (5 PR and 1 progressive disease) converted into a CR after alloHSCT. At the time of analysis, 14 patients were alive and 13 remained disease-free after a median follow-up of 30.4 months. One-year OS and PFS from alloHSCT were 82% and 76%, respectively. Among responding patients (i.e. in CR or PR) after nivolumab monotherapy, those who underwent subsequent alloHSCT (N=13) had a better outcome than those who were not consolidated with alloHSCT (N=35) (Figure 2). In the transplanted group, none of the patients relapsed whereas in the non-transplanted group 60% of the patients relapsed (p Conclusions: Although patients who achieve a CR upon anti-PD1 therapy may experience prolonged remissions, most R/R HL patients treated with anti-PD1 antibody eventually progress or relapse. Our study demonstrates unprecedented disease-free survival in patients undergoing consolidation with alloHSCT after anti-PD1 therapy. Interestingly, alloHSCT post anti-PD1 can convert incomplete responses into CR in most cases. Despite expected toxicities, alloHSCT after anti-PD1 therapy appears manageable and safe in most patients. Our results suggest that consolidation with alloHSCT may represent a good option in patients treated with anti-PD1, notably in patients who are unable to achieve a CR. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Brice:bristol myers squibb: Consultancy, Honoraria. Houot:bristol myers squibb: Consultancy, Honoraria.
Published: 2018
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104. Nouvelles voies thérapeutiques dans la LLC

Author: Renaudineau, Yves, Tempescul, Adrian, Levy, Vincent, Laboratoire d'Immunologie et Immunothérapie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), 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), Hôpital Avicenne [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

105. Resistance to complement activation, cell membrane hypersialylation and relapses in chronic lymphocytic leukemia patients treated with rituximab and chemotherapy

Author: Bordron, Anne, Bagacean, Cristina, Mohr, Audrey, Tempescul, Adrian, Bendaoud, Boutahar, Deshayes, Stéphanie, Dalbies, Florence, Buors, Caroline, Saad, Hussam, Berthou, Christian, Pers, Jacques-Olivier, Renaudineau, Yves, 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), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Laboratoire d'hématologie (Labo Hémato - BREST), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: sialylation, rituximab, hemic and lymphatic diseases, [SDV]Life Sciences [q-bio], chronic lymphocytic leukemia, complement-dependent cytotoxicity, progression-free survival, ComputingMilieux_MISCELLANEOUS, Research Paper
Abstract: The anti-CD20-specific monoclonal antibody rituximab (RTX), in combination with chemotherapy, is commonly used for primary treatment in chronic lymphocytic leukemia (CLL). However, relapses remain important and activation of the complement pathway is one of the mechanisms by which RTX generates the destruction of B cells directly by complement-dependent cytotoxicity (CDC), or indirectly by antibody-dependent cellular phagocytosis. In this study, the RTX capacity to induce CDC was established in 69 untreated CLL patients, this cohort including 34 patients tested before the initiation of RTX-chemotherapy. In vitro CDC-resistance to RTX predicts lower response rates to RTX-chemotherapy and shorter treatment free survival. Furthermore, the predictive value of CDC-resistance was independent from the clinical, cytogenetic and FcγR3A V158F polymorphism status. In contrast, CLL cell resistance to CDC predominates in IGHV unmutated patients and was related to an important α2-6 sialyl transferase activity, which in turn increases cell surface α2-6 hypersialylation. Suspected factors associated with resistance to CDC (CD20, CD55, CD59, factor H, GM1, and sphingomyelin) were not differentially expressed or recruited between the two CLL groups. Altogether, results provide evidence that testing RTX capacity to induce CDC in vitro represents an independent predictive factor of therapeutic effects of RTX, and that α2-6 hypersialylation in CLL cells controls RTX response through the control of the complement pathway. At a time when CLL therapy is moving towards chemo-free treatments, further experiments are required to determine whether performing an initial in vitro assay to appreciate CLL CDC resistance might be useful to select patients.
Published: 2018
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106. Distinct Mechanisms of Alterations in DNA Methylation/Demethylation Leading to Myelodysplastic Syndromes/Acute Myeloid Leukemia and Chronic Lymphocytic Leukemia

Author: Wesley H. Brooks, Jean Christophe Ianotto, Cristina Bagacean, Adrian Tempescul, Mihnea Zdrenghea, Anne Bordron, Yves Renaudineau, Marie-Anne Couturier, Christian Berthou, Gaelle Guillerm, Lymphocyte B et Auto-immunité (LBAI), 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Immunologie et Immunothérapie [Brest], Department of Chemistry, University of South Florida, Tampa, FL, USA., University of South Florida [Tampa] (USF), Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Laboratoire d'Immunologie et Immunothérapie, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 0303 health sciences, Myeloid, Myelodysplastic syndromes, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Myeloid leukemia, Biology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Leukemia, 0302 clinical medicine, medicine.anatomical_structure, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, DNA methylation, medicine, Cancer research, Epigenetics, CD5, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Myelodysplastic syndromes (MDS) represent malignant myeloid disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased risk of progression to acute myeloid leukemia (AML). AML is a highly heterogeneous disease characterized by the presence of large chromosomal translocations, gene fusions as well as mutations in the genes involved in hematopoietic proliferation and differentiation resulting in the accumulation of poorly differentiated myeloid cells. Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia, and is characterized by the clonal proliferation and accumulation of mature, long-lived CD5+ B cells. Epigenetic dysregulations are present in both myeloid disorders and in CLL, but, in contrast to MDS and AML that present gene fusions (TET1/LCX) and somatic mutations in epigenetic regulators (DNMT3A, TET2, IDH1/2), in CLL, epigenetic modifications are not qualitative but mostly quantitative (DNMT3A, TET2) and associated with disease progression. As a consequence, in MDS, AML and CLL, the focal or global DNA methylation/demethylation process is altered. In conclusion, a better qualitative and quantitative understanding of epigenetic regulators during myeloid/lymphoid differentiation, their localization and the co-recruitment of other proteins at specific DNA target sites, could offer us the possibility to modulate hematopoiesis, restore the initial balance, and control disease progression.
Published: 2018
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107. Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial

Author: Judith Trotman, Sally F Barrington, David Belada, Michel Meignan, Robert MacEwan, Carolyn Owen, Václav Ptáčník, András Rosta, Günter R Fingerle-Rowson, Jiawen Zhu, Tina Nielsen, Deniz Sahin, Wolfgang Hiddemann, Robert E Marcus, Andrew Davies, Mark Hertzberg, Andrew Grigg, Paul Cannell, Hang Quach, Stephen Opat, Constantine Tam, Paula Marlton, Ann Janssens, Fritz Offner, Koen Van eygen, Randeep Sangha, Pam Mckay, Jonathan Wilson, Richard Van Der Jagt, Daryl Roitman, Marek Trneny, Jiri Mayer, Katell Le Du, Philippe Solal-Celigny, Guillaume Cartron, Charles Foussard, Norbert Frickhofen, Peter Schmidt, Ullrich Graeven, Tobias Gaska, Rudolf Schlag, Martin Sökler, Gabriele Prange-Krex, Axel Florschütz, Hans-Walter Lindemann, Christoph Schimmelpfennig, Solveig Tonndorf, Mathias Hänel, Georg Hess, Enrico Schalk, Heiko Hütten, Gottfried Doelken, Michael Pfreundschuh, Ulrich Keller, Michael Herold, Roswitha Forstpointner, Ursula Vehling-Kaiser, Martin Hoffmann, Zita Borbenyi, Miklos Udvardy, Judit Demeter, Alessandro Rambaldi, Enrica Morra, Federico Massimo, Ignazio Majolino, Monica Balzarotti, Gianpietro Semenzato, Miguel Angel Canales Albendea, Francisco Javier Peñalver Parraga, Alfonso Soler Campos, Juan Manuel Sancho Cia, Jose Antonio Marquez Navarro, Carlos Grande Garcia, Herman Nilsson-Ehle, Helen Mccarthy, Chris Pocock, Shalal Sadullah, Ram Malladi, John Radford, Ed Kanfer, Anton Kruger, Dominic Culligan, Martin Dyer, Ruth Pettengell, John Seymour, John Gribben, Saad Al-Ismail, Faris Al-Refaie, Norbert Blesing, Christopher Macnamara, Ann O'callaghan, Andrew Haynes, George Follows, Roderick Johnson, David Cunningham, Kristian Bowles, Graham Collins, Eve Gallop-Evans, Stephen Robinson, Chezhian Subash, James Bailey, Viran Holden, Jeffrey Neidhart, Moacyr De Oliveira, Haluk Tezcan, Kevin Kim, Suman Kambhampati, Keith Lanier, John Mcclean, Kensei Tobinai, Kiyohiko Hatake, Michinori Ogura, Toshiki Uchida, Kiyoshi Ando, Tomohiro Kinoshita, Thomas Höhler, Heribert Stauder, Andreas Kirsch, Michael Koenigsmann, Stephan Kremers, Thomas Illmer, Mathias Witzens-Harig, Paul La Roseé, Jan Dürig, Michael Kneba, Manfred Hensel, Stefan Fuxius, Lothar Bergmann, Kai Hübel, Christian Buske, Reinhard Marks, Gerald Wulf, Christian Lerchenmueller, Rudolf Schmits, Mark Reinwald, Eva Lengfelder, Fiona Scott, Takaaki Chou, Masafumi Taniwaki, Isao Yoshida, Kenichi Ishizawa, Naokuni Uike, Nobuhiko Uoshima, Yuri Kamitsuji, Shinsuke Iida, Ken Ohmine, Kisato Nosaka, Kazuhiko Ide, Takayuki Ishikawa, Pierre Desjardins, Nicholas Finn, Jun Zhu, Wei Li, Li Yu, Hanyun Ren, Yuan Kai Shi, Gang Wu, Xiaonan Hong, Qingyuan Zhang, Jifeng Feng, Rong Zhan, Tongyu Lin, Sirpa Leppa, Regis Costello, Adrian Tempescul, Laurence Sanhes, Olivier Tournilhac, Heinz Kirchen, Holger Hebart, Rudolf Weide, Kathleen Jentsch-Ullrich, Irit Avivi, Arnon Nagler, Ronit Gurion, Ofer Shpilberg, Pietro Leoni, Luca Baldini, Olga Samoylova, Alexandr Myasnikov, Tran-Der Tan, Hung Chang, Kyoya Kumagai, Norifumi Tsukamoto, Kunihiro Tsukasaki, Patrick Beatty, Noriko Usui, Koji Izutsu, Tohru Murayama, Tatsuo Ichinohe, Kohmei Kubo, Fumihiro Ishida, J. Thaddeus Beck, Frank Griesinger, Dzhelil Osmanov, Shaker Dakhil, Aline Clavert, Dai Maruyama, Yasuhito Terui, Kazuhito Yamamoto, Ekkehard Eigendorff, Tsutomu Kobayashi, Satoshi Ichikawa, Ilseung Choi, Katsuya Wada, Yoshitaka Kikukawa, Masao Matsuoka, Takayuki Yoshino, Yosuke Minami, Dürig, Jan (Beitragende*r), The University of Sydney, Service de médecine nucléaire [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Prince of Wales Medical Research Institute, University of New South Wales [Sydney] (UNSW), University of Melbourne, Universiteit Gent = Ghent University [Belgium] (UGENT), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Semmelweis University of Medicine [Budapest], Queens Elizabeth Hospital [Birmingham], Queen Mary University of London (QMUL), IBM Thomas J. Watson Research Center, IBM, Department of Computing and Information Systems, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM)
Subjects: Male, Time Factors, [SDV]Life Sciences [q-bio], Follicular lymphoma, Medizin, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Agents, Immunological, Obinutuzumab, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Prospective Studies, Lymphoma, Follicular, Randomized Controlled Trials as Topic, education.field_of_study, Manchester Cancer Research Centre, Hazard ratio, Middle Aged, Progression-Free Survival, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Female, Immunotherapy, Rituximab, medicine.drug, Bendamustine, medicine.medical_specialty, Population, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Progression-free survival, education, Aged, Neoplasm Staging, Retrospective Studies, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, medicine.disease, chemistry, Clinical Trials, Phase III as Topic, Positron-Emission Tomography, business, Tomography, X-Ray Computed, Progressive disease, 030215 immunology
Abstract: BACKGROUND: Initial results from the ongoing GALLIUM trial have shown that patients with follicular lymphoma have a longer progression-free survival after first-line immunochemotherapy with obinutuzumab than with rituximab. The aim of this secondary analysis was to evaluate the prognostic value of PET-CT responses after first-line immunochemotherapy in the GALLIUM study.METHODS: GALLIUM is an open-label, parallel-group randomised, phase 3 trial, which recruited previously untreated patients with CD20-positive follicular lymphoma (grades 1-3a; disease stage III/IV, or stage II with largest tumour diameter ≥7 cm) who were aged 18 years or older and met the criteria for needing treatment. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous administration of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1, then day 1 of subsequent cycles) or rituximab (375 mg/m2 on day 1 of each cycle), in six 21-day cycles with cyclophosphamide, doxorubicin, vincristine, and prednisone (known as CHOP; oral administration) followed by two 21-day cycles of antibody alone, or eight 21-day cycles cyclophosphamide, vincristine, and prednisone (known as CVP; oral administration), or six 28-day cycles with bendamustine, followed by maintenance antibody every 2 months for up to 2 years. The primary endpoint of the trial, investigator-assessed progression-free survival, has been reported previously. This secondary analysis reports PET and CT-based responses at end-of-induction therapy and explains their relation with progression-free and overall survival outcomes in patients with available scans. As per protocol, during the trial, PET scans (mandatory in the first 170 patients enrolled at sites with available PET facilities, and optional thereafter), acquired at baseline and end of induction (PET population), were assessed prospectively by investigators and an independent review committee (IRC) applying International Harmonisation Project (IHP) 2007 response criteria, and retrospectively by the IRC only applying current Lugano 2014 response criteria. IRC members (but not study investigators) were masked to treatment and clinical outcome when assessing response. The landmark analyses excluded patients who died or progressed (contrast enhanced CT-based assessment of progressive disease, or started next anti-lymphoma treatment) before or at end of induction. GALLIUM is registered at ClinicalTrials.gov, number NCT01332968.FINDINGS: 1202 patients were enrolled in GALLIUM between July 6, 2011, and Feb 4, 2014, of whom 595 were included in the PET population; 533 (IHP 2007; prospective analysis), and 508 (Lugano 2014; retrospective analysis) were analysed for progression-free survival (landmark analysis). At end of induction, 390 of 595 patients (65·5% [95% CI 61·6-69·4]) achieved PET complete response according to IHP 2007 criteria, and 450 (75·6% [95% CI 72·0-79·0]) obtained PET complete metabolic response according to Lugano 2014 criteria. With a median of 43·3 months of observation (IQR 36·2-51·8), 2·5-year progression-free survival from end of induction was 87·8% (95% CI 83·9-90·8) in PET complete responders and 72·0% (63·1-79·0) in non-complete responders according to IRC-assessed IHP 2007 criteria (hazard ratio [HR] 0·4, 95% CI 0·3-0·6, pINTERPRETATION: Our results suggest that PET is a better imaging modality than contrast-enhanced CT for response assessment after first-line immunochemotherapy in patients with follicular lymphoma. PET assessment according to Lugano 2014 response criteria provides a platform for investigation of response-adapted therapeutic approaches. Additional supportive data are welcomed.FUNDING: F Hoffmann-La Roche.
Published: 2018
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108. DNA demethylation marks in chronic lymphocytic leukemia: it is time to let the cat out of the bag

Author: Christelle Le Dantec, Mihnea Zdrenghea, Yves Renaudineau, Cristina Bagacean, Christian Berthou, Adrian Tempescul, LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), 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), Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Nantes Université (Nantes Univ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Michel, Geneviève
Subjects: 0301 basic medicine, DNA Hydroxymethylation, DNA methylation, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], DNMT, Biology, medicine.disease, Virology, Molecular biology, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, DNA demethylation, Editorial, DNA hydroxymethylation, medicine, chronic lymphocytic leukemia, TET, ComputingMilieux_MISCELLANEOUS, Biotechnology
Abstract: International audience
Published: 2018
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109. Valeur pronostique du volume métabolique tumoral total mesuré sur la TEP au 18FDG initiale dans le syndrome de Richter

Author: Habiba Mesbah, Clémence Pontoizeau, Adrian Tempescul, Anne Devillers, X. Palard Novello, Pierre-Yves Salaun, Antoine Girard, F. Le Jeune, and Thierry Lamy
Subjects: Radiological and Ultrasound Technology, Biophysics, Radiology, Nuclear Medicine and imaging
Abstract: Objectifs Le syndrome de Richter est un syndrome rare qui consiste au developpement d’un lymphome agressif (le plus souvent un lymphome B diffus a grandes cellules (DLBCL)) chez les patients atteints d’une leucemie lymphoide chronique (LLC). Ce syndrome represente un veritable challenge clinique compte tenu de son pronostic tres reserve. Le caractere clonal du DLBCL identique a la LLC sous-jacente est le principal facteur de mauvais pronostic. Extrait de la TEP au 18FDG, le volume metabolique tumoral total (TMTV) est un parametre pronostique deja connu du DLBCL de novo, du lymphome de Hodgkin et du lymphome folliculaire. L’objectif est d’etudier ici son interet pronostique dans la transformation en DLBCL de la LLC, plus simple a rechercher que le caractere clonal. Materiels et methodes Vingt-quatre patients d’âge median de 72 ans atteints d’un DLBCL compliquant une LLC et ayant beneficie d’une TEP au 18FDG au moment du syndrome de Richter entre janvier 2012 et avril 2018 ont ete analyses retrospectivement. La survie globale a ete calculee par methode de Kaplan–Meier. Pour identifier les facteurs associes a la survie globale, nous avons compare les courbes de survie selon le log-rank test apres binarisation des parametres quantitatifs par extraction d’un cut-off par courbe ROC des parametres demographiques (âge et sexe), cliniques (performans status et score IPI), biologiques (LDH et plaquettes), la presence ou non d’un traitement de la LLC au prealable et les parametres extraits de la TEP au 18FDG (score d’Ann Arbor, caractere bulky ou non, SUVmax, SUVmean et TMTV). Le TMTV a ete mesure par segmentation des SUV des masses tumorales ganglionnaires et extra-ganglionnaires, avec un seuil a 41 % du SUVmax de chaque lesion. Resultats Le delai de suivi median etait de 16 mois avec une survie globale de 75 %. Seuls les taux de plaquettes, de LDH, le score IPI et le TMTV etaient predictifs de la survie globale (respectivement p = 0,001 ; p = 0,001 ; p = 0,0048 ; p = 0,0043) avec respectivement un cut-off de 134000/mm3, 827 UI/L, score 2 et 50 cm3. En analyse multivariee, aucun parametre n’etait significativement associe a la survie globale. Conclusion Un TMTV > 50 cm3 mesure par TEP au 18FDG au moment de la transformation en DLBCL de la LLC serait associe a une survie globale plus faible. Ces resultats sont a confirmer avec un plus grand nombre de patients.
Published: 2019
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110. Prognostic Value of Baseline Total Metabolic Tumor Volume Measured on FDG PET in Patients With Richter Syndrome

Author: Pontoizeau, Clémence, primary, Girard, Antoine, additional, Mesbah, Habiba, additional, Haumont, Laure-Anne, additional, Devillers, Anne, additional, Tempescul, Adrian, additional, Salaün, Pierre-Yves, additional, Lamy, Thierry, additional, Le Jeune, Florence, additional, and Palard-Novello, Xavier, additional
Published: 2019
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111. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Author: Facon, Thierry, primary, Dimopoulos, Meletios A., additional, Meuleman, Nathalie, additional, Belch, Andrew, additional, Mohty, Mohamad, additional, Chen, Wen-Ming, additional, Kim, Kihyun, additional, Zamagni, Elena, additional, Rodriguez-Otero, Paula, additional, Renwick, William, additional, Rose, Christian, additional, Tempescul, Adrian, additional, Boyle, Eileen, additional, Manier, Salomon, additional, Attal, Michel, additional, Moreau, Philippe, additional, Macro, Margaret, additional, Leleu, Xavier, additional, Lorraine Chretien, Marie, additional, Ludwig, Heinz, additional, Guo, Shien, additional, Sturniolo, Michael, additional, Tinel, Antoine, additional, Silvia Monzini, Mara, additional, Costa, Bruno, additional, Houck, Vanessa, additional, Hulin, Cyrille, additional, and Yves Mary, Jean, additional
Published: 2019
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112. Complement System: a Neglected Pathway in Immunotherapy

Author: Bordron, Anne, primary, Bagacean, Cristina, additional, Tempescul, Adrian, additional, Berthou, Christian, additional, Bettacchioli, Eléonore, additional, Hillion, Sophie, additional, and Renaudineau, Yves, additional
Published: 2019
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113. Apoptotic resistance in chronic lymphocytic leukemia and therapeutic perspectives

Author: Bagacean, Cristina, primary, Tomuleasa, Ciprian, additional, Tempescul, Adrian, additional, Grewal, Ravnit, additional, Brooks, Wesley H., additional, Berthou, Christian, additional, and Renaudineau, Yves, additional
Published: 2019
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114. Valeur pronostique du volume métabolique tumoral total mesuré sur la TEP au 18FDG initiale dans le syndrome de Richter

Author: Pontoizeau, C., primary, Girard, A., additional, Mesbah, H., additional, Tempescul, A., additional, Devillers, A., additional, Salaün, P.Y., additional, Lamy, T., additional, Le Jeune, F., additional, and Palard Novello, X., additional
Published: 2019
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115. Autologous hematopoietic stem cell transplantation in elderly patients (≥70years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study

Author: E, Hermet, A, Cabrespine, R, Guièze, A, Garnier, A, Tempescul, P, Lenain, R, Bouabdallah, J P, Vilque, J, Frayfer, D, Bordessoule, D, Sibon, M, Janvier, D, Caillot, P, Biron, L, Legros, B, Choufi, B, Drenou, N C, Gorin, K, Bilger, J, Tamburini, C, Soussain, S, Brechignac, J O, Bay, and R, Guieze
Subjects: Male, Melphalan, Oncology, medicine.medical_specialty, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Follicular lymphoma, Hematopoietic stem cell transplantation, Disease-Free Survival, Autologous stem-cell transplantation, immune system diseases, hemic and lymphatic diseases, Internal medicine, Prevalence, medicine, Humans, Societies, Medical, Aged, Bone Marrow Transplantation, Retrospective Studies, Aged, 80 and over, business.industry, Incidence, Lymphoma, Non-Hodgkin, Hematopoietic Stem Cell Transplantation, medicine.disease, Surgery, Non-Hodgkin's lymphoma, Lymphoma, Survival Rate, Transplantation, Female, Mantle cell lymphoma, France, Geriatrics and Gerontology, business, Follow-Up Studies, medicine.drug
Abstract: Introduction Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70years of age with non-Hodgkin's lymphoma (NHL). Materials and Methods In the setting of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70years of age who received AHSCT. Results The median age at AHSCT was 72.3years [70–80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×10 9 /L neutrophils and 20×10 9 /L platelets were of 12 [9–76] days and 12 [0–143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. Conclusion In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate.
Published: 2015
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116. Ofatumumab in Refractory Chronic Lymphocytic Leukemia: Experience Through the French Early Access Program

Author: S. de Guibert, S François, Adrien Tempescul, Stéphane Leprêtre, V. Levy, Véronique Morel, Sylvain Choquet, Marie-Sarah Dilhuydy, Pauline Brice, Luc Mathieu Fornecker, Loic Ysebaert, Jehan Dupuis, Interdisciplinary Institute for Neuroscience, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, 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, GlaxoSmithKline, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], 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), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), Hôpital Avicenne, Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Pharmacologie Clinique-CHU Gabriel-Montpied
Subjects: Male, Cancer Research, medicine.medical_specialty, Chronic lymphocytic leukemia, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Ofatumumab, chemistry.chemical_compound, Internal medicine, medicine, Humans, CD20, Adverse effect, Aged, Retrospective Studies, biology, business.industry, Temporary use authorization, Antibodies, Monoclonal, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Surgery, Clinical trial, Treatment Outcome, Oncology, chemistry, Tolerability, Drug Resistance, Neoplasm, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Alemtuzumab, Female, France, Relapsed/refractory, Refractory Chronic Lymphocytic Leukemia, business, CLL, medicine.drug
Abstract: International audience; Background - The Autorisation Temporaire d'Utilisation (ATU) is an early access program available in France for drugs aimed at treating severe diseases not yet covered by a marketing authorization, for patients without any other therapeutic option and who cannot be included in a clinical trial. Patients and methods - This report presents the use of single-agent ofatumumab in 30 patients with advanced chronic lymphocytic leukemia (CLL) in the French ATU program. Results - These very-high-risk patients had received multiple previous treatments (median = 6), and most had disease that was fludarabine-refractory or alemtuzumab-refractory (or both) or was unsuitable for alemtuzumab treatment. In the intent-to-treat analysis, the overall response rate was 47% (4 of 30, complete response; 10 of 30, partial response). Of 13 patients with 17p deletion, 6 displayed response to ofatumumab, including 2 complete responses. Treatment was well tolerated, with 17 grade 3 or 4 adverse events; 4 cases of grade 3 or 4 infusion reactions were reported, with favorable immediate outcome. Among nonhematologic complications, infections were the most frequent. Conclusion - The results confirm the efficacy and acceptable tolerability profile of ofatumumab as a single agent in severely ill patients with CLL. Attention should be paid to possible early infusion reactions to ofatumumab, as well as to the risk of infection.
Published: 2015
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117. Tori et exostoses multiples : présentation d’un cas et revue de la littérature

Author: Caroline Darbin, Cédric Lansonneur, Adrian Tempescul, Pierre Yves Vaillant, Sylvie Boisramé, and Emilie Hascoet
Subjects: Philosophy, Periodontics, Dentistry (miscellaneous), Oral Surgery, Humanities
Abstract: Introduction : Les exostoses et les tori sont des excroissances osseuses benignes ayant differentes localisations. Les facteurs intervenant dans leur apparition sont encore discutes. Ces excroissances sont asymptomatiques, mais elles peuvent parfois occasionner differentes genes. De ce fait, leur exerese n’est que rarement necessaire. Observation : Il s’agit d’une femme de 58 ans presentant des exostoses et des tori maxillaires et mandibulaires volumineux, associes a un bruxisme aggrave ayant entraine des attritions occlusales, une baisse de la dimension verticale d’occlusion et des troubles de l’articulation temporo-manbibulaire. Compte tenu du volume des exostoses mandibulaires vestibulaires, une exerese a ete realisee, associee a la confection d’une plaque de liberation occlusale. Commentaires et conclusion : Ce cas interroge sur la part imputable aux surcharges occlusales dans l’apparition d’exostoses. Une revue de la litterature a ete realisee afin de valider cette possible etiologie, de comprendre comment ameliorer la prise en charge et eviter leur reapparition.
Published: 2015
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118. Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia improves prognosis prediction for patients with isolated 13q deletion

Author: Adrian Tempescul, Anne Bordron, Christelle Le Dantec, Victor Cristea, Yves Renaudineau, Christian Berthou, Hussam Saad, Cristina Bagacean, Nathalie Douet-Guilbert, Mihnea Zdrenghea, LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), 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), Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de cytogénétique [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Laboratoire d'Immunologie et Immunothérapie, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: Epigenomics, Male, 0301 basic medicine, Lymphocytosis, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], lcsh:Medicine, DNMT, DNA Methyltransferase 3A, Mixed Function Oxygenases, DNA (Cytosine-5-)-Methyltransferases, In Situ Hybridization, Fluorescence, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, DNA methylation, Middle Aged, Prognosis, 3. Good health, DNA-Binding Proteins, Cytogenetic Analysis, 5-Methylcytosine, Disease Progression, Female, Chromosome Deletion, medicine.symptom, medicine.medical_specialty, lcsh:QH426-470, Short Report, Biology, Dioxygenases, Cytogenetics, 03 medical and health sciences, Proto-Oncogene Proteins, Complex Karyotype, Genetics, medicine, Humans, Epigenetics, Molecular Biology, Aged, Retrospective Studies, Chromosomes, Human, Pair 13, lcsh:R, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, lcsh:Genetics, 030104 developmental biology, DNA demethylation, Immunology, Cancer research, Active DNA demethylation, Trisomy, TET, Developmental Biology
Abstract: Background Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]). The two 5-cytosine derivatives, 5-methylcytosine (5-mCyt) and 5-hydroxymethylcytosine (5-hmCyt), were tested by ELISA (n = 60), while real-time quantitative PCR was used for determining transcriptional expression levels of DNMT and TET (n = 24). Results By using global DNA methylation/demethylation levels, in the low-risk disease group, two subgroups with significantly different clinical outcomes have been identified (median treatment-free survival [TFS] 45 versus > 120 months for 5-mCyt, p = 0.0008, and 63 versus > 120 months for 5-hmCyt, p = 0.04). A defective 5-mCyt status was further associated with a higher percentage of 13q deleted nuclei (> 80%), thus suggesting an acquired process. When considering the cytogenetic intermediate/high-risk disease groups, an association of 5-mCyt status with lymphocytosis (p = 0.0008) and the lymphocyte doubling time (p = 0.04) but not with TFS was observed, as well as a reduction of DNMT3A, TET1, and TET2 transcripts. Conclusions Combining cytogenetic studies with 5-mCyt assessment adds accuracy to CLL patients’ prognoses and particularly for those with 13q deletion as a sole cytogenetic abnormality.
Published: 2017
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119. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study

Author: Lugtenburg, Pieternella, Avivi, Irit, Berenschot, Henriette, Ilhan, Osman, Marolleau, Jean Pierre, Nagler, Arnon, Rueda, Antonio, Tani, Monica, Turgut, Mehmet, Osborne, Stuart, Smith, Rodney, Pfreundschuh, Michael, Tempescul, Adrian, Tel Aviv Sourasky Medical Center [Te Aviv], CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Saarland University Medical School, CIC Brest, and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche
Subjects: [SDV]Life Sciences [q-bio], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2017

120. Alterations in DNA methylation/demethylation intermediates predict clinical outcome in chronic lymphocytic leukemia

Author: Nathalie Douet-Guilbert, Christelle Le Dantec, Adrian Tempescul, Anne Bordron, Hussam Saad, Cristina Bagacean, Pierre-François Cartron, Valerie Olivier, Christian Berthou, Mihnea Zdrenghea, Victor Cristea, Yves Renaudineau, Audrey Mohr, LabEX IGO Immunothérapie Grand Ouest, 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de cytogénétique [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], and Laboratoire d'Immunologie et Immunothérapie
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Methyltransferase, Chronic lymphocytic leukemia, SAT1, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Epigenetics, Progression-free survival, ComputingMilieux_MISCELLANEOUS, Hematology, business.industry, hydroxymethylation, medicine.disease, 3. Good health, 030104 developmental biology, DNA demethylation, 030220 oncology & carcinogenesis, Immunology, DNA methylation, chronic lymphocytic leukemia, [SDV.IMM]Life Sciences [q-bio]/Immunology, methylation, IGHV@, business, TET, Research Paper
Abstract: // Cristina Bagacean 1, 2, 3 , Adrian Tempescul 1, 4 , Christelle Le Dantec 1 , Anne Bordron 1 , Audrey Mohr 1 , Hussam Saad 4 , Valerie Olivier 2 , Mihnea Zdrenghea 3, 5 , Victor Cristea 3 , Pierre-Francois Cartron 6 , Nathalie Douet-Guilbert 7 , Christian Berthou 1, 4 and Yves Renaudineau 1, 2 1 U1227 B Lymphocytes and Autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, Networks IC-CGO and REpiCGO from Canceropole Grand Ouest, Brest, France 2 Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, France 3 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania 4 Department of Hematology, Brest University Medical School Hospital, Brest, France 5 Department of Hematology, ‘Ion Chiricuta’ Oncology Institute, Cluj-Napoca, Romania 6 Inserm, U892, Epigenetics Network from Canceropole Grand Ouest, Nantes, France 7 Laboratory of Cytogenetics, Brest University Medical School Hospital, Brest, France Correspondence to: Yves Renaudineau, email: yves.renaudineau@univ-brest.fr Keywords: chronic lymphocytic leukemia, methylation, hydroxymethylation, TET, SAT1 Received: June 08, 2017 Accepted: July 26, 2017 Published: August 09, 2017 ABSTRACT Cytosine derivative dysregulations represent important epigenetic modifications whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5-hydroxymethyluracil were tested in purified B cells from CLL patients ( n = 55) and controls ( n = 17). The DNA methylation ‘writers’ (DNA methyltransferases [ DNMT1/3A/3B ]), ‘readers’ (methyl-CpG-binding domain [ MBD2/4 ]), ‘editors’ (ten-eleven translocation [ TET1/2/3 ]) and ‘modulators’ ( SAT1 ) were also evaluated. Accordingly, patients were stratified into three subgroups. First, a subgroup with a global deficit in cytosine derivatives characterized by hyperlymphocytosis, reduced median progression free survival (PFS = 52 months) and shorter treatment free survival (TFS = 112 months) was identified. In this subgroup, major epigenetic modifications were highlighted including a reduction of 5-mCyt, 5-hmCyt, 5-CaCyt associated with DNMT3A , MBD2/4 and TET1/2 downregulation. Second, the cytosine derivative analysis revealed a subgroup with a partial deficit (PFS = 84, TFS = 120 months), mainly affecting DNA demethylation (5-hmCyt reduction, SAT1 induction). Third, a subgroup epigenetically similar to controls was identified (PFS and TFS > 120 months). The prognostic impact of stratifying CLL patients within three epigenetic subgroups was confirmed in a validation cohort. In conclusion, our results suggest that dysregulations of cytosine derivative regulators represent major events acquired during CLL progression and are independent from IGHV mutational status.
Published: 2017
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121. Calcium, une nouvelle piste thérapeutique dans la leucémie lymphoïde chronique

Author: Renaudineau, Yves, Mignen, Olivier, Debant, Marjolaine, Hemon, Patrice, Buscaglia, Paul, Le Goux, Nelig, Berthou, Christian, Tempescul, Adrian, Bagacean, Cristina, Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), 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), LabEX IGO Immunothérapie Grand Ouest, Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

122. La methylation de l'ADN ainsi que les intermédiaires de la déméthylation renseignent sur l'évolution Clinique dans la leucémie lymphoïde chronique

Author: Bagacean, Cristina, Le Dantec, Christelle, Tempescul, Adrian, Berthou, Christian, Bordron, Anne, Charras, Amandine, Renaudineau, Yves, LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Immunologie et Immunothérapie [Brest], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

123. Isolated intra-ocular relapses of primary central nervous system lymphoma

Author: Younan, Nadia, Soussain, Carole, Choquet, Sylvain, Touitou, Valérie, Schmitt, Anna, Chinot, O., Taillandier, Luc, Amiel, Alexandra, Laribi, Kamel, Lamy, Thierry, Ghesquieres, Hervé, Marolleau, Jean-Pierre, Moles-Moreau, Marie-Pierre, Tempescul, Adian, Agape, Philippe, Cassoux, Nathalie, Jardin, Fabrice, Gressin, Rémy, Gyan, Emmanuel, Brion, A., Ahle, Guido, El Yamani, Abderrazak, Bourniquel, Marie, Hoang-Xuan, Khê, Houillier, Caroline, Institut Curie [Paris], CRLCC René Huguenin, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Rabin Medical Center, Centre Hospitalier Le Mans (CH Le Mans), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier de Laval (CH Laval), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 [2016-2019] (UGA [2016-2019]), CHU de Grenoble-Alpes, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de neurologie 2 [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and DESSAIVRE, Louise
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: published in European Journal of Neurology 24(Suppl 1):52, 2017; International audience; Background and aims: Relapses in primary central nervous system lymphoma (PCNSL) are usually cerebral and severe. Isolated intraocular relapses (IIOR) are much rarer and have not been specifically studied so far.Methods: We retrospectively selected patients treated within the French national expert network on PCNSL (LOC network). The inclusion criteria were: histologically proven PCNSL with at least a cerebral localization, immunocompetent status, 1st line treatment based on high-dose methotrexate and isolated IIOR subsequently.Results: 47 patients met the inclusion criteria (median age: 64.5 years (32.8-79.7), median Karnofsky Performance Status (KPS): 70 (40-100)). Initially, 13 patients had an ocular involvement, 16 had no ocular involvement and 18 had unknown status. The IIOR was the first relapse in 80% of cases. Median time from PCNSL diagnosis to IIOR was 14 months (3-51). Median KPS at IIOR was 80 (70-90), the affection was symptomatic in 95%. Decreased visual acuity was the prominent symptom. 76% of the patients received systemic chemotherapy (CT): ifosfamide-based CT (25%), methotrexate-based CT (25%), temozolomide (19%), in association with rituximab in 47%. 32% received a local treatment (intraocular CT or ocular radiotherapy) alone or in association with systemic CT. 31% subsequently received high-dose CT with autologous stem cells rescue). 60% of patients relapsed subsequently (35% in the brain, 62% in the eye) with a median PFS of 10,8 months. 5-year survival rate from relapse was 53.6% (0.28-1).Conclusion: IIOR of PCNSL seem to have a better prognosis than brain relapses. That might be explained by a better KPS allowing intensification chemotherapy for up to the third of patients.
Published: 2017

124. Clinical characteristics of aquagenic pruritus in patients with myeloproliferative neoplasms

Author: Jean-Christophe Ianotto, Laurent Misery, Karine Lacut, Valérie Ugo, Maelenn Gouillou, Jean-Luc Carré, Adrian Tempescul, C. Le Gall‐Ianotto, Emilie Brenaut, Christian Berthou, Emmanuel Nowak, Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie (Dermato - BREST), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Laboratoire d'Hématologie Biologique, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Neurosciences de Brest (LNB), and Calvez, Ghislaine
Subjects: Adult, Pathology, medicine.medical_specialty, Juvenile xanthogranuloma, [SDV]Life Sciences [q-bio], Sweating, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Humans, In patient, Prospective Studies, skin and connective tissue diseases, Myeloproliferative neoplasm, ComputingMilieux_MISCELLANEOUS, Myeloproliferative Disorders, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Hypereosinophilic syndrome, Pruritus, Water, food and beverages, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Aquagenic pruritus, Itching, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Aquagenic pruritus (AP) is a diffuse itching sensation that develops immediately after water contact without any visible skin changes. AP is classically associated with polycythemia vera (PV), a BCR-ABL1-negative myeloproliferative neoplasm (MPN), and can precede the diagnosis of the disease1,2. Alternatively, AP can be drug-induced or associated with various disorders (e.g., myelodysplastic syndrome, hypereosinophilic syndrome, and juvenile xanthogranuloma)3,4. This article is protected by copyright. All rights reserved.
Published: 2017
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125. The arachidonic acid–LTB4–BLT2 pathway enhances human B-CLL aggressiveness

Author: Christian Berthou, Catherine Le Jossic Corcos, Laurent Corcos, Yvonne Dréano, Jean-Pierre Salaün, Jean-Christophe Ianotto, Brigitte Simon, Nathalie Guriec, Adrian Tempescul, Laboratoire de Thérapie Cellulaire, CHU Morvan, Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Département d'hématologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, INSERM, U613, Université de Brest (UBO), Faculté de Médecine, Université européenne de Bretagne - European University of Brittany (UEB), Sanders, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: BLT2, medicine.medical_specialty, Proliferation index, Leukotriene B4, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, PPAR, Flow cytometry, chemistry.chemical_compound, Internal medicine, medicine, Autocrine signalling, Molecular Biology, Disease progression, medicine.diagnostic_test, Leukotriene A4, B-CLL, medicine.disease, Endocrinology, chemistry, LTB4, Cancer research, Molecular Medicine, Arachidonic acid, Intracellular
Abstract: International audience; Deregulation of the oxidative cascade of poly-unsaturated fatty acids (PUFAs) has been associated with several cancers, including chronic lymphocytic leukemia (B-CLL). Leukotriene B4 (LTB4), a metabolite of arachidonic acid (AA), is produced by B-CLL and contributes to their survival. The aim of the present study was to analyze the activity of the oxidative cascade of PUFAs in B-CLL. Purified B cells from patients and normal B CD5 positive cells were subjected to flow cytometry, Western-blot and RT-qPCR analyses. LTB4 plasma and intracellular concentrations were determined by ELISA. Our results showed that aggressive B-CLL tumor cells, i.e. cells with an annual proliferation index above 2, over-expressed calcium-dependent and calcium-independent phospholipases A2 (cPLA2-alpha and iPLA2-beta, respectively), 5-lipoxygenase (5LOX) and leukotriene A4 hydroxylase (LTA4H). Intracellular LTB4 levels were lower in the most aggressive cells than in cells with a smaller proliferation index, despite equivalent plasma levels, and lower expression of cytochrome P450 4F3A (CYP4F3A), one major enzyme involved in LTB4 inactivation. Since BLT2, a LTB4 membrane receptor was also more often expressed on aggressive tumor cells, and since a BLT2 inhibitor significantly impaired B-CLL viability in vitro, we propose that LTB4 was efficiently trapped onto BLT2 present on aggressive tumors, thereby eliciting an autocrine response. Taken together our results demonstrate a major deregulation of the pathway leading to LTB4 synthesis and degradation in B-CLL cells, and provide a framework for understanding how these modifications promote cell survival and proliferation, especially in the most aggressive BCLL.
Published: 2014
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126. The regulatory capacity of B cells directs the aggressiveness of CLL

Author: Mohr, Audrey, primary, Cumin, Marie, additional, Bagacean, Cristina, additional, Pochard, Pierre, additional, Le Dantec, Christelle, additional, Hillion, Sophie, additional, Renaudineau, Yves, additional, Berthou, Christian, additional, Tempescul, Adrian, additional, Saad, Hussam, additional, Pers, Jacques-Olivier, additional, Bordron, Anne, additional, and Jamin, Christophe, additional
Published: 2018
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127. Superiority of Allogenic Stem Cell Transplantation after Anti-PD1 Therapy over Anti-PD1 Monotherapy Alone in Relapse/Refractory Hodgkin Lymphoma: Real World Evidence from the French Early Access Program

Author: Manson, Guillaume, primary, Mear, Jean-Baptiste, additional, Herbaux, Charles, additional, Schiano de Collela, Jean Marc, additional, Casasnovas, Rene-Olivier, additional, Stamatoullas, Aspasia, additional, Deau-Fisher, Bénédicte, additional, Schmitt, Anna, additional, Garnier, Georges, additional, Molina, Lysiane, additional, Bouabdallah, Krimo, additional, Moles, Marie-Pierre, additional, Ghesquieres, Herv, additional, Tempescul, Adrian, additional, Dulery, Remy, additional, Nicolas-Virelizier, Emmanuelle, additional, Delmer, Alain Jacques, additional, Borel, Cecile, additional, Chauchet, Adrien, additional, Dercle, Laurent, additional, Brice, Pauline, additional, and Houot, Roch, additional
Published: 2018
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128. Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial

Author: Trotman, Judith, primary, Barrington, Sally F, additional, Belada, David, additional, Meignan, Michel, additional, MacEwan, Robert, additional, Owen, Carolyn, additional, Ptáčník, Václav, additional, Rosta, András, additional, Fingerle-Rowson, Günter R, additional, Zhu, Jiawen, additional, Nielsen, Tina, additional, Sahin, Deniz, additional, Hiddemann, Wolfgang, additional, Marcus, Robert E, additional, Davies, Andrew, additional, Hertzberg, Mark, additional, Grigg, Andrew, additional, Cannell, Paul, additional, Quach, Hang, additional, Opat, Stephen, additional, Tam, Constantine, additional, Marlton, Paula, additional, Janssens, Ann, additional, Offner, Fritz, additional, Van eygen, Koen, additional, Sangha, Randeep, additional, Mckay, Pam, additional, Wilson, Jonathan, additional, Van Der Jagt, Richard, additional, Roitman, Daryl, additional, Trneny, Marek, additional, Mayer, Jiri, additional, Le Du, Katell, additional, Solal-Celigny, Philippe, additional, Cartron, Guillaume, additional, Foussard, Charles, additional, Frickhofen, Norbert, additional, Schmidt, Peter, additional, Graeven, Ullrich, additional, Gaska, Tobias, additional, Schlag, Rudolf, additional, Sökler, Martin, additional, Prange-Krex, Gabriele, additional, Florschütz, Axel, additional, Lindemann, Hans-Walter, additional, Schimmelpfennig, Christoph, additional, Tonndorf, Solveig, additional, Hänel, Mathias, additional, Hess, Georg, additional, Schalk, Enrico, additional, Hütten, Heiko, additional, Doelken, Gottfried, additional, Pfreundschuh, Michael, additional, Keller, Ulrich, additional, Herold, Michael, additional, Forstpointner, Roswitha, additional, Vehling-Kaiser, Ursula, additional, Hoffmann, Martin, additional, Borbenyi, Zita, additional, Udvardy, Miklos, additional, Demeter, Judit, additional, Rambaldi, Alessandro, additional, Morra, Enrica, additional, Massimo, Federico, additional, Majolino, Ignazio, additional, Balzarotti, Monica, additional, Semenzato, Gianpietro, additional, Canales Albendea, Miguel Angel, additional, Peñalver Parraga, Francisco Javier, additional, Soler Campos, Alfonso, additional, Sancho Cia, Juan Manuel, additional, Marquez Navarro, Jose Antonio, additional, Grande Garcia, Carlos, additional, Nilsson-Ehle, Herman, additional, Mccarthy, Helen, additional, Pocock, Chris, additional, Sadullah, Shalal, additional, Malladi, Ram, additional, Radford, John, additional, Kanfer, Ed, additional, Kruger, Anton, additional, Culligan, Dominic, additional, Dyer, Martin, additional, Pettengell, Ruth, additional, Seymour, John, additional, Gribben, John, additional, Al-Ismail, Saad, additional, Al-Refaie, Faris, additional, Blesing, Norbert, additional, Macnamara, Christopher, additional, O'callaghan, Ann, additional, Haynes, Andrew, additional, Follows, George, additional, Johnson, Roderick, additional, Cunningham, David, additional, Bowles, Kristian, additional, Collins, Graham, additional, Gallop-Evans, Eve, additional, Robinson, Stephen, additional, Subash, Chezhian, additional, Bailey, James, additional, Holden, Viran, additional, Neidhart, Jeffrey, additional, De Oliveira, Moacyr, additional, Tezcan, Haluk, additional, Kim, Kevin, additional, Kambhampati, Suman, additional, Lanier, Keith, additional, Mcclean, John, additional, Tobinai, Kensei, additional, Hatake, Kiyohiko, additional, Ogura, Michinori, additional, Uchida, Toshiki, additional, Ando, Kiyoshi, additional, Kinoshita, Tomohiro, additional, Höhler, Thomas, additional, Stauder, Heribert, additional, Kirsch, Andreas, additional, Koenigsmann, Michael, additional, Kremers, Stephan, additional, Illmer, Thomas, additional, Witzens-Harig, Mathias, additional, La Roseé, Paul, additional, Dürig, Jan, additional, Kneba, Michael, additional, Hensel, Manfred, additional, Fuxius, Stefan, additional, Bergmann, Lothar, additional, Hübel, Kai, additional, Buske, Christian, additional, Marks, Reinhard, additional, Wulf, Gerald, additional, Lerchenmueller, Christian, additional, Schmits, Rudolf, additional, Reinwald, Mark, additional, Lengfelder, Eva, additional, Scott, Fiona, additional, Chou, Takaaki, additional, Taniwaki, Masafumi, additional, Yoshida, Isao, additional, Ishizawa, Kenichi, additional, Uike, Naokuni, additional, Uoshima, Nobuhiko, additional, Kamitsuji, Yuri, additional, Iida, Shinsuke, additional, Ohmine, Ken, additional, Nosaka, Kisato, additional, Ide, Kazuhiko, additional, Ishikawa, Takayuki, additional, Desjardins, Pierre, additional, Finn, Nicholas, additional, Zhu, Jun, additional, Li, Wei, additional, Yu, Li, additional, Ren, Hanyun, additional, Shi, Yuan Kai, additional, Wu, Gang, additional, Hong, Xiaonan, additional, Zhang, Qingyuan, additional, Feng, Jifeng, additional, Zhan, Rong, additional, Lin, Tongyu, additional, Leppa, Sirpa, additional, Costello, Regis, additional, Tempescul, Adrian, additional, Sanhes, Laurence, additional, Tournilhac, Olivier, additional, Kirchen, Heinz, additional, Hebart, Holger, additional, Weide, Rudolf, additional, Jentsch-Ullrich, Kathleen, additional, Avivi, Irit, additional, Nagler, Arnon, additional, Gurion, Ronit, additional, Shpilberg, Ofer, additional, Leoni, Pietro, additional, Baldini, Luca, additional, Samoylova, Olga, additional, Myasnikov, Alexandr, additional, Tan, Tran-Der, additional, Chang, Hung, additional, Kumagai, Kyoya, additional, Tsukamoto, Norifumi, additional, Tsukasaki, Kunihiro, additional, Beatty, Patrick, additional, Usui, Noriko, additional, Izutsu, Koji, additional, Murayama, Tohru, additional, Ichinohe, Tatsuo, additional, Kubo, Kohmei, additional, Ishida, Fumihiro, additional, Beck, J. Thaddeus, additional, Griesinger, Frank, additional, Osmanov, Dzhelil, additional, Dakhil, Shaker, additional, Clavert, Aline, additional, Maruyama, Dai, additional, Terui, Yasuhito, additional, Yamamoto, Kazuhito, additional, Eigendorff, Ekkehard, additional, Kobayashi, Tsutomu, additional, Ichikawa, Satoshi, additional, Choi, Ilseung, additional, Wada, Katsuya, additional, Kikukawa, Yoshitaka, additional, Matsuoka, Masao, additional, Yoshino, Takayuki, additional, and Minami, Yosuke, additional
Published: 2018
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129. DNA demethylation marks in chronic lymphocytic leukemia: it is time to let the cat out of the bag

Author: Bagacean, Cristina, primary, Zdrenghea, Mihnea, additional, Dantec, Christelle Le, additional, Tempescul, Adrian, additional, Berthou, Christian, additional, and Renaudineau, Yves, additional
Published: 2018
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130. ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

Author: Ungur R, Tempescul A, Berthou C, Bagacean C, Radeanu D, Muresan A, and Zdrenghea M
Subjects: lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract: Rodica Ungur,1,2 Adrian Tempescul,3 Christian Berthou,3 Cristina Bagacean,1,2 Doinel Radeanu,1 Adriana Muresan,1 Mihnea Zdrenghea1,21Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, 2Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest Teaching Hospital, Brest, FranceAbstract: Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum) chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.Keywords: cerebral lymphoma, PCNSL, refractory, relapsed, platinum
Published: 2015

131. Exudative pericarditis in the evolution of a diffuse large B-cell lymphoma

Author: Dana Pop, Mihnea Zdrenghea, Jean-Christophe Ianotto, Véronique Marion, Adrian Tempescul, Cristina Bagacean, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), 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)-Université de Brest (UBO), Laboratoire d'hématologie, Hôpital Morvan [Brest], Cardiology Department (CardioDep - CLUJ-NAPOCA), Rehabilitation Hospital, and 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca
Subjects: Male, Pathology, medicine.medical_specialty, lymphomatous pericarditis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Case Report, 030204 cardiovascular system & hematology, Multimodal Imaging, Cardiac Ultrasound, 03 medical and health sciences, Pericarditis, Fatal Outcome, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, cardiac involvement, medicine, Humans, Chemotherapy, medicine.diagnostic_test, business.industry, Exudates and Transudates, General Medicine, Middle Aged, medicine.disease, 3. Good health, Lymphoma, Positron emission tomography, Positron-Emission Tomography, DLBCL, 030220 oncology & carcinogenesis, Heart failure, Lymphoma, Large B-Cell, Diffuse, Lymph, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Diffuse large B-cell lymphoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Cardiac involvement in non-Hodgkin's lymphoma is a rare occurrence with a dismal prognosis, which may evolve with different clinical presentations, the most frequent being heart failure. Diagnosis of cardiac involvement is generally made by cardiac ultrasound. We report a case of lymphomatous pericarditis in the evolution of a non-Hodgkin's lymphoma, diagnosed by PET-CT scan, and occurring concomitantly with complete isotopic remission of enlarged mediastinal lymph nodes following chemotherapy.
Published: 2015
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132. Biosimilars of filgrastim in autologous stem cell transplant: reduction in granulocyte-colony stimulating factor costs, but similar effects on bone marrow recovery

Author: Christian Berthou, Marie-Anne Couturier, Pascal Delépine, Jean-Christophe Ianotto, Françoise Ngo Sack, Adrian Tempescul, Nathalie Mugnier, Gaelle Guillerm, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Hematology service, Hôpital Central de Yaoude, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Université européenne de Bretagne ( UEB ), Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Eléments transposables, évolution, populations, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), 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), Université européenne de Bretagne - European University of Brittany (UEB), and Michel, Geneviève
Subjects: Male, Oncology, Cancer Research, Lymphoma, MESH : Retrospective Studies, MESH : Aged, MESH: Multiple Myeloma, MESH: Recombinant Proteins, MESH : Granulocyte Colony-Stimulating Factor, MESH: Drug Costs, hemic and lymphatic diseases, Granulocyte Colony-Stimulating Factor, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Prospective cohort study, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Biosimilar, Hematology, Middle Aged, MESH : Adult, Recombinant Proteins, MESH: Transplantation, Autologous, 3. Good health, Granulocyte colony-stimulating factor, Treatment Outcome, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Multiple Myeloma, medicine.drug, Adult, medicine.medical_specialty, MESH : Transplantation, Autologous, [SDV.IMM] Life Sciences [q-bio]/Immunology, Filgrastim, MESH: Biosimilar Pharmaceuticals, MESH : Recombinant Proteins, MESH : Male, MESH : Treatment Outcome, Transplantation, Autologous, MESH : Lymphoma, Drug Costs, MESH : Drug Costs, MESH : Hematopoietic Stem Cell Transplantation, Internal medicine, medicine, Humans, MESH : Middle Aged, Biosimilar Pharmaceuticals, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, MESH: Male, Surgery, Transplantation, MESH : Biosimilar Pharmaceuticals, MESH: Granulocyte Colony-Stimulating Factor, Bone marrow, MESH: Lymphoma, MESH : Multiple Myeloma, business, MESH: Female
Abstract: International audience; Granulocyte-colony stimulating factors (G-CSFs) enhance bone marrow (BM) recovery after autologous stem cell transplant (ASCT) in patients with lymphoma and myeloma. Few publications exist that discuss the use of filgrastim biosimilars after ASCT. We conducted a single-center retrospective study in patients with lymphoma and myeloma treated at Brest Hospital to assess the cost reductions related to and the efficiency and safety of filgrastim biosimilars. We identified 65 patients with lymphoma or myeloma treated with filgrastim biosimilars for ASCT and compared 19 parameters of these patients, including BM recovery, side effects, infectious complications and treatment costs, with published historical data on a cohort of 50 patients treated with classic filgrastim. We observed a significant reduction of G-CSF costs in both groups but did not observe a change in total hospitalization costs (representing less than 2% of the costs) between groups. Additionally, we did not observe differences between the two groups in BM recovery, infectious complications, side effects or the other studied parameters. In this retrospective study, the absence of differences between groups after ASCT in lymphoma and myeloma led us to believe that these drugs could be safely and effectively used for such indications without a significant impact on hospitalization costs. A prospective study should be conducted to confirm our results.
Published: 2013
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133. Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies

Author: Ilcus,Cristina, Bagacean,Cristina, Tempescul,Adrian, Popescu,Cristian, Parvu,Andrada, Cenariu,Mihai, Bocsan,Corina, Zdrenghea,Mihnea, Ilcus,Cristina, Bagacean,Cristina, Tempescul,Adrian, Popescu,Cristian, Parvu,Andrada, Cenariu,Mihai, Bocsan,Corina, and Zdrenghea,Mihnea
Abstract: Cristina Ilcus,1 Cristina Bagacean,1,2 Adrian Tempescul,3 Cristian Popescu,1 Andrada Parvu,1,4 Mihai Cenariu,5 Corina Bocsan,6,* Mihnea Zdrenghea1,4,* 1Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHRU Morvan, 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest, France; 4Department of Hematology, Ion Chiricuta Oncology Institute, 5Biotechnology Research Center, University of Agricultural Sciences and Veterinary Medicine, 6Department of Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania *These authors contributed equally to this work Abstract: The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune effector cells, is credited with a protective role for normal tissue during immune responses, by limiting the extent of effector activation. Its presently known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a variety of cells including cancer cells, suggesting a role for these molecules as an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has recently been shown to be effective and was clinically approved in relapsed/refractory tumors such as malignant melanoma and lung cancer, but also classical Hodgkin’s lymphoma. A plethora of trials exploring PD-1 blockade in cancer are ongoing. Here, we review the role of PD-1 signaling in lymphoid malignancies, and the latest results of trials investigating PD-1 or PD-L1 blocking agents in this group of diseases. Early phase studies proved very promising, leading to the clinical approval of a PD-1 blocking agent in Hodgkin’s lymphoma, and Phase III clinical studies are either planned or ongoing in most lymphoid malignancies. Keywords: immune checkpoint blockade, programmed cell death 1, b7 antigens, hematological cancer, lympho
Published: 2017

134. Atypical aleukemic presentation of large granular lymphocytic leukemia: a case report

Author: Cristina Bagacean, Horia Bumbea, Bogdan Fetica, Mariana Patiu, Mihnea Zdrenghea, Adrian Tempescul, LabEX IGO Immunothérapie Grand Ouest, 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca, Department of Hematology, Ion Chiricuta Oncology Insitute, 'Ion Chiricuta' Cancer Institute, University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Large granular lymphocytic leukemia, Case Report, 030204 cardiovascular system & hematology, Neutropenia, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, lymphoproliferative, medicine, neutropenia, Pharmacology (medical), Bortezomib, business.industry, bortezomib, medicine.disease, 3. Good health, Regimen, Felty, Oncology, large granular lymphocytes, 030220 oncology & carcinogenesis, Immunology, Proteasome inhibitor, [SDV.IMM]Life Sciences [q-bio]/Immunology, Methotrexate, business, medicine.drug
Abstract: International audience; Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of transformed natural killer or T-cells attributed to chronic exposure to the proinflammatory cytokine IL-15. Diagnosis of the majority of T-cell LGLL is established by documenting clonal large granular lymphocytes (LGLs) in peripheral blood, by morphology and immunophenotype. The proteasome inhibitor bortezomib is known to target molecular pathways downstream of the IL-15 receptor signaling and has been proposed as a therapy in these patients. We report an uncommon presentation of LGLL with chronic neutropenia lacking typical blood LGLs, which failed to respond to bortezomib but obtained a very good partial remission with a classical methotrexate regimen.
Published: 2016

135. DNA methylation and demethylation in chronic lymphocytic leukemia

Author: Bagacean, Cristina, Le Dantec, Christelle, Charras, Amandine, Berthou, Christian, Tempescul, Adrian, Zdrenghea, Mihnea, Cristea, Victor, Renaudineau, Yves, Lymphocyte B et Auto-immunité (LBAI), 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), LabEX IGO Immunothérapie Grand Ouest, Department of Clinical Hematology, Institute of Cancerology and Hematology, University Hospital Brest, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHU Morvan, 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Laboratoire d'Immunologie et Immunothérapie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

136. Appraisal of IgM Kappa /IgM lambda variations using Hevy Life after rituximab as consolidation therapy in patients with Walldenström's macroglobulinemia

Author: Eveillard, Jean-Richard, Achour, Achouak, N'Go Sack, Françoise, Tempescul, Adrian, Le Calloc'H, Ronan, Dagorne, Anaïg, Bendaoud, Boutahar, Berthou, Christian, Hillion, Sophie, Renaudineau, Yves, 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, Laboratoire d'Immunologie et Immunothérapie, and Michel, Geneviève
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

137. Evaluation of the novel HevyLife IgM Kappa/IgM Lambda assays in Waldenström's macroglobulinemia patients after rituximab consolidation therapy

Author: Eveillard, Jean-Richard, Achour, Achouak, N'Go, Sack, Tempescul, Adrian, Le Calloc'H, Ronan, Dagorne, Anaïg, Bendaoud, Boutahar, Berthou, Christian, Hillion, Sophie, Renaudineau, Yves, 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, Laboratoire d'Immunologie et Immunothérapie, and Michel, Geneviève
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

138. Late relapsing mantle cell lymphoma showing preserved sensitivity to single-agent lenalidomide

Author: Cristina Bagacean, Mihnea Zdrenghea, Jean-Christophe Ianotto, Corina Bocsan, Adrian Tempescul, Pierre-Yves Salaun, 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), LabEX IGO Immunothérapie Grand Ouest, CHRU Brest - Service de médecine nucléaire (CHU - BREST - Med Nucléaire), Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, and 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca
Subjects: Oncology, medicine.medical_specialty, MESH: Remission Induction, health care facilities, manpower, and services, Lymphoma, Mantle-Cell, Disease, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Immunologic Factors, Single agent, Relapse, IMiD, Lenalidomide, Aged, MESH: Treatment Outcome, MESH: Aged, Hematology, Mantle cell lymphoma, MESH: Humans, business.industry, MESH: Immunologic Factors, Remission Induction, MESH: Thalidomide, medicine.disease, Thalidomide, 3. Good health, MESH: Recurrence, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Immunology, Refractory Mantle Cell Lymphoma, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Lymphoma, Mantle-Cell, business, 030215 immunology, medicine.drug
Abstract: International audience; Mantle cell lymphoma is a hematologic malignancy characterized by poor therapeutic outcomes. Immunomodulatory drugs are a focus of attention in this disease, especially for the elderly and frail patients not able to tolerate the typically intensive therapeutic approaches used in fitter patients. We here present the case of refractory mantle cell lymphoma of the elderly that achieved complete remission following the use of single-agent lenalidomide, and a second complete response to the same regimen on relapse 5 years later.
Published: 2016

139. The bendamustine plus rituximab regimen is active against primary nodal marginal zone B-cell lymphoma: Bendamustine-rituximab in nodal MZL

Author: Alix Baugier de Materre, Delphine Bolle, Adrien Tempescul, Anne Besançon, Stéphanie Poulain, Catherine Truong, Kamel Laribi, Jonathan Farhi, Pierre Lemaire, Jean Christophe Ianotto, Andreea Anghel, Habib Ghnaya, Nathalie Denizon, Centre hospitalier du Mans, Centre Hospitalier Le Mans (CH Le Mans), and Pôle Santé Sud
Subjects: Bendamustine, Cancer Research, medicine.medical_specialty, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Nodal marginal zone B cell lymphoma, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Secondary Myelodysplastic Syndrome, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, medicine.disease, 3. Good health, Surgery, Regimen, Oncology, 030220 oncology & carcinogenesis, Rituximab, business, 030215 immunology, medicine.drug, Rare disease
Abstract: International audience; Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m2 of rituximab on day 1 and 90 mg/m2 of bendamustine on days 1 and 2. The overall and complete response rates were 93% and 71%, respectively. Major toxicity (grade 3/4 neutropenia) occurred in 5% of treatment courses. After a median follow-up of 22 months (range: 18-55), the overall survival and the free survival rates were 100% and 93%, respectively. None of the patients showing a complete or partial response developed secondary myelodysplastic syndrome/acute myeloid leukemia. Bendamustine plus rituximab was found to be an active and well-tolerated regimen leading to the rapid control of disease.
Published: 2016
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140. The bendamustine plus rituximab regimen is active against primary nodal marginal zone B-cell lymphoma

Author: Kamel, Laribi, Adrien, Tempescul, Habib, Ghnaya, Nathalie, Denizon, Anne, Besançon, Andreea, Anghel, Jonathan, Farhi, Catherine, Truong, Pierre, Lemaire, Stephanie, Poulain, Delphine, Bolle, Jean Christophe, Ianotto, and Alix, Baugier de Materre
Subjects: Aged, 80 and over, Male, Survival Rate, Antineoplastic Agents, Immunological, Bendamustine Hydrochloride, Humans, Female, Lymphoma, B-Cell, Marginal Zone, Middle Aged, Rituximab, Aged
Abstract: Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m
Published: 2016

141. Primary CNS lymphoma at first relapse/progression: characteristics, management, and outcome of 256 patients from the French LOC network

Author: Olivier Chinot, D. Larrieu, Sophie Langner-Lemercier, Hervé Ghesquières, Fabrice Jardin, Luc Taillandier, Thierry Lamy, Khê Hoang-Xuan, Emmanuel Gyan, Pierre Soubeyran, Remy Gressin, Annie Brion, Cécile Moluçon-Chabrot, Olivier Casasnovas, Franck Morschhauser, Jean-Pierre Marolleau, Carole Soussain, Guido Ahle, Caroline Houillier, Florian Naudet, Alexandra Benouaich-Amiel, Sylvain Choquet, Ghandi Damaj, Philippe Colin, Michel Fabbro, Arnaud Jaccard, Roch Houot, Marie-Pierre Moles-Moreau, Pascal Bourquard, Oumedaly Reman, Adrian Tempescul, CHU Pontchaillou [Rennes], Centre de référence sur les démences rares et maladie de Pick, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Hématologie (FNCLCC), Centre Léon Bérard [Lyon], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Service de Neuro-Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, 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), Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, CHU Amiens-Picardie, Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service d'hématologie clinique, CHU Grenoble, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de radiothérapie [Reims], Institut du cancer Courlancy-Reims, 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 clinique des Maladies du Sang, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], OncoNeuroTek [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Microenvironnement et cancer (MiCa), 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 ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut National du Cancer (INCa), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou, Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), and Service de neurologie 1 [CHU Pitié-Salpétrière]
Subjects: Oncology, Male, Cancer Research, Palliative care, [SDV]Life Sciences [q-bio], Salvage therapy, Central Nervous System Neoplasms, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Prospective cohort study, relapse, Aged, 80 and over, Progression, Lymphoma, Non-Hodgkin, Primary central nervous system lymphoma, Hematopoietic Stem Cell Transplantation, Middle Aged, Prognosis, Chemotherapy regimen, Combined Modality Therapy, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Disease Progression, Female, Adult, medicine.medical_specialty, Transplantation, Autologous, 03 medical and health sciences, primary CNS lymphoma, Internal medicine, medicine, Humans, Progression-free survival, Clinical Investigation, Survival rate, Aged, Neoplasm Staging, Salvage Therapy, business.industry, medicine.disease, Surgery, Transplantation, Drug Resistance, Neoplasm, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract: International audience; Background - Treatment of relapsed/refractory (R/R) primary CNS lymphoma (PCNSL) is poorly defined, because randomized trials and large studies are lacking. The aim of this study was to analyze the characteristics, management, and outcome of R/R PCNSL patients after first-line therapy in a nationwide cohort.Methods - We analyzed R/R PCNSL patients following first-line treatment who had been prospectively registered in the database of the French network for oculocerebral lymphoma (LOC) between 2011 and 2014.Results - Among 563 PCNSL patients treated with first-line therapy, we identified 256 with relapsed (n = 93, 16.5%) or refractory (n = 163, 29.0%) disease. Patients who were asymptomatic at relapse/progression (25.5%), mostly diagnosed on routine follow-up neuroimaging, tended to have a better outcome. Patients who received salvage therapy followed by consolidation (mostly intensive chemotherapy plus autologous hematopoietic stem cell transplantation [ICT + AHSCT]) experienced prolonged survival compared with those who did not receive salvage or consolidation therapy. Independent prognostic factors at first relapse/progression were: KPS ≥ 70 vs KPS < 70), sensitivity to first-line therapy (relapsed vs refractory disease), duration of first remission (progression-free survival [PFS] ≥1 y vs Conclusions - About a third of PCNSL patients are primary refractory to first line treatment. We identified several independent prognostic factors that can guide the management of R/R PCNSL patients.
Published: 2016
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142. FDG PET/CT for Initial Staging of Diffuse Large B-Cell Lymphoma: Is Diffuse Bone Marrow Uptake a Reflection of Disease Involvement?

Author: Adrian Tempescul, Pierre-Yves Salaun, Xavier Palard, Solène Querellou, Christian Berthou, Philippe Robin, Ronan Abgral, Naelle Lombion, Nathalie Keromnes, Pierre-Yves Le Roux, Service de médecine nucléaire [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [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)-Université de Brest (UBO), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Subjects: medicine.diagnostic_test, business.industry, Standardized uptake value, Disease, medicine.disease, Fibrinogen, 3. Good health, 030218 nuclear medicine & medical imaging, Lymphoma, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Positron emission tomography, 030220 oncology & carcinogenesis, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Fdg pet ct, Bone marrow, business, Nuclear medicine, Diffuse large B-cell lymphoma, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Objectives: Bone marrow assessment is a diagnostic challenge in staging diffuse large B-cell lymphoma (DLBCL). Diffuse bone marrow uptake (BMU) can be observed on FDG PET/CT performed for initial staging of DLBCL, but remains difficult to analyze. The aim of this study was to evaluate the meaning of this diffuse BMU, and especially to assess its correlation with bone marrow involvement (BMI). Methods: Patients who underwent FDG PET/CT for initial staging of DLBCL were analyzed. Diffuse BMU was assessed using a visual qualitative analysis according to liver uptake (grade 1=below liver uptake, 2=equal to liver uptake, 3=above liver uptake), and a semi-quantitative analysis, by measurement of maximum standardized uptake value (SUV) in the sacral promontory. We compared the BMU with BMI, parameters of disease extension and inflammatory markers. Results: 86 patients (median age 59, range: 19-91, 54 men, 32 women) were included. BMU grade was 1, 2 and 3 in 45, 28 and 13 cases respectively. Bone marrow was considered involved in 13 patients. No statistical correlation was found between diffuse BMU and BMI, using qualitative (p=0.594) or semi-quantitative method (p=0.116). Diffuse BMU visual grading was correlated with inflammatory markers: biological systemic symptoms (p=0.003), CRP (p=0.002) and fibrinogen (p=0.020). Conclusions: Our study suggests that a diffuse BMU seen on FDG PET/CT at initial staging of DLBCL is not representative of bone marrow involvement, but can be due to inflammatory changes.
Published: 2016
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143. Isolated Cardiac Richter Syndrome: a Case Report

Author: Mihnea Zdrenghea, Horia Marin, Dana Pop, Pierre-Yves Salaun, Adrian Tempescul, Cristina Bagacean, Yves Renaudineau, Michel, Geneviève, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca, LabEX IGO Immunothérapie Grand Ouest, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de médecine nucléaire [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [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)-Université de Brest (UBO), Departement of Radiology Neuroscience Institute (Henry Ford Health System), Henry Ford Health System, Cardiology Department (CardioDep - CLUJ-NAPOCA), Rehabilitation Hospital, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Morvan [Brest]-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), and CHRU Brest - Service de médecine nucléaire (CHU - BREST - Med Nucléaire)
Subjects: Richter syndrome, Pathology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Heart neoplasms, 0302 clinical medicine, Neoplasm Recurrence, Autologous stem-cell transplantation, Internal medicine, medicine, B cell, ComputingMilieux_MISCELLANEOUS, Hematology, business.industry, General Medicine, medicine.disease, Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience
Published: 2016

144. FIRST LINE TREATMENT BY THE RIBVD REGIMEN ELICITS HIGH CLINICAL AND MOLECULAR RESPONSE RATES AND PROLONGED SURVIVAL IN ELDERLY MCL PATIENTS; FINAL RESULTS OF a LYSA GROUP TRIAL

Author: Jehan Dupuis, Selim Corm, Remy Gressin, Roch Houot, Christiane Mounier, Sylvain Carras, Caroline Dartigeas, M. Macro, Ghandi Damaj, Nicolas Daguindau, Mary Callanan, Jean-Michel Pignon, Anne-Sophie Moreau, S. Le Gouill, Adrien Tempescul, P. Feugier, Fabrice Jardin, Guillaume Cartron, Luc Mathieu Fornecker, I. Ysebaert, A. Bannos, Lionel Karlin, J. Fleury, Anna Schmitt, and Cecile Chabrot
Subjects: Cancer Research, Pediatrics, medicine.medical_specialty, Group trial, business.industry, Hematology, General Medicine, First line treatment, 03 medical and health sciences, Regimen, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Molecular Response, Internal medicine, medicine, business, 030215 immunology
Published: 2017
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145. Le syndrome thoracique aigu de l’adulte drépanocytaire

Author: Francis Couturaud, A. Tempescul, Christophe Leroyer, G. Quéré, N. Paleiron, and L. de Saint-Martin
Subjects: Pulmonary and Respiratory Medicine, Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, medicine, 030212 general & internal medicine, 030204 cardiovascular system & hematology, business, 3. Good health
Abstract: Resume La drepanocytose est une pathologie repandue mais parfois mal apprehendee par les pneumologues qui y sont peu confrontes. Elle merite d’etre connue, compte tenu de sa principale complication respiratoire : le syndrome thoracique aigu (STA). Etat des connaissances La drepanocytose est une maladie autosomique recessive provoquant dans certaines conditions, une falciformation des hematies. Elle touche principalement les individus originaires des pays d’Afrique centrale, de l’ouest et des Antilles. Le STA associe une douleur thoracique ou de la fievre a des infiltrats radiologiques d’apparition recente, chez un individu porteur d’un syndrome drepanocytaire majeur. Ses principales etiologies sont l’infection, l’embolie graisseuse, et l’hypoventilation alveolaire. Il est cependant souvent difficile d’en determiner l’etiologie car il realise un cercle vicieux auto-entretenu. Les bases de la prise en charge, largement sous-evaluees, reposent sur le traitement etiologique, et les mesures visant a eviter l’aggravation liee principalement aux complications, en particulier microcirculatoires, de la maladie. Conclusions Le STA est une complication respiratoire grave de la drepanocytose a laquelle le pneumologue peut etre amene a etre confronte. Une prise en charge adaptee et rapide est necessaire. Les mesures therapeutiques sont simples mais sous-evaluees.
Published: 2011
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146. Peripheral blood stem cell collection in elderly patients

Author: Ljubomir Petrov, Francoise Quivoron, Adrian Tempescul, Jean-Christophe Ianotto, Christian Berthou, Elisabeth Hardy, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), EFS Bretagne, Université européenne de Bretagne - European University of Brittany (UEB), and Michel, Geneviève
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphoma, CD34, Antigens, CD34, Cell Count, MESH: Multiple Myeloma, MESH: Peripheral Blood Stem Cell Transplantation, Peripheral Blood Stem Cells, MESH: Hematopoietic Stem Cell Mobilization, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Aged, Retrospective Studies, MESH: Age Factors, MESH: Aged, Peripheral Blood Stem Cell Transplantation, MESH: Humans, Hematology, MESH: Cell Count, business.industry, Age Factors, MESH: Retrospective Studies, Retrospective cohort study, MESH: Antigens, CD34, General Medicine, medicine.disease, Hematopoietic Stem Cell Mobilization, 3. Good health, Surgery, MESH: Blood Component Removal, Apheresis, Peripheral blood stem cell collection, 030220 oncology & carcinogenesis, Blood Component Removal, Feasibility Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, Multiple Myeloma, MESH: Feasibility Studies, MESH: Lymphoma, business, 030215 immunology
Abstract: International audience; Intensive treatments like autologous blood stem cell transplantations are standard consolidation treatments for lymphoma and myeloma in young people. The upper age limit for these procedures is constantly increasing. Instead of studying the impact of aging on harvesting peripheral blood stem cells (PBSC), we performed a retrospective study to explore the feasibility of collecting stem cells from patients older than 65 years and compared the efficacy to harvest in younger patients. During a period of 7 years, we identified 108 patients with myeloma or lymphoma who were older than 65 years who underwent PBSC collection. Only eight patients failed to produce a successful harvest. The majority of patients only needed one apheresis (71%). There was a median number of 5.3 x 10(6) CD34+ cells/kg. Our study demonstrated that older patients can also undergo PBSC harvests similar to younger patients.
Published: 2009
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147. Non-adherence to treatment with cytoreductive and/or antithrombotic drugs is frequent and associated with an increased risk of complications in patients with polycythemia vera or essential thrombocythemia (OUEST study)

Author: Le Calloch, Ronan, primary, Lacut, Karine, additional, Le Gall-Ianotto, Christelle, additional, Nowak, Emmanuel, additional, Abiven, Morgane, additional, Tempescul, Adrian, additional, Dalbies, Florence, additional, Eveillard, Jean-Richard, additional, Ugo, Valérie, additional, Giraudier, Stéphane, additional, Guillerm, Gaëlle, additional, Lippert, Eric, additional, Berthou, Christian, additional, and Ianotto, Jean-Christophe, additional
Published: 2017
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148. Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia improves prognosis prediction for patients with isolated 13q deletion

Author: Bagacean, Cristina, primary, Le Dantec, Christelle, additional, Berthou, Christian, additional, Tempescul, Adrian, additional, Saad, Hussam, additional, Bordron, Anne, additional, Zdrenghea, Mihnea, additional, Cristea, Victor, additional, Douet-Guilbert, Nathalie, additional, and Renaudineau, Yves, additional
Published: 2017
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149. Alterations in DNA methylation/demethylation intermediates predict clinical outcome in chronic lymphocytic leukemia

Author: Bagacean, Cristina, primary, Tempescul, Adrian, additional, Le Dantec, Christelle, additional, Bordron, Anne, additional, Mohr, Audrey, additional, Saad, Hussam, additional, Olivier, Valerie, additional, Zdrenghea, Mihnea, additional, Cristea, Victor, additional, Cartron, Pierre-François, additional, Douet-Guilbert, Nathalie, additional, Berthou, Christian, additional, and Renaudineau, Yves, additional
Published: 2017
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150. FIRST LINE TREATMENT BY THE RIBVD REGIMEN ELICITS HIGH CLINICAL AND MOLECULAR RESPONSE RATES AND PROLONGED SURVIVAL IN ELDERLY MCL PATIENTS; FINAL RESULTS OF a LYSA GROUP TRIAL

Author: Gressin, R., primary, Daguindau, N., additional, Tempescul, A., additional, Moreau, A., additional, Carras, S., additional, Cartron, G., additional, Schmitt, A., additional, Houot, R., additional, Dartigeas, C., additional, Pignon, J., additional, Corm, S., additional, Bannos, A., additional, Mounier, C., additional, Dupuis, J., additional, Macro, M., additional, Fleury, J., additional, Jardin, F., additional, Karlin, L., additional, Damaj, G., additional, Feugier, P., additional, Fornecker, L., additional, Chabrot, C., additional, Ysebaert, I., additional, Callanan, M., additional, and Le Gouill, S., additional
Published: 2017
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