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1. Rapid and complete response to idelalisib in a case of Richter syndrome

Author: Christian Berthou, Cristina Bagacean, Hussam Saad, Mihnea Zdrenghea, Adrian Tempescul, and Yves Renaudineau
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Chronic lymphocytic leukemia, Aggressive lymphoma, Malignancy, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Chemoimmunotherapy, hemic and lymphatic diseases, Internal medicine, medicine, Pharmacology (medical), Prospective cohort study, B cell, business.industry, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, Idelalisib
Abstract: Richter syndrome (RS) is an aggressive lymphoma arising on the back of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and is the most common B-cell malignancy in the Western world. In the majority of cases, RS presents an activated B cell (ABC) phenotype of diffuse large B-cell lymphoma (DLBCL). From the therapeutic point of view, selective inhibition of PI3Kδ with idelalisib represents a valuable addition to available treatment options for patients with CLL/SLL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. However, to our knowledge, there have been no prospective studies evaluating idelalisib efficacy in a DLBCL-ABC form of RS. Here, we present a case of a DLBCL-ABC form of RS achieving a complete response at 3 weeks after initiating idelalisib and rituximab therapy for six cycles. This response was maintained during the idelalisib monotherapy, but the patient relapsed rapidly after treatment was withdrawn, because of a grade three immune colitis that developed at 10 months of treatment. This report demonstrates that idelalisib is highly effective in RS and provides an attractive option in this aggressive disease. This agent could meet an unmet need by providing a treatment option with a tolerable safety profile for elderly patients with RS.
Published: 2019
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2. Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: an LOC network study

Author: Gandhi Damaj, Khê Hoang-Xuan, Emmanuel Gyan, Marion Lam, Laurent Meyer, Magali Sampo, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Remy Gressin, Caroline Houillier, Adrien Chauchet, Jérôme Tamburini-Bonnefoy, Laurent Kodjikian, Marie-Laure Le Lez, Lucie Oberic, Roch Houot, Christelle Schneider, Sarra Gattoussi, Hélène Massé, Béatrice Cochener, Jean-Claude Quintyn, Nathalie Cassoux, Priscille Ollé, Karine Angioi-Duprez, Luc-Matthieu Fornecker, Carole Soussain, Jean-Pierre Marolleau, Guido Ahle, Marie-Pierre Moles, Christophe Chiquet, Claire Schwartz, Marie Blonski, Fabien Croisé, Valérie Touitou, Laurent Ballonzoli, Frédéric Mouriaux, Hervé Ghesquières, Bahram Bodaghi, Adrian Tempescul, Magali Le Garff-Tavernier, Emeline Tabouret, Eve Rousseau, Paul Franciane, Benjamin Jany, Antoine P. Brézin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Institut Curie [Paris], Université de Paris (UP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ophtalmologie [Hôpital de la Timone - APMH], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 ), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital pasteur [Colmar], CHU Grenoble, 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), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Clermont-Ferrand, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Strasbourg, Institut de neurosciences translationnelles de Paris (NeurATRIS - IHU-A-ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), None, Université Paris Cité (UPCité), 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 ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chard-Hutchinson, Xavier, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, medicine.medical_treatment, Retinal Neoplasms, [SDV]Life Sciences [q-bio], Population, Disease, Systemic therapy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Intraocular Lymphoma, Internal medicine, medicine, Humans, education, Aged, Aged, 80 and over, Chemotherapy, education.field_of_study, business.industry, Hematology, Middle Aged, Prognosis, High dose methotrexate, 3. Good health, [SDV] Life Sciences [q-bio], Methotrexate, Treatment Outcome, 030220 oncology & carcinogenesis, Toxicity, 030221 ophthalmology & optometry, Administration, Intravenous, Female, business, medicine.drug, Vitreoretinal lymphoma
Abstract: International audience; The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011-2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 41/59 (69%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.
Published: 2021
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3. MicroRNAs Associated With a Good Prognosis of Acute Myeloid Leukemia and Their Effect on Macrophage Polarization

Author: Alexandra Neaga, Cristina Bagacean, Adrian Tempescul, Laura Jimbu, Oana Mesaros, Cristina Blag, Ciprian Tomuleasa, Corina Bocsan, Mihaela Gaman, Mihnea Zdrenghea, Department of Hematology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of Pediatrics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, Department of Hematology, Ion Chiricuta Oncology Insitute, 'Ion Chiricuta' Cancer Institute, Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, Department of Hematology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, and Michel, Geneviève
Subjects: lcsh:Immunologic diseases. Allergy, MESH: Cell Differentiation, [SDV.IMM] Life Sciences [q-bio]/Immunology, macrophage polarization, tumor suppressor microRNA, Immunology, Macrophage polarization, Review, acute myeloid leukemia, MESH: Prognosis, Epigenesis, Genetic, Th2 Cells, MESH: Th2 Cells, microRNA, Animals, Humans, Immunology and Allergy, Medicine, MESH: Animals, MESH: Epigenesis, Genetic, Regulation of gene expression, MESH: Cytokines, Tumor microenvironment, MESH: Humans, business.industry, Macrophages, macrophages (M1/M2), MESH: Macrophages, Cancer, Myeloid leukemia, Cell Differentiation, MESH: Gene Expression Regulation, Neoplastic, Th1 Cells, Prognosis, medicine.disease, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute, MicroRNAs, Haematopoiesis, Leukemia, MESH: Th1 Cells, Cancer research, Cytokines, non-coding RNAs, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC581-607, MESH: Leukemia, Myeloid, Acute, business, MESH: MicroRNAs
Abstract: International audience; Acute myeloid leukemia (AML) is an aggressive myeloid malignancy with poor outcomes despite very intensive therapeutic approaches. For the majority of patients which are unfit and treated less intensively, the prognosis is even worse. There has been unspectacular progress in outcome improvement over the last decades and the development of new approaches is of tremendous interest. The tumor microenvironment is credited with an important role in supporting cancer growth, including leukemogenesis. Macrophages are part of the tumor microenvironment and their contribution in this setting is increasingly being deciphered, these cells being credited with a tumor supporting role. Data on macrophage role and polarization in leukemia is scarce. MicroRNAs (miRNAs) have a role in the post-transcriptional regulation of gene expression, by impending translation and promoting degradation of messenger RNAs. They are important modulators of cellular pathways, playing major roles in normal hematopoietic differentiation. miRNA expression is significantly correlated with the prognosis of hematopoietic malignancies, including AML. Oncogenic miRNAs correlate with poor prognosis, while tumor suppressor miRNAs, which inhibit the expression of proto-oncogenes, are correlated with a favorable prognosis. miRNAs are proposed as biomarkers for diagnosis and prognosis and are regarded as therapeutic approaches in many cancers, including AML. miRNAs with epigenetic or modulatory activity, as well as with synergistic activity with chemotherapeutic agents, proved to be promising therapeutic targets in experimental, pre-clinical approaches. The clinical availability of emerging compounds with mimicking or suppressor activity provides the opportunity for future therapeutic targeting of miRNAs. The present paper is focusing on miRNAs which, according to current knowledge, favorably impact on AML outcomes, being regarded as tumor suppressors, and reviews their role in macrophage polarization. We are focusing on miRNA expression in the setting of AML, but data on correlations between miRNA expression and macrophage polarization is mostly coming from studies involving normal tissue.
Published: 2021
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4. Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011)

Author: Roch Houot, Emmanuelle Nicolas Virelizier, Jehan Dupuis, Magda Alexis, Virginie De Wilde, Luc-Matthieu Fornecker, Julien Lazarovici, Marc André, Franck Morschhauser, David Sibon, Judith Racapé, Hervé Ghesquières, Anne-Claire Gac, Delphine Pranger, Hannah Moatti, Isabelle Demeestere, Hervé Maisonneuve, Julie Dechene, Adrian Tempescul, René-Olivier Casasnovas, Mohamed Touati, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
Subjects: Oncology, Adult, Anti-Mullerian Hormone, Male, Cancer Research, medicine.medical_specialty, endocrine system, Dacarbazine, Bleomycin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Testis, medicine, Humans, Doxorubicin, In patient, Prospective Studies, Etoposide, 030219 obstetrics & reproductive medicine, business.industry, Ovary, Recovery of Function, Hodgkin Disease, Vinblastine, Regimen, chemistry, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, medicine.drug
Abstract: PURPOSE The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) in early responders on the basis of a positron emission tomography (PET)–driven strategy was safe and minimized toxicity compared with standard 6 BEACOPPescalated cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old. METHODS Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up. RESULTS A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; P = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, P = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPPescalated group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; P < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; P = .004). CONCLUSION Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.
Published: 2021

5. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Author: Margaret Macro, Andrew Ar Belch, Antoine Tinel, Nathalie Meuleman, Jean Yves Mary, Christian Rose, Paula Rodriguez-Otero, Philippe Moreau, Wenming Chen, Michel Attal, Marie Lorraine Chretien, William Renwick, Kihyun Kim, Meletios A. Dimopoulos, Eileen M Boyle, Xavier Leleu, Michael Sturniolo, Thierry Facon, Heinz Ludwig, Mara Silvia Monzini, Vanessa Houck, Elena Zamagni, Adrian Tempescul, Salomon Manier, Cyrille Hulin, Shien Guo, Mohamad Mohty, Bruno M. Costa, Facon T., Dimopoulos M.A., Meuleman N., Belch A., Mohty M., Chen W.-M., Kim K., Zamagni E., Rodriguez-Otero P., Renwick W., Rose C., Tempescul A., Boyle E., Manier S., Attal M., Moreau P., Macro M., Leleu X., Lorraine Chretien M., Ludwig H., Guo S., Sturniolo M., Tinel A., Silvia Monzini M., Costa B., Houck V., Hulin C., Yves Mary J., CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, National and Kapodistrian University of Athens (NKUA), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Cross Cancer Institute [Edmonton, AB, Canada], Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Capital Medical University, Beijing, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Azienda Ospedaliero-Universitaria, Universidad de Navarra [Pamplona] (UNAV), Western Health The University of Melbourne, Université catholique de Lille (UCL), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Hôpital Universitaire de Caen, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Wilhelminenspital Vienna, Evidera, Celgene Corporation, Celgene International, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Wilhelminenspital Vienna = Wilhelminen Hospital
Subjects: 0301 basic medicine, Male, Cancer Research, [SDV]Life Sciences [q-bio], Dexamethasone, 0302 clinical medicine, Clinical trials, Multiple myeloma, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Lenalidomide, Melphalan, Aged, 80 and over, Frailty, Hematology, Middle Aged, 3. Good health, Thalidomide, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Haematological diseases, Human, Adult, medicine.medical_specialty, FIRST (MM-020) trial, Frail Elderly, Newly diagnosed, Transplant ineligible, Anesthésiologie, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Adverse effect, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Clinical trial, Cancérologie, 030104 developmental biology, Charlson comorbidity index, Prednisone, business, Hématologie
Abstract: Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS–containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019
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6. A case of IgE myeloma transformed into IgE-producing plasma cell leukaemia

Author: Jean-Richard Eveillard, Hélène Kerspern, Eric Lippert, Nicolas Galakhoff, Cyril Leven, Jean-Luc Carré, Maël Padelli, Caroline Buors, Cécile Aubron, Adrian Tempescul, Laboratoire de Biochimie (BREST - Biochimie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), 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), Unité de soins intensifs [Brest], Laboratoire d'hématologie (Labo Hémato - BREST), INSERM U1078, Université de Brest (UBO), and Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
Subjects: 0301 basic medicine, Immunofixation, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Case Reports, Immunoglobulin light chain, Immunoglobulin E, immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, Gammopathy, medicine, Multiple myeloma, biology, medicine.diagnostic_test, business.industry, immunofixation, Biochemistry (medical), monoclonal gammopathy of undetermined significance, multiple myeloma, plasma cell leukaemia, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Serum protein electrophoresis, Monoclonal, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Monoclonal gammopathy of undetermined significance
Abstract: International audience; This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgE-producing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagnosed due to an increase of the free kappa/lambda light chains ratio. No monoclonal immunoglobulin was detected by either serum protein electrophoresis (Capillarys 2, Sebia, Issy-les-Moulineaux, France) or immunofixation (Hydrasys 2, Sebia, Issy-les-Moulineaux, France). In June 2018, a blood smear led to the diagnosis of plasma cell leukaemia. A monoclonal peak was detected and identified as IgE-kappa. Analysis of an archival sample taken three years earlier, revealed the presence of a monoclonal IgE, which had been missed at diagnosis. Chemotherapy with bortezomib and dexamethasone was introduced. The patient survived 10 months after the diagnosis of leukaemia. This case shows that an abnormal free light chain ratio should be considered as a possible marker of IgE monoclonal gammopathy even in the absence of a solitary light chain revealed by immunofixation. In addition, the use of an undiluted serum may increase the sensitivity of the immunofixation for the detection of IgE monoclonal gammopathies compared to the 1:3 dilution recommended by the manufacturer.
Published: 2020
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7. 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: Stéphane Giraudier, Jean-Richard Eveillard, Christelle Le Gall-Ianotto, Ronan Le Calloch, Eric Lippert, Jean-Christophe Ianotto, Valérie Ugo, Karine Lacut, Morgane Abiven, Emmanuel Nowak, Gaelle Guillerm, Florence Dalbies, Adrian Tempescul, Christian Berthou, Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne et Maladies Infectieuses Quimper, 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 de Neurosciences de Brest (LNB), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université d'Angers (UA), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'hématologie (Labo Hémato - BREST), Laboratoire d'hématologie, CHU Bordeaux [Bordeaux], Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Laboratoires de Intéractions Epithéliums-Neurones, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Article, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, Fibrinolytic Agents, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Surveys and Questionnaires, hemic and lymphatic diseases, Internal medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Antithrombotic, Humans, Medicine, Polycythemia Vera, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Myeloproliferative Disorders, business.industry, Essential thrombocythemia, Incidence (epidemiology), Age Factors, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Thrombosis, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Pill, Concomitant, Female, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Thrombocythemia, Essential, 030215 immunology
Abstract: The purpose of this study was to identify the incidence, causes and impact of non-adherence to oral and subcutaneous chronic treatments for patients with polycythemia vera or essential thrombocythemia. Patients receiving cytoreductive drugs for polycythemia vera or essential thrombocythemia were recruited at our institution (Observatoire Brestois des Néoplasies Myéloprolifératives registry). They completed a one-shot questionnaire designed by investigators (Etude de l’Observance Thérapeutique et des Effets Secondaires des Traitements study). Data about complications (thrombosis, transformation and death) at any time in the patient’s life (before diagnosis, up until consultation and after the completion of the questionnaire) were collected. Sixty-five (22.7%) of 286 patients reported poor adherence (
Published: 2017
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8. Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies

Author: Mihnea Zdrenghea, Corina Bocsan, Cristina Ilcus, Cristian Popescu, Mihai Cenariu, Cristina Bagacean, Andrada Parvu, Adrian Tempescul, Department of Hematology, Cluj-Napoca, University of Medicine and Pharmacy, Luliu-Hatieganu, 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), LabEX IGO Immunothérapie Grand Ouest, Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan, Computer Science Department [Bucarest], University Politehnica of Bucharest [Romania] (UPB), Biotechnology Research Center, Roumanie, University of Agricultural Sciences and Veterinary Medicine, Roumanie, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, and 'Prof. Dr. Ion Chiricuta' Oncologic Insitute Cluj-Napoca
Subjects: 0301 basic medicine, Chronic lymphocytic leukemia, b7 antigens, lymphoma, Review, hematological cancer, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Pharmacology (medical), Lung cancer, Effector, business.industry, Cancer, immune checkpoint blockade, medicine.disease, Immune checkpoint, 3. Good health, Lymphoma, 030104 developmental biology, Oncology, programmed cell death 1, 030220 oncology & carcinogenesis, Immunology, Cancer cell, [SDV.IMM]Life Sciences [q-bio]/Immunology, chronic lymphocytic leukemia, business
Abstract: International audience; 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.
Published: 2017

9. First Results of the Acsé Pembrolizumab Phase II in the Primary CNS Lymphoma (PCNSL) Cohort

Author: Fabrice Jardin, Pierre Bories, Julie Abraham, Caroline Houillier, Nadine Martin-Duverneuil, Adrian Tempescul, Roch Houot, Chantal Campello, Philippe Agape, Clotilde Simon, Frédéric Legrand, Ophelie Querel, Natalie Hoog Labouret, Frederic Peyrade, Marie Blonski, Khê Hoang-Xuan, Emmanuel Gyan, Vincent Delwail, Hervé Ghesquières, Valérie Touitou, Sylvain Choquet, Gandhi Damaj, Philippe Rey, Sylvie Chevret, Christophe Massard, Nathalie Cassoux, Carole Soussain, Nathalie Baize, Anna Schmitt, Assia Lamrani-Ghaouti, and Guido Ahle
Subjects: Oncology, medicine.medical_specialty, Primary CNS Lymphoma, business.industry, Internal medicine, Immunology, Cohort, medicine, Cell Biology, Hematology, Pembrolizumab, business, Biochemistry
Abstract: Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with advanced rare cancers (NCT03012620). Here, we report the first results of Pembrolizumab in the cohort of Primary Central Nervous System Lymphoma (PCNSL). Methods: Main inclusion criteria were: relapsed or refractory PCNSL after one or several lines of treatment including high dose Methotrexate based chemotherapy, pathologically confirmed diffuse large B cell lymphoma, age>18, HIV negative, concurrent steroid medication at a dose no greater than prednisone 20 mg/day or equivalent. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycles for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to IPCG at 84 day after the start of treatment. Secondary endpoints included best response (ORR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. Analysis used all enrolled patients. Results: 50 patients suffering from PCNSL, including 9 primary vitreoretinal lymphoma (PVRL) were included from July, 2017 to October, 2019. Median age was 72 years (range: 43 to 83), Median PS (ECOG) was 1 (range 0-1). The median number of cycles was 4 (range 1-35). At 84 days from start of treatment, 6 patients responded (4 CR+2PR). Overall, 3 patients whose response was not assessed were considered as failures, and the rates of ORR (CR+PR), stable disease (SD), progressive disease (PD) were 26% (13/50, 8 CR + 5 PR), 10% (5/50), 58% (29/50), respectively. ORR was 29% (12/41) and 11% (1/9) in primary cerebral lymphoma and PVRL respectively. After a median follow-up of 6.7 months (range 0.2-27.4), median PFS was 2.6 months, with 6-month PFS of 29.8% and 6-month OS of 60.4%. In responders, median duration of response was estimated at 10 months (95%CI, 2.7 to 12.5). Grade III and IV toxicities related to the drug were observed in 4 patients (8%) and one patient (2%) respectively. No related toxic death was reported. Conclusion: Pembrolizumab shows moderate activity in relapsed/ refractory PCNSL with acceptable toxicity, supporting further studies evaluating its use in combination therapies. Disclosures Hoang-Xuan: BTG: Consultancy, Research Funding. Houot:Bristol-Myers Squibb: Honoraria; MSD: Honoraria; Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Schmitt:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen: Honoraria. Ahle:Roche: Honoraria; Novartis: Honoraria; Biogene: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria. Bories:Abbvie: Consultancy; Celgen: Consultancy; Gilead: Consultancy; BMS: Honoraria; Novartis: Honoraria. Houillier:BTG: Consultancy.
Published: 2020
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10. Prognostic Value of Baseline Total Metabolic Tumor Volume Measured on FDG PET in Patients With Richter Syndrome

Author: Clémence Pontoizeau, Thierry Lamy, Florence Le Jeune, Habiba Mesbah, Laure-Anne Haumont, Adrian Tempescul, Xavier Palard-Novello, Antoine Girard, Anne Devillers, Pierre-Yves Salaun, CRLCC Eugène Marquis (CRLCC), Département de médecine nucléaire [Rennes], Centre Hospitalier Universitaire [Rennes], CHRU Brest - Service de médecine nucléaire (CHU - BREST - Med Nucléaire), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Multivariate analysis, Chronic lymphocytic leukemia, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, immune system diseases, Fluorodeoxyglucose F18, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Stage (cooking), neoplasms, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Univariate analysis, Performance status, business.industry, General Medicine, Metabolic tumor volume, Middle Aged, medicine.disease, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Lymphoma, Tumor Burden, Cell Transformation, Neoplastic, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, 030220 oncology & carcinogenesis, Multivariate Analysis, Female, Lymphoma, Large B-Cell, Diffuse, business, Glycolysis
Abstract: PURPOSE We evaluated the prognostic value of baseline total metabolic tumor volume (TMTV) measured using pretreatment FDG PET for patients with transformation of chronic lymphocytic leukemia (CLL) into diffuse large B-cell lymphoma (DLBCL). METHODS A total of 28 patients with transformation of CLL into DLBCL who had undergone FDG PET before treatment were retrospectively reviewed. Univariate and multivariate analysis of conventional clinicopathologic variables (sex, age, World Health Organization performance status score, International Prognostic Index score, Binet stage, lactate dehydrogenase serum level [LDH], platelet count, presence or not of prior therapies for CLL, the time from CLL to Richter syndrome, Ann Arbor stage, Bulky or not) and metabolic parameters (SUVmax, SUVmean, TMTV, and total lesion glycolysis) at the time of the transformation of CLL into DLBCL were tested for overall survival (OS). RESULTS Of the 28 patients, 14 patients (50%) died during the follow-up period. Low platelet count, World Health Organization performance status score >1, high LDH, and high TMTV were found to be significant prognostic factors for OS on univariate analysis. The 5-year estimates of OS were 63% in the low metabolic burden group (TMTV ≤1200 cm) and 0% in the high metabolic burden group (TMTV >1200 cm). Multivariate analysis revealed that only high LDH was a significant predictor after adjustment for other variables of OS. CONCLUSIONS TMTV extracted from FDG PET at the time of the transformation of CLL into DLBCL is a predictor of OS.
Published: 2019
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11. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation

Author: Diane Damotte, Remy Dulery, Olivier Casasnovas, Caroline Regny, Lysa, Guillaume Manson, Adrien Chauchet, Georges Garnier, Emmanuelle Nicolas-Virelizier, Aspasia Stamatoullas, Jean-Marc Schiano, Krimo Bouabdallah, Hervé Ghesquières, Charles Herbaux, Jean-Baptiste Mear, Roch Houot, Marie-Pierre Moles-Moreau, Pauline Brice, Adrian Tempescul, Alain Delmer, Bénédicte Deau, Anna Schmitt, Laurent Dercle, Cécile Borel, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département Hématologie (FNCLCC), Centre Léon Bérard [Lyon], 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 Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Hématologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Columbia University Medical Center (CUMC), Columbia University [New York], Hopital Saint-Louis [AP-HP] (AP-HP), 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 ), Bristol-Myers SquibbBristol-Myers Squibb, 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), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), CCSD, Accord Elsevier, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, 0302 clinical medicine, Antineoplastic Agents, Immunological, Risk Factors, Anti pd1, ComputingMilieux_MISCELLANEOUS, Allogenic haematopoietic stem cell transplantation, Hematopoietic Stem Cell Transplantation, Middle Aged, Hodgkin Disease, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, Nivolumab, 030220 oncology & carcinogenesis, Disease Progression, Female, France, Immunotherapy, Stem cell, Checkpoint inhibitors, Adult, medicine.medical_specialty, Adolescent, Risk Assessment, 03 medical and health sciences, Young Adult, Refractory, Internal medicine, medicine, Humans, Transplantation, Homologous, Aged, Retrospective Studies, Anti-PD1, business.industry, Transplantation, 030104 developmental biology, Hodgkin lymphoma, business
Abstract: Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL).We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT.After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT.Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.
Published: 2019
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12. Complement System: a Neglected Pathway in Immunotherapy

Author: Adrian Tempescul, Anne Bordron, Yves Renaudineau, Cristina Bagacean, Sophie Hillion, Christian Berthou, Eléonore Bettacchioli, 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), Laboratoire d'Immunologie et Immunothérapie [Brest], and Laboratoire d'Immunologie et Immunothérapie
Subjects: 0301 basic medicine, Monoclonal antibody, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Complement Pathway, Alternative, Complement, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Animals, Humans, Immunologic Factors, Complement Pathway, Classical, Cytotoxicity, Complement Activation, 030203 arthritis & rheumatology, Mutation, business.industry, Antibodies, Monoclonal, General Medicine, Immunotherapy, Complement System Proteins, In vitro, 3. Good health, Complement (complexity), Complement system, 030104 developmental biology, Treatment Outcome, Mechanism of action, Cancer research, Autoimmunity cancer, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business, Biomarkers
Abstract: International audience; Approved for the treatment of autoimmune diseases, hematological malignancies, and solid cancers, several monoclonal antibodies (mAb) make use of complement in their mechanism of action. Such an assessment is based on comprehensive investigations that used mouse models, in vitro studies, and analyses from patients at initiation (basal level to highlight deficiencies) and after treatment initiation (mAb impact on complement), which have further provided key insights into the importance of the complement activation and/or complement deficiencies in mAb activity. Accordingly, new approaches can now be developed with the final objective of increasing the clinical efficacy of mAb. These improvements include (i) the concurrent administration of fresh frozen plasma during mAb therapy; (ii) mAb modifications such as immunoglobulin G subclass switching, Fc mutation, or IgG hexamerization to improve the fixation and activation of C1q; (iii) optimization of the target recognition to induce a higher complement-dependent cytotoxicity (CDC) and/or complement-dependant cellular cytotoxicity (CDCC); and (iv) the control of soluble and cellular complement inhibitors.
Published: 2019
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13. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study

Author: Daniel Delgadillo, Carole Soussain, Bachir Aidaoui, Eileen M Boyle, Philippe Agapé, Vincent Delwail, Agusti Alentorn, Adrien Chauchet, Olivier Casasnovas, Hassen Douzane, Franck Morschhauser, Magali Le Garff-Tavernier, Marie Blonski, Olivier Chinot, Luc Taillandier, Matthieu Peyre, Myrto Costopoulos, Chantal Campello, Fabrice Jardin, Jerome Tamburini, Aurélie Kas, Alexandra Amiel, Frédéric Charlotte, Michel Fabbro, Karima Mokhtari, Emeline Tabouret, Caroline Houillier, Valérie Touitou, Agathe Waultier, Jacques-Olivier Bay, Gandhi Damaj, Nadine Martin-Duverneuil, Lucie Oberic, Julie Abraham, Roch Houot, Hervé Ghesquières, Marie-Pierre Moles-Moreau, Remy Gressin, Corinne Haioun, Adrian Tempescul, Diane Genet, Thierry Lamy, Safia Chebrek, Philippe Colin, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Jean-Pierre Marolleau, Guido Ahle, Loïc Feuvret, Luc-Matthieu Fornecker, Khê Hoang-Xuan, Emmanuel Gyan, Kamel Laribi, Bertrand Mathon, Caroline Serrier, Pierre Soubeyran, Nathalie Cassoux, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), 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 ), CHU Pontchaillou [Rennes], CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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 ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, medicine.medical_specialty, Antimetabolites, Antineoplastic, Palliative care, Adolescent, Databases, Factual, Lymphoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Article, Central Nervous System Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, hemic and lymphatic diseases, Outcome Assessment, Health Care, medicine, Humans, Progression-free survival, Young adult, education, Aged, Retrospective Studies, education.field_of_study, business.industry, Age Factors, Retrospective cohort study, Middle Aged, Combined Modality Therapy, Progression-Free Survival, 3. Good health, Transplantation, Clinical trial, Methotrexate, 030220 oncology & carcinogenesis, Rituximab, Neurology (clinical), France, Cranial Irradiation, business, 030217 neurology & neurosurgery, medicine.drug, Stem Cell Transplantation
Abstract: ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients 60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.
Published: 2019
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14. 17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia

Author: Yves Renaudineau, Anne Banet, Gilles Paintaud, David Ternant, Nathalie Douet-Guilbert, Boutahar Bendaoud, Adrian Tempescul, Anne Bordron, Cristina Bagacean, Mihnea Zdrenghea, Christian Berthou, Hussam Saad, 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), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Génétique moléculaire et génétique épidémiologique, Laboratoire d'Immunologie et Immunothérapie [Brest], Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 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), Université de Brest (UBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Tours
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, Antineoplastic Agents, Immunological, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Immunology and Allergy, Molecular Targeted Therapy, Aged, 80 and over, Anti-CD20 monoclonal antibody, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 17p deletion, Chemotherapy regimen, 3. Good health, Fludarabine, [SDV] Life Sciences [q-bio], Leukemia, 030220 oncology & carcinogenesis, Clearance, Molecular Medicine, Female, Rituximab, Chromosome Deletion, IGHV@, medicine.drug, Adult, Bendamustine, medicine.medical_specialty, Cyclophosphamide, Immunology, Short Report, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, medicine, Humans, Pharmacokinetics, Aged, Neoplasm Staging, Pharmacology, business.industry, Genetic Variation, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 030104 developmental biology, Tumor Suppressor Protein p53, business, Chromosomes, Human, Pair 17
Abstract: International audience; Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)). This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study. Accordingly, 44 CLL patients were included in the study, and among them 9 presented a del(17p). Next, a total of 233 rituximab sera were selected for a pharmacokinetic study and analyzed in a two-compartment model showing important differences when del(17p) CLL patients were compared with non-del(17p) patients treated with rituximab and chemotherapy: (1) clearance of rituximab was faster; (2) central volume of rituximab distribution V1 (peripheral blood) was reduced while peripheral volume V2 (lymphoid organs and tissues) was increased; and (3) the rate of rituximab elimination (Kout) was faster. In contrast, the group with a better prognosis harboring isolated del(13q) presented a slower rate of elimination (Kout). Pharmacokinetic parameters were independent from the other factors tested such as age, sex, chemotherapy regimen (fludarabine/cyclophosphamide versus bendamustine), IGHV mutational status, and FCGR3A 158VF status. In conclusion, this study provides an additional argument to consider that del(17p) is effective not only to control chemoresistance but also monoclonal antibody activity, based on higher rituximab turnover.
Published: 2019
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15. Relapsed or refractory chronic lymphocytic leukemia retreated with rituximab in daily practice: final results of the PERLE study

Author: Eric Jourdan, Kalaivani Veerabudun, Brigitte Dreyfus, Yazid Arkam, Chahinez Benkanoun, Sylvain Choquet, Alain Delmer, Abdelaziz Chaib, Sophie Gandon, Kun Lun Liu, Lionel Karlin, Olivier Fitoussi, Stéphane Leprêtre, H. Orfeuvre, Marc Maynadié, Marie-Sarah Dilhuydy, Omar Benbrahim, Frédéric Boissard, Borhane Slama, Adrian Tempescul, Jean Luc Labourey, Driss Chaoui, Laurent Voillat, Maya Hacini, Laurence Sanhes, Marly Barry, and Beatrice Mahe
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Chronic lymphocytic leukemia, Kaplan-Meier Estimate, Antineoplastic Agents, Immunological, immune system diseases, Recurrence, hemic and lymphatic diseases, Internal medicine, Daily practice, medicine, Humans, Multicenter Studies as Topic, neoplasms, business.industry, Hematology, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Treatment Outcome, Drug Resistance, Neoplasm, Retreatment, Rituximab, Female, France, Refractory Chronic Lymphocytic Leukemia, business, medicine.drug
Abstract: Chronic lymphocytic leukemia (CLL) is the most prevalent type of adult leukemia in Western countries [1]. Despite advances in chemo-immunotherapy, most CLL patients relapse after the first-line che...
Published: 2019

16. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

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

Author: Christian Berthou, Gaelle Guillerm, Jean-Christophe Ianotto, Pascal Delépine, Chloé Henry, Caroline Buors, Christophe Nicol, Marie-Anne Couturier, Céline Tripogney, Adrian Tempescul, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang Bretagne, EFS, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'hématologie (Labo Hémato - BREST), 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), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), 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), Michel, Geneviève, Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Male, Oncology, Drug, Cancer Research, medicine.medical_specialty, Filgrastim, [SDV.IMM] Life Sciences [q-bio]/Immunology, media_common.quotation_subject, Treatment outcome, Neutropenia, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Biosimilar Pharmaceuticals, Internal medicine, Granulocyte Colony-Stimulating Factor, medicine, Humans, ComputingMilieux_MISCELLANEOUS, media_common, Postoperative Care, business.industry, Hematopoietic Stem Cell Transplantation, Biosimilar, Hematology, medicine.disease, Recombinant Proteins, 3. Good health, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Multiple Myeloma, business, 030215 immunology, medicine.drug
Abstract: RhuG-CSF reduces the duration of neutropenia induced by chemotherapies. The most frequent drug used for this indication is filgrastim (initially Neupogen®-AMGEN SA). Filgrastim biosimilars have bee...
Published: 2017
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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. 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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27. 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

28. 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

29. 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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30. 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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31. 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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32. 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

33. 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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34. 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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35. 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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36. ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

Author: Cristina Bagacean, Mihnea Zdrenghea, Adriana Muresan, Christian Berthou, Doinel Radeanu, Rodica Ungur, Adrian Tempescul, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 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), and LabEX IGO Immunothérapie Grand Ouest
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, OncoTargets and Therapy, Internal medicine, medicine, Autologous transplantation, Pharmacology (medical), platinum, Etoposide, PCNSL, Original Research, Chemotherapy, Ifosfamide, business.industry, Primary central nervous system lymphoma, Lomustine, medicine.disease, 3. Good health, relapsed, refractory, Immunology, cerebral lymphoma, Cytarabine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, ESHAP, medicine.drug
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

37. Ofatumumab capacity to deplete B cells from chronic lymphocytic leukaemia is affected by C4 complement exhaustion

Author: Marjolaine Debant, Cristina Bagacean, Sophie Hillion, B. Bendaoud, Yves Renaudineau, Catherine Riou, Caroline Buors, Christian Berthou, Adrian Tempescul, 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), LabEX IGO Immunothérapie Grand Ouest, Modélisation, Intelligence, Processus et Système (MIPS), Université de Haute Alsace - Mulhouse : EA2332, Laboratoire d'Immunologie et Immunothérapie, and Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL)
Subjects: 0301 basic medicine, Male, MESH: Combined Modality Therapy, Lymphocytosis, Cell, MESH: Antibodies, Monoclonal, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, MESH: Child, hemic and lymphatic diseases, complement, Child, MESH: Leukemia, Lymphocytic, Chronic, B-Cell, MESH: Treatment Outcome, MESH: Aged, B-Lymphocytes, MESH: Middle Aged, biology, FcγRIII polymorphism, MESH: Complement C3, Antibodies, Monoclonal, MESH: Complement C4, Complement C4, Hematology, General Medicine, Complement C3, Middle Aged, MESH: Infant, Combined Modality Therapy, 3. Good health, medicine.anatomical_structure, Treatment Outcome, MESH: Young Adult, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Adult, MESH: Immunophenotyping, Adolescent, medicine.drug_class, Antineoplastic Agents, MESH: Receptors, IgG, Ofatumumab, Monoclonal antibody, Antibodies, Monoclonal, Humanized, CD19, Lymphocyte Depletion, Immunophenotyping, 03 medical and health sciences, Young Adult, MESH: B-Lymphocytes, MESH: Polymorphism, Genetic, medicine, Humans, Aged, MESH: Adolescent, MESH: Lymphocyte Depletion, MESH: Humans, Lymphocytic leukaemia, Polymorphism, Genetic, business.industry, MESH: Child, Preschool, Receptors, IgG, Infant, MESH: Adult, Leukemia, Lymphocytic, Chronic, B-Cell, MESH: Male, Complement system, 030104 developmental biology, chemistry, Immunology, MESH: Biomarkers, biology.protein, MESH: Antineoplastic Agents, CD5, business, MESH: Female, chronic lymphocytic leukaemia, ofatumumab, Biomarkers, 030215 immunology
Abstract: International audience; The management of patients with chronic lymphocytic leukaemia (CLL) has improved with the utilisation of ofatumumab as a novel anti-CD20 monoclonal antibody. However, as half of the patients fail to respond to the treatment, the aim of this study was to evaluate circulating CLL cell depletion and clinical response according to the context of complement activation and FcγRIIIA polymorphism in ten CLL patients with relapsed/refractory disease. At the end of the treatment, results indicated that circulating CD5(+) CD19(+) CLL cell depletion was major (50% decrease) in 4 of 10 patients and ineffective for the two other patients. No clinical modifications were observed following ofatumumab introduction. Ofatumumab administration leads to a rapid and important exhaustion of complement C4 levels in patients with initial lymphocytosis. C4 exhaustion was accelerated in a non-responder patient, and incomplete in two patients with partial circulating depletion. Moreover, delaying weekly to monthly ofatumumab injections improved CLL cell depletion in two patients. FcγRIIIA 158 polymorphism (FF n = 6 and VF n = 4) was not associated with major and/or partial circulating CLL cell depletion. In conclusion, ofatumumab induces an important C4 exhaustion that needs to be taken into account when treating CLL patients with ofatumumab.
Published: 2015

38. Imatinib mesylate induces massive and nonspecific aminoaciduria in cml patients

Author: Pauline Grall, Jean-Richard Eveillard, Christian Berthou, Adrian Tempescul, Yolande Amet, Gaelle Guillerm, Florence Dalbies, and Jean-Christophe Ianotto
Subjects: Imatinib mesylate, business.industry, Aminoaciduria, Cancer research, Medicine, Hematology, business, medicine.disease
Published: 2012
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39. Experience (1 year) of G-CSF biosimilars in PBSCT for lymphoma and myeloma patients

Author: J-R Eveillard, Christian Berthou, Pascal Delépine, J-C Ianotto, Gaelle Guillerm, N Mugnier, E. Hardy, X Yan, R. Le Calloc’h, and Adrian Tempescul
Subjects: Transplantation, business.industry, Biosimilar, Hematology, medicine.disease, Lymphoma, Graft-versus-host disease, Text mining, Immunology, medicine, Stem cell, Progenitor cell, business
Published: 2011
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40. Cytomegalovirus-associated meningoradiculoneuritis after treatment of mantle cell lymphoma with a combination of chemotherapy and rituximab

Author: A. Tran, M. C. Legrand-Quillien, S. Vallet, A. Tempescul, V. Narbonne, and C. Berthou
Subjects: Vincristine, medicine.medical_specialty, Chemotherapy, Chlorambucil, business.industry, medicine.medical_treatment, Hematology, General Medicine, medicine.disease, Gastroenterology, Lymphoma, medicine.anatomical_structure, hemic and lymphatic diseases, Internal medicine, medicine, Cytarabine, Mantle cell lymphoma, Rituximab, Bone marrow, business, medicine.drug
Abstract: Rituximab is a chimeric human/mouse monoclonal antibody directed against the CD20 antigen. It has become part of the standard therapy for non-Hodgkin’s lymphoma (NHL). Rituximab effectively kills lymphoma B cells and rapidly leads to the sustained depletion of peripheral blood B cells. Mantle cell lymphoma (MCL) is incurable with standard therapy. The median survival time is short (43 months). Rituximab has been shown to trigger a response in between 20 and 38% of patients with MCL [1]. Sustained rituximab-induced B-cell depletion may compromise the immune system. Accordingly, some viral infections have already been reported in patients with NHL receiving chemotherapy in conjunction with rituximab. Here, we describe an unusual case of cytomegalovirus reactivation in one patient with MCL who had previously been treated with chemotherapy plus rituximab. A57-year-oldmanwasdiagnosedwithcyclinD1-positive inguinal bilateral MCL, Ann Arbor stage II, in March 2003. Before the start of chemotherapy, gammaglobulinemia was normal (10 g/l). He was treated with VAD (vincristine 0.4 mg/day on days 1–4, doxorubicin 9 mg/m/day on days 1–4, dexamethasone 40 mg/day on days 1–4) plus chlorambucil (6 mg/day on days 20–29) and rituximab (375 mg/m on day 28) (5 cycles) for 6 months. This chemotherapy corresponds to the GroupeOuest Est d’etude des Leucemies et Autres Maladies du Sang (GOELAMS) MCL 2001 clinical research protocol, which includes six cycles of VAD– chlorambucil–rituximab followed by therapeutic intensification with total-body irradiation (TBI) plus busulfan before autologous peripheral stem cell reinjection. Before the beginning of the treatment, hypercellularity associated with elevated protein levels in cerebrospinal fluid (CSF) let us suppose neuromeningeal localisation. Thus, intrathecal infusions (nine cycles) with methylprednisolone (40 mg), cytarabine (40mg) and methotrexate (15 mg) were administered. In October 2003, he was referred for accentuated neuromuscular weakness and diffuse chest pain associated with a persistent headache (10 days) resistant to usual painkillers. Clinical examination revealed neurological deficit affecting the psoas territory and the foot and finger elevators. Osteotendinous reflexeswere abolished.Nopulmonary, cardiac or abdominal manifestations were observed. Whole-body computed tomography (CT) found an interstitial syndrome without adenopathy. Electromyography and nerve conduction analysis did not find any acute signs but revealed chronic anterior horn cell lesions. Bone marrow aspirate was normal. Peripheral blood contained atypical basophilic lymphocytes, suggestive of lymphocyte activation. C-reactive protein concentration was moderately elevated (33 g/l). Hypogammaglobulinemia (5 g/l) without monoclonal secretion was found. Blood and bone marrow were negative for cyclin D1. Fluorescent in situ hybridisation (FISH) analysis failed to detect t(11;14) translocation in the CSF. Hepatic and kidney functions were normal. Blood cultures were negative for bacteria. Serum was positive for cytomegalovirus (CMV) IgG with a high avidity, showing prior immunity. Electroencephalography (EEG) showed a focal lesion in the frontal and temporal regions, but no associated clinical phenotype was observed. CSF contained an abnormally high amount of protein (0.63 g/l) and normal glucose and chloride levels. The CSF contained 38 leukocytes/mm (65% lymphocytes, 9% monocytes and 25% polynuclear S. Vallet (*) . A. Tran . M. C. Legrand-Quillien . V. Narbonne Department of Microbiology (E.A. Biodiversity and Microbial Ecology no. 3882), University Hospital Morvan, 2 avenue Foch, 29609 Brest Cedex, France e-mail: sophie.vallet@chu-brest.fr Tel.: +33-2-98223308 Fax: +33-2-98223987
Published: 2005
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41. Severe CMV complication following maintenance therapy with rituximab

Author: Lenaïg Le Clech, Jean-Christophe Ianotto, Isabelle Quintin-Roué, and Adrian Tempescul
Subjects: Male, medicine.medical_treatment, Congenital cytomegalovirus infection, Cytomegalovirus, Antineoplastic Agents, Antibodies, Viral, Severity of Illness Index, Article, Antibodies, Monoclonal, Murine-Derived, Maintenance therapy, immune system diseases, hemic and lymphatic diseases, medicine, Humans, Aged, Chemotherapy, business.industry, virus diseases, General Medicine, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Monoclonal, Immunology, Cytomegalovirus Infections, Rituximab, business, Encephalitis, Rare disease, medicine.drug, Follow-Up Studies
Abstract: Cytomegalovirus (CMV) encephalitis is a rare infection that immunodeficient patients, mainly where HIV-positive, may suffer from. Several cases were described when complications with the treatment with monoclonal antibodies, like rituximab, for malignant lymphomas. We will describe here the case of a patient, who has developed CMV gastritis, then CMV encephalitis after the treatment of a CLL with a chemotherapy and maintenance therapy with rituximab.
Published: 2013

42. The French LOC Network for Primary CNS Lymphoma (PCNSL) Patients: What Can We Learn from a Large National Database?

Author: Olivier Chinot, Luc Fornecker, Valérie Touitou, Pierre Soubeyran, Adrian Tempescul, Luc Taillandier, Franck Morschhauser, Roch Houot, Vincent Delwail, Arnaud Jaccard, Philippe Agape, Marie-Pierre Moles, Cécile Chabrot, Nathalie Cassoux, Carole Soussain, Khê Hoang-Xuan, Emmanuel Gyan, Caroline Houillier, Michel Fabbro, Guido Ahle, Annie Brion, Sylvain Choquet, Olivier Casanovas, Remy Gressin, Herve Ghesquieres, Pascal Bourquard, Gandhi Damaj, and Fabrice Jardin
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, Palliative care, business.industry, Immunology, Primary central nervous system lymphoma, Induction chemotherapy, Cell Biology, Hematology, medicine.disease, Biochemistry, Chemotherapy regimen, 03 medical and health sciences, Regimen, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Rituximab, business, Diffuse large B-cell lymphoma, Progressive disease, medicine.drug
Abstract: Background The shared knowledge regarding management and outcome of PCNSL patients are usually based on results of clinical phase II studies that include limited series of selected patients, which imperfectly reflect the medical care in "real life". Methods The LOC network, certified by the national cancer institute (INCa), is a national network of expert centres for PCNSL. Since 2011, we are prospectively recording in the LOC database all newly diagnosed PCNSL patients from the 22 regional expert centres for PCNSL that cover the whole country. Data from PCNSL patients registered in the LOC database from January 2011 to March 18, 2016 were analyzed. Results Data from 971 patients were available in the LOC database at the time of analysis: sex ratio: 1.05, median age: 67 (18-92), median Karnofsky Performance Status: 60 (20-100), diffuse large B cell lymphoma: 97%, ocular involvement: 20%, cerebrospinal (CSF) involvement: 18%. Diagnosis procedure was biopsy (80%), tumor resection (9%), vitrectomy (8%), CSF cytology (3%). Treatment was initiated either by a neuro-oncology or a haematology team in 38% and 62%, respectively. Median delay between first symptoms and onset of treatment was 62 days. First line treatment was high-dose (HD) methotrexate (MTX) based chemotherapy (CT) (90%), other chemotherapy regimen (6%), or palliative care (4%). The use of Rituximab has gradually increased from 50 % of patients between 2011 and 2013, up to 87 % of patients in 2016. 16 % of patients were included in prospective trials. After first-line induction chemotherapy, responder patients < 60 years received a consolidation treatment in 75 % of cases consisting of either whole brain radiotherapy (WBRT) (49 %) or HD CT with autologous stem cell transplantation (HD CT-ASCT) (26 %). Low dose WBRT (23,4) is being used in younger CR patients since 2014. In responder patients > 60 years, WBRT was seldom given (9%) according to national guideline, and HD CT-ASCT was offered to 1% of patients. Response rates to first-line treatment among evaluable patients (n = 655) were: complete response: 59%; partial response: 10%; stable disease: 3%; progressive disease: 28%. Relapse occurred in 42 % patients < 60 y and in 62 % in older patients. At relapse, second line chemotherapy, HD CT-ASCT, WBRT and palliative care were offered in 50%, 18%, 12%, 20% of patients respectively. With a median follow-up of 20.4 months, median progression free survival (PFS) was 9.9 months for the whole population (< 60 years: 34.6 months; > 60 years: 7.9 months). Median overall survival (OS) and 5-year OS were 30 months and 41% respectively (< 60 years: not reached, 68%; > 60 years: 15 months, 30%). Conclusion The therapeutic practices in France reflect the current knowledge and controversies in PCNSL. Long-term survival has become frequent, especially among youngest patients who usually receive a consolidation treatment and to whom HD CT-ASCT can be offered at relapse. Relapse rate remains frequent and especially in elderly patients in whom consolidation treatment is omitted. Such an overview points out a couple of issues. Despite homogeneous treatments following national guidelines in accordance with the state of the art of medical care, standards of care are to be challenged, both for increasing the CR and decrease the relapse rates. The development of target and innovative therapies in PCNSL alone or in combinatorial regimen is needed. PFS and OS of patients according to age Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Soussain: Roche: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding. Ghesquieres:Mundipharma: Consultancy; Roche France: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Choquet:Janssen: Consultancy; Celgene: Consultancy. Morschhauser:Servier: Consultancy, Honoraria; Janssen: Honoraria; Gilead Sciences: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria.
Published: 2016
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43. Bendamustine-Based (BeEAM) Conditioning before Autologous Stem Cell Transplantation: Result of a French Multicenter Study of 386 Patients from Lysa Centers

Author: Anne-Claire Gac, Olivier Tournilhac, Ibrahim Yakoub-Agha, Benjamin Carpentier, Emmanuel Gyan, Sandra Malak, Caroline Delette, Eric Durot, Mohamed Amine Bekadja, Emmanuelle Tchernonog, Roch Houot, Momar Diouf, Thomas Gastinne, Adrien Chauchet, Sylvain Chantepie, Arnaud Jaccard, Marie-Virginie Larcher, Bachra Choufi, Ahmad Ibrahim, Rene-Olivier Casasnovas, Luc Mathieu Fornecker, Reda Garidi, Gandhi Damaj, Carole Soussain, Krimo Bouabdallah, Frederic Peyrade, Stéphanie Guidez, Jean-Pierre Vilque, Adrian Tempescul, and Remy Gressin
Subjects: Bendamustine, medicine.medical_specialty, Immunology, Biochemistry, Gastroenterology, Nephrotoxicity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autologous stem-cell transplantation, Intensive care, Internal medicine, Medicine, Creatinine, business.industry, Cell Biology, Hematology, medicine.disease, Surgery, Regimen, chemistry, 030220 oncology & carcinogenesis, Mantle cell lymphoma, business, Packed red blood cells, 030215 immunology, medicine.drug
Abstract: Unavailability of Carmustine and its dramatically increased cost by nearly 10 fold has led to its replacement by bendamustine (Be) and an increase use of Bendamustine-based (BeEAM) conditioning regimen before autologous stem cell transplantation for lymphoma. The aim of this study was to evaluate the safety of the BeEAM regimen in the real life use in several French centers. Median age of the 386 patients (233 male, 153 female) was 55 years (17-72). The majority of patients had aggressive B-cell (40%), follicular (17%), Hodgkin's (17%) and mantle cell lymphoma (15%). Two hundred and forty six patients (64%) were transplanted after 2nd line chemotherapy and the median number of prior lines of chemotherapy of 2 (1-9). Two hundred and sixty patients (67%) had received prior platinum chemotherapy and only 4% had a history of prior chronic renal failure (Table 1). The median creatinine level at conditioning initiation was 71(36-206) µmol/l. Be was administered at a median dose of 191 mg/m2/day (50-250) on day -7 and -6. Thirty two percent received 100-160 mg/m²/d and 58% of patients received more than 160 mg/m²/d. Median 24h-hydration volume was 3 l (1-6) which began within median time of 18 h (1-72) prior to conditioning initiation. The median duration time of Be perfusion was 60 min (30-143). Grade 1-4 acute renal failure (ARF) was reported in 107 cases (28%) (G ≥2; 34%) and appeared after a median time of 2 days (1-18) after conditioning start. Melphalan dosage was reduced, due to renal failure, in 10% of patients (Table 2). 84% of patients normalized their creatinine level within a median time of 10 days (1-77). The most frequent reported Grade 1-4 toxicities were mucositis (84%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%) and cardiac rhythm disorders (4%). Opportunistic infection was documented in 9.5% of patients, HHV6 reactivation in 6% of patients. Ten percent of patients needed intensive care management and toxic death was estimated at 5% (Table 3). Patients received a median of 3 (0-34) packed red blood cells and 4 (0-56) platelets units. The median time to neutrophils > 0.5 G/L and platelets > 20 G/L were 10 (0-50) and 12 (0-210) days. The median time of hospital stay was 23 (12-85) days. In comparison with the group of patient without renal failure, the group of patients with ARF had older age (58 vs 54), higher rate of pre-transplant chronic renal failure (10% vs 1%), higher rate of platinum treatment (77% vs 64%), higher day1 creatinine level (81 vs 69) and received higher median bendamustine (199 vs 182). Colitis (p=0.039), pneumonitis (p=0.008), cardia arrhythmia (p=160mg/m2 and age were independent prognostic factors for ARF. A three-point clinical predictor score for acute renal failure was identified and included creatinine level>65µmol/l, bendamustine dose >160mg/m² and age>57 years. ARF stratified by score, was 4% with score 0, 17% with score 1, 30% with score 2 and 45% with score 3. In conclusion, BeEAM induced 5% non-relapse mortality with high rate of renal toxicity. A simple, three-point scoring system can stratify patients by levels of risk for ARF. Rapid identification of higher risk patients may allow a reduction of the bendamustine dose to improve clinical outcomes. Prospective comparative studies are needed to confirm toxicity extents of this conditioning as compared with other type of high dose therapy. Disclosures Soussain: Pharmacyclics: Research Funding; Celgene: Research Funding; Roche: Research Funding. Malak:Novartis: Membership on an entity's Board of Directors or advisory committees.
Published: 2016
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44. Efficacy of the Ribvd Regimen in High Risk Mantle Cell Lymphoma Patients As Defined By the Mipic Prognostic Score: Identification of KI67, LDH and Performance Status As Most Important Prognostic Factors (PF). a French Lysa Group Study

Author: Krimo Bouabdallah, Guillaume Cartron, Christiane Mounier, Jehan Dupuis, Selim Corm, Caroline Dartigeas, Nicolas Daguindau, Roch Houot, Steven Le Gouill, J. Fleury, Fabrice Jardin, Luc Fornecker, Anne Schmitt, Adrien Tempescul, Loic Ysebaert, Barbara Burroni, Anne Moreau, Remy Gressin, Jean-Michel Pignon, Sylvain Carras, and Lionel Karlin
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Proliferation index, Immunology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, Internal medicine, medicine, Univariate analysis, Performance status, business.industry, Cell Biology, Hematology, medicine.disease, Surgery, Log-rank test, Regimen, 030104 developmental biology, B symptoms, 030220 oncology & carcinogenesis, Mantle cell lymphoma, medicine.symptom, business
Abstract: Background The proliferation index (PI), defined by KI67 protein expression has been identified as a key prognostic factor (PF) in mantle cell lymphoma (MCL) (1, 2). A GOELAMS/LYSA study (n = 113 patients) identified a cut point of 26% for KI67 positivity as an independent predictor of overall survival together with LDH levels, B symptoms and ECOG-PS, in MCL (GOELAMS index : GI). (1) Recently, the European MCL network confirmed the independent prognostic power of KI67 protein expression levels to predict OS in MCL (n = 508) and proposed a new score "MIPIc" (KI67cut-off of 30%). (2) While these scores show prognostic impact in the immuno-chemotherapy setting, with or without ASCT and / or maintenance therapy, their predictive power in the setting of targeted therapy remains uncertain. Objective The aim of this study was to test the predictive power of the MIPIc and GI prognostic indices in a cohort of elderly MCL patients treated by a proteasome-inhibitor-based immunochermotherapy regimen within a prospective phase II trial of the LYSA group (LyMa SA 2010 ; Rituximab, Bendamustine, Velcade and Dexamethasone regimen : RiBVD). (3) Material and method The final analysis of the LyMA SA 2010, presented at ASH 2014 (3), showed overall clinical and molecular response rates of 86.5% and 85%. The 24 months estimated OS and PFS was respectively 80% and 70%. (3) In order to assess the prognostic power of KI67 expression levels for OS, all survival data were updated. KI67 staining was performed and reviewed centrally by one pathologist of the LYSA-P, according to the European guidelines. (4) The MIPIc and GI scores were calculated and their impact on survival analyzed (Logrank). In addition, all 6 variables comprising the MIPc and the GI indices were assessed separately by univariate analyzes for prognostic value (these were LDH, ECOG and KI67 that are common to the 2 indices, and Age and WBC for the MIPIc and B Symptoms for GI). Finally a Logrank permitted to define 3 groups of patients with a high statistically impact on survivals with the 3 common variables of MIPIc and GI. Results Among the 74 elderly MCL patients treated in first line by the RiBVD regimen, 59 are alive with a median follow up of 40 months. Estimated OS and PFS at 36 months are respectively 78.4% and 65%. The MIB1 was evaluated on 58 samples for which the MIPIc and GI could be calculated for 57 patients (no LDH value for one patient). MIPIc and GI were not able to define relevant prognostic subgroups for OS (p =0.55 and 0.11). Only the 3 common variables LDH (N vs >N), ECOG (O-1 vs >1) and MIB1 (with a cut-off at 46% corresponding to the fourth quartile of MIB1 expression levels) were individually predictive of OS by univariate analysis (respectively with p=0.0006, p=0.048 and p=0.0031). With these three variables the Logrank test separated three groups that were statistically discriminant for OS and PFS: one group with 0 risk factors n=24 patients, 42%), a second group with one risk factor (n=20 patients, 32%) and the last group with 2 or 3 risk factors (n=13 patients, 23%). Hence the 3 year OS of these 3 groups was respectively 96%, 75% and 30% (p In Conclusion The proteasome-inhibitor-based immunochemotherapy regimen, RiBVD, induces prolonged survival of "High risk" patients, as defined by this modified MIPIc score. More proliferative disease, defined by a KI67 superior to 46%, combined with a high LDH level and/or a high PS defines a high subgroup of patients under the RiBVD regimen (median PFS and OS of respectively 15 and 10 months). Ref: 1 Gressin R, Haematologica 2010. 2 Hoster E et al, J Clin Oncol 2016. 3 Gressin R et al, ASH Blood 2014. 4 Klapper W, H Hematop 2009. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Cartron: Roche: Consultancy, Honoraria; Celgene: Honoraria; Gilead: Honoraria; Jansen: Honoraria. Dartigeas:Roche: Consultancy; Mundipharma: Other: travel grant. Dupuis:janssen: Honoraria; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Karlin:takeda: Consultancy; Bristol: Consultancy; celgene: Consultancy, Honoraria; janssen-cilag: Consultancy, Honoraria; amgen: Consultancy, Honoraria.
Published: 2016
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45. Management of Post-Transplant Lymphoproliferative Disorders in the Real Life: The French Attitude Between 2010 and 2013

Author: Noel Milpied, Julien Rossignol, Gandhi Damaj, Sarah Guenounou, Eric Durot, Norbert Ifrah, Caroline Algrin, Antoine Bonnet, Jérôme Cornillon, Veronique Leblond, Emmanuel Gyan, Sylvain Choquet, Inès Boussen, Adrien Chauchet, Adrien Tempescul, Jeremy Delage, Arnaud Jaccard, and Fontanet Bijou
Subjects: medicine.medical_specialty, Pediatrics, business.industry, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Organ transplantation, Transplantation, hemic and lymphatic diseases, Multicenter trial, Epidemiology, medicine, Rituximab, business, Diffuse large B-cell lymphoma, Kidney transplantation, medicine.drug, Cohort study
Abstract: Introduction Post-transplant lymphoproliferative disorders (PTLD) are a rare but severe complication occurring after organ transplantation as a result of immunosuppressive therapy (IST). Until recently, there was no consensus regarding best treatment practice. In 2006, a phase 2 trial using a monotherapy with rituximab showed an overall response rate of 44%, with a complete response (CR) rate of 28%. In 2012, the PTLD-1 international multicenter trial evaluating rituximab followed by CHOP chemotherapy proved an efficacy of 90% and an overall survival of 6.6 years in PTLD treatment. K-virogref is a French national expert network created in 2011 to structure and improve the management of viro-induced cancers, occurring in adult after transplantation, including PTLD. Within this network, an epidemiological observational study has been set up in September 2013. The aim of our study was to analyze the management of PTLD in France before the creation of the national database of K-virogref. Patients and methods We included solid organ or allogeneic stem cell recipients, aged 18 years and above, with a histologically proven PTLD, diagnosed between January 2010 and September 2013 in 19 French hematology departments. We collected from clinical charts data regarding transplant characteristics, PTLD presentation, first-line treatment and outcomes. Results The study population consisted of 94 patients, 67% were men and median age was 53 years (ranging 18 - 81 years). The majority of patients received kidney transplantation (54%), followed in almost equal proportion by heart (13%), liver (13%) and allogeneic stem cell transplantation (10%). Most of the time (80% of patients), PTLD occurred more than one year after organ transplantation with a median delay of 7.8 years. Histologically, mainly monomorphic PTLD were observed with 66% of diffuse large B cell lymphoma and PTLD was EBV associated in 54%. At the time of diagnosis, 80% were classified as stage IV according to Ann Arbor. The median follow-up time was 28.3 months (ranging 0.2 - 78 months). As far as treatment is concerned, modification of IST was performed in 68% of patients but response was rarely evaluable because a specific treatment was often started at the same time. Surprisingly, first line treatment consisted in rituximab alone or rituximab followed by CHOP chemotherapy in only 32% of the patients. Among these patients, the overall response rate was 81% with 55% of CR. Most patients (56%) received chemotherapy (n=11) or immunochemotherapy (n=46) without previous rituximab therapy. For these patients the overall response rate was 71% with a CR rate of 53%. At 1 and 3 years of follow-up, the relapse-free rates were 56% (95% confidence interval (CI) 46% - 68%) and 47% (95% CI 37% - 60%), respectively. Overall, 49% of patients died during follow-up of which 37% due to infectious complications and 32% due to PTLD progression. Conclusion This is one of the largest cohort study of PTLD in the literature, providing an overview of epidemiological features, treatments and outcomes of this rare disease. The lag between the management of PTLD and literature data emphasizes the usefulness of a national expert network such as K-virogref in order to generalize a less toxic and more powerful attitude. Disclosures Leblond: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Choquet:Celgene: Consultancy; Janssen: Consultancy.
Published: 2016
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46. Identification of patients with indolent B cell lymphoma sensitive to rituximab monotherapy

Author: Christophe Jamin, Pierre Youinou, Solène Querellou, Christian Berthou, Pascal Hutin, Yves Renaudineau, Boutahar Bendaoud, Jacques-Olivier Pers, Divi Cornec, Adrian Tempescul, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Department of Nuclear Medicine, and Laboratoire d'Immunologie et Immunothérapie
Subjects: Oncology, Male, MESH: Tumor Burden, MESH: Complement C1q, MESH: Neoplasm Grading, Multimodal Imaging, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, hemic and lymphatic diseases, B-Cell Activating Factor, Norleucine, Medicine, B-cell lymphoma, MESH: Treatment Outcome, MESH: Aged, Hematology, MESH: Middle Aged, biology, General Medicine, Middle Aged, Prognosis, 3. Good health, Tumor Burden, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Female, Antibody, medicine.drug, Adult, medicine.medical_specialty, Lymphoma, B-Cell, Antineoplastic Agents, MESH: Positron-Emission Tomography and Computed Tomography, MESH: Receptors, IgG, MESH: Prognosis, 03 medical and health sciences, Pharmacokinetics, Internal medicine, MESH: Polymorphism, Genetic, Humans, MESH: Norleucine, MESH: B-Cell Activating Factor, B-cell activating factor, Aged, MESH: Lymphoma, B-Cell, Polymorphism, Genetic, MESH: Humans, business.industry, Complement C1q, Receptors, IgG, MESH: Adult, medicine.disease, MESH: Male, Lymphoma, Non-Hodgkin's lymphoma, MESH: Antibodies, Monoclonal, Murine-Derived, Positron-Emission Tomography, Immunology, biology.protein, MESH: Antineoplastic Agents, Neoplasm Grading, business, Tomography, X-Ray Computed, MESH: Female, 030215 immunology
Abstract: International audience; The potential predictive value of tumor bulk, genetic, and immunological variants in patients with low-grade non-Hodgkin's lymphoma to respond to treatment with rituximab (RTX) monotherapy was evaluated. Thus, the value of assessing the effect of 18-fluoro-desoxy-D-glucose (FDG) uptake on PET scan, polymorphisms in Fc gamma receptor (FcγR) IIIa-158, FcγRIIa-131, and C1qA-276 genes in predicting the response to treatment were evaluated in 50 low-grade non-Hodgkin's lymphoma patients. The influence of RTX pharmacokinetics, plasma levels of the B cell-activating factor (BAFF), and human antichimeric antibodies was also investigated. The therapeutic response was evaluated 10 weeks after treatment using revised Cheson's criteria. Lower maximal standardized uptake values (SUV(max)) at baseline were predictive of complete response. FcγRIIIa-158 polymorphism was also associated with complete response to RTX confirming previous findings, whereas polymorphisms in the FcγRIIa-131 and C1qA-276 genes were not. Lower blood levels of RTX were observed in males, but the effectiveness of RTX in males and females was the same. BAFF was not detectable in plasma before or after treatment, and no patients developed human antichimeric antibodies. Low-grade non-Hodgkin's lymphoma patients with a low SUV(max) at baseline and an FcγRIIIa-158 V/V genotype generally had a complete response to RTX.
Published: 2012
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47. ESHAP chemotherapy regimen associated to lenalidomide induces complete isotopic remission in Hodgkin's lymphoma relapsing after autologous stem cell transplantation

Author: Christian Berthou, Gaelle Guillerm, Jean-Christophe Ianotto, Jean-Richard Eveillard, Adrian Tempescul, Michel, Geneviève, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Université européenne de Bretagne - European University of Brittany (UEB)
Subjects: Oncology, MESH: Remission Induction, medicine.medical_treatment, Hematopoietic stem cell transplantation, 0302 clinical medicine, Autologous stem-cell transplantation, Recurrence, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, MESH: Cytarabine, Lenalidomide, Etoposide, MESH: Etoposide, Remission Induction, MESH: Thalidomide, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, General Medicine, Chemotherapy regimen, Hodgkin Disease, MESH: Transplantation, Autologous, MESH: Hodgkin Disease, 3. Good health, Thalidomide, MESH: Antineoplastic Combined Chemotherapy Protocols, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Transplantation, Autologous, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: Hematopoietic Stem Cell Transplantation, MESH: Humans, business.industry, MESH: Adult, Hodgkin's lymphoma, medicine.disease, MESH: Recurrence, MESH: Cisplatin, Immunology, Prednisone, Cisplatin, business, ESHAP, MESH: Prednisone, 030215 immunology
Abstract: International audience; One way for intravenous Ig (IVIg) to affect responses of the B cells might be to operate through their TLR7 and TLR9. We confirm the ability of TLR agonists to induce CD25 expression in B cells. For this to occur, sialylated Fc-gamma of IgG included in the IVIg preparation are required. As a result, IVIg suppresses TLR-induced production of the proinflammatory IL-6, but not that of the anti-inflammatory IL-10. That is, IVIg mimics the effects of the MyD88 inhibitor. Finally, as we previously showed that IVIg induces CD22 to recruit the inhibitory SHP-1, we established that this enzyme was also involved in IVIg-induced inhibition of TLR9 signaling. This is the first report to demonstrate such a mechanism underlying the negative impact of IVIg on B lymphocytes.
Published: 2011

48. Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease

Author: R. Le Calloc’h, Jean-Christophe Ianotto, Adrian Tempescul, and Christian Berthou
Subjects: Chemotherapy, business.industry, lcsh:RC633-647.5, medicine.medical_treatment, viruses, virus diseases, Case Report, Immunosuppression, General Medicine, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, medicine.disease_cause, Asymptomatic, Nephropathy, Lymphoma, BK virus, Transplantation, Immunology, medicine, medicine.symptom, business, Hemorrhagic cystitis
Abstract: Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.
Published: 2011

49. Combined therapy associating systemic platinum-based chemotherapy and local radiotherapy into the treatment of primary intraocular lymphoma

Author: Christian Berthou, Jean-Christophe Ianotto, Catherine Marianowski-Cochard, Adrian Tempescul, Olivier Pradier, Michel, Geneviève, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service Hématologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Department of Ophthalmology, University Hospital Brest, and Université européenne de Bretagne - European University of Brittany (UEB)
Subjects: Oncology, medicine.medical_specialty, MESH: Combined Modality Therapy, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, MESH: Eye Neoplasms, 03 medical and health sciences, 0302 clinical medicine, MESH: Aged, 80 and over, Internal medicine, Medicine, Combined Modality Therapy, ComputingMilieux_MISCELLANEOUS, MESH: Aged, Chemotherapy, Hematology, MESH: Humans, business.industry, General Medicine, medicine.disease, MESH: Injections, Intravenous, 3. Good health, Radiation therapy, MESH: Antineoplastic Combined Chemotherapy Protocols, Local radiotherapy, 030220 oncology & carcinogenesis, MESH: Radiotherapy, Conformal, 030221 ophthalmology & optometry, Combined therapy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Intraocular lymphoma, MESH: Platinum Compounds, business, MESH: Lymphoma
Abstract: International audience
Published: 2011

50. 18F-FDG PET/CT in primary non-Hodgkin's lymphoma of the sinonasal tract

Author: Sylvie Boisramé, Christian Berthou, Gerald Valette, Solène Querellou, Adrian Tempescul, Jean-Christophe Ianotto, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Department of Nuclear Medicine, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of Odontology, Department of ORL, Université européenne de Bretagne - European University of Brittany (UEB), and Michel, Geneviève
Subjects: medicine.medical_specialty, Pathology, MESH: Remission Induction, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Tomography, Emission-Computed, MESH: Vincristine, MESH: Prognosis, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, MESH: Doxorubicin, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin, MESH: Fluorodeoxyglucose F18, Internal medicine, medicine, MESH: Cytarabine, ComputingMilieux_MISCELLANEOUS, MESH: Aged, MESH: Paranasal Sinus Neoplasms, Hematology, MESH: Humans, MESH: Middle Aged, business.industry, MESH: Organoplatinum Compounds, MESH: Cyclophosphamide, General Medicine, Sinonasal Tract, medicine.disease, MESH: Positron-Emission Tomography, Non-Hodgkin's lymphoma, MESH: Antineoplastic Combined Chemotherapy Protocols, 030220 oncology & carcinogenesis, MESH: Dexamethasone, [SDV.IMM]Life Sciences [q-bio]/Immunology, Fdg pet ct, Radiology, business, MESH: Paranasal Sinuses, MESH: Prednisone
Abstract: International audience
Published: 2010

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