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4 results on '"MESH : Purines"'

1. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study

Author

STEPHANE NANCEY, Francois MION, Nathalie Ganne-Carrié, Dany GARGOT, ANTOINE CORTOT, Laurent Siproudhis, Bernard FLOURIE, ROBERT BENAMOUZIG, Tabassome SIMON, Frederic Gottrand, Guillaume Savoye, Gerard Thiefin, Fabrice Carrat, Jean-Pierre Hugot, Pierre DESREUMAUX, Laurent Peyrin-biroulet, Laurent Michaud, Christos CHRISTIDIS, Olivier Hermine, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service d'Anatomie et Cytologie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hopital Necker-Enfants Malades, Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Hépato-gastroentérologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Infection bactérienne, inflammation, et carcinogenèse digestive, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -IFR50-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunité muqueuse et vaccination, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR50-Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Registre des hémopathies malignes de Côte d'Or, Service d'hématologie biologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Agents pathogènes et inflammation - UFC (EA 4266) ( API ), Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Lipides - Nutrition - Cancer (U866) (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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Male, Time Factors, MESH : Age Distribution, MESH : Prospective Studies, MESH : Aged, Inflammatory bowel disease, MESH: Proportional Hazards Models, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, Crohn Disease, Risk Factors, MESH: Risk Factors, MESH : Purines, MESH : Female, Prospective Studies, MESH: Incidence, Prospective cohort study, MESH : Immunosuppressive Agents, MESH : Sex Distribution, MESH: Aged, MESH : Tumor Necrosis Factor-alpha, Crohn's disease, MESH: Middle Aged, Thiopurine methyltransferase, biology, MESH : Lymphoproliferative Disorders, Incidence, MESH: Sex Distribution, General Medicine, MESH: Purines, Middle Aged, MESH : Adult, MESH : Colitis, Ulcerative, Ulcerative colitis, MESH : Risk Factors, MESH : Incidence, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, MESH: Immunosuppressive Agents, Immunosuppressive Agents, Cohort study, MESH : Time Factors, Adult, medicine.medical_specialty, MESH : Male, MESH: Colitis, Ulcerative, Lymphoproliferative disorders, MESH : Crohn Disease, MESH: Multivariate Analysis, 03 medical and health sciences, Age Distribution, Internal medicine, medicine, Humans, MESH : Middle Aged, Sex Distribution, MESH : France, MESH: Age Distribution, Aged, Proportional Hazards Models, MESH: Humans, MESH: Crohn Disease, Tumor Necrosis Factor-alpha, business.industry, MESH : Drug Therapy, Combination, MESH: Time Factors, MESH : Humans, MESH : Multivariate Analysis, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, MESH : Proportional Hazards Models, Lymphoproliferative Disorders, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, MESH: Drug Therapy, Combination, Purines, MESH: Tumor Necrosis Factor-alpha, Multivariate Analysis, biology.protein, Colitis, Ulcerative, business, MESH: Female
Abstract

International audience; BACKGROUND: Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS: 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29-40). FINDINGS: At baseline, 5867 (30.1%) of patients were receiving, 2809 (14.4%) had discontinued, and 10,810 (55.5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0.90 per 1000 (95% CI 0.50-1.49) patient-years in those receiving, 0.20/1000 (0.02-0.72) patient-years in those who had discontinued, and 0.26/1000 (0.10-0.57) patient-years in those who had never received thiopurines (p=0.0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 (2.01-13.9, p=0.0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. INTERPRETATION: Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. FUNDING: Programme Hospitalier de Recherche Clinique National (AOM05157), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie.

Published
2009

2. Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model

Author

Laurent Meijer, Gordon B. Mills, Khandan Keyomarsi, Donald H. Lambert, Laura A. Lambert, Na Qiao, Kelly K. Hunt, Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Program in integrative biology. Research Institute, The Hospital for sick children [Toronto] (SickKids), Unité de Chimie Pharmaceutique et Radiopharmacie (UCL-CMFA 7340), Université Catholique de Louvain = Catholic University of Louvain (UCL), School of Environmental Sciences [Norwich], University of East Anglia [Norwich] (UEA), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), The Hospital for Sick Children, Unité de Chimie Pharmaceutique et Radiopharmacie ( UCL-CMFA 7340 ), Université Catholique de Louvain ( UCL ), University of East Anglia [Norwich] ( UEA ), Molécules et cibles thérapeutiques ( MCT ), and Centre National de la Recherche Scientifique ( CNRS )

Subjects
Cancer Research, Cell cycle checkpoint, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, Apoptosis, MESH : Models, Biological, Pharmacology, MESH: Drug Synergism, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Cytotoxins, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, MESH : G2 Phase, MESH : Purines, Cytotoxicity, Tumor Stem Cell Assay, 0303 health sciences, Cytotoxins, MESH: Tumor Stem Cell Assay, Drug Synergism, Sarcoma, MESH: Purines, Cell cycle, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, 030220 oncology & carcinogenesis, MESH: Cytotoxins, medicine.drug, G2 Phase, MESH : Drug Synergism, MESH : Tumor Stem Cell Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Sarcoma, Models, Biological, Article, 03 medical and health sciences, MESH: Doxorubicin, Therapeutic index, medicine, Autophagy, Roscovitine, MESH : Doxorubicin, MESH: Autophagy, Humans, Doxorubicin, MESH: Tumor Cells, Cultured, 030304 developmental biology, Chemotherapy, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Apoptosis, MESH : Humans, MESH: Models, Biological, MESH : Autophagy, MESH: G2 Phase, Purines, MESH: Sarcoma, MESH : Apoptosis
Abstract

Doxorubicin is a genotoxic chemotherapy agent used in treatment of a wide variety of cancers. Significant clinical side effects, including cardiac toxicity and myelosuppression, severely limit the therapeutic index of this commonly used agent and methods which improve doxorubicin efficacy could benefit many patients. Because doxorubicin cytotoxicity is cell cycle specific, the cell cycle is a rational target to enhance its efficacy. We examined the direct, cyclin-dependent kinase inhibitor roscovitine as a means of enhancing doxorubicin cytotoxicity. This study showed synergistic cytotoxicity between doxorubicin and roscovitine in three sarcoma cell lines: SW-982 (synovial sarcoma), U2OS-LC3-GFP (osteosarcoma), and SK-LMS-1 (uterine leiomyosarcoma), but not the fibroblast cell line WI38. The combined treatment of doxorubicin and roscovitine was associated with a prolonged G2-M cell cycle arrest in the three sarcoma cell lines. Using three different methods for detecting apoptosis, our results revealed that apoptotic cell death did not account for the synergistic cytotoxicity between doxorubicin and roscovitine. However, morphologic changes observed by light microscopy and increased cytoplasmic LC3-GFP puncta in U20S-LC3-GFP cells after the combined treatment suggested the induction of autophagy. Induction of autophagy was also shown in SW-982 and SK-LMS-1 cells treated with both doxorubicin and roscovitine by acridine orange staining. These results suggest a novel role of autophagy in the enhanced cytotoxicity by cell cycle inhibition after genotoxic injury in tumor cells. Further investigation of this enhanced cytotoxicity as a treatment strategy for sarcomas is warranted. [Cancer Res 2008;68(19):7966–74]

Published
2008

3. Selective chemical inhibition as a tool to study Cdk1 and Cdk2 functions in the cell cycle

Author

Daniel Fisher, Liliana Krasinska, Emilie Cot, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Phosphorylation and control of the vertebrate cell cycle, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM), Fisher, Daniel, and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Xenopus, MESH: Cell Cycle, MESH: DNA Replication, chemical inhibitors, 0302 clinical medicine, MESH: Ovum, MESH : Thiazoles, Nu6102, MESH : Ovum, MESH: Protein Kinase Inhibitors, MESH: Animals, MESH: Xenopus, MESH : Purines, Cells, Cultured, 0303 health sciences, biology, Kinase, Cell Cycle, MESH : Cyclin-Dependent Kinase 2, MESH: Purines, Cell cycle, MESH: CDC2 Protein Kinase, Chromatin, Cell biology, 030220 oncology & carcinogenesis, Cyclin dependent kinase, Quinolines, biological phenomena, cell phenomena, and immunity, MESH: Quinolines, MESH: Cells, Cultured, MESH : DNA Replication, DNA Replication, MESH: Cyclin-Dependent Kinase 2, MESH : CDC2 Protein Kinase, MESH : Quinolines, MESH: Thiazoles, Article, 03 medical and health sciences, Cyclin-dependent kinase, fibroblasts, CDC2 Protein Kinase, MESH : Cell Cycle, MESH : Cells, Cultured, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein Kinase Inhibitors, Molecular Biology, Mitosis, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene knockout, Ovum, 030304 developmental biology, Cyclin-dependent kinase 1, MESH: Humans, Cyclin-Dependent Kinase 2, MESH : Humans, MESH : Xenopus, Cell Biology, biology.organism_classification, MESH : Protein Kinase Inhibitors, Thiazoles, Purines, biology.protein, chromatin, MESH : Animals, Developmental Biology, RO-3306
Abstract

International audience; Cyclin-dependent kinases are highly conserved among all eukaryotes, and have essential roles in the cell cycle. However, these roles are still only poorly understood at a molecular level, partly due to the functional redundancy of different Cdk complexes. Indeed, mice knockouts have even thrown into some doubt the assumed essential roles for Cdk2-cyclin E in triggering S-phase, but this is almost certainly due to compensation by Cdk1 complexes. By combining both knockout approaches and chemical Cdk inhibition in Xenopus egg extracts, we have shown that one reason for functional redundancy of Cdk control of S-phase is that Cdk activity required to trigger S-phase is very low. Cdk1 contributes to this activity even in the presence of Cdk2, and Cdk activity at this stage does not show "switch-like" regulation, as at the onset of mitosis. It is important to try to confirm and extend these findings to other cell-types, and to explain why different cells might have evolved different requirements for Cdk activity. In this paper, we present data that suggest that selective chemical Cdk inhibition will be a useful tool towards achieving this goal.

Published
2008

4. The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients

Author

Richard Delarue, Mathilde Hunault-Berger, Olivier Tournilhac, Arnaud Jaccard, Philippe Rodon, Pierre Morel, Marc Bernard, Arnaud Hot, Mohamed Hamidou, Benjamin Terrier, Fadi Fakhouri, Olivier Gisserot, Jean-Paul Fermand, Bernard Grosbois, Caroline Elie, Jacques Dantal, Véronique Leblond, Valérie Coiteux, Jean-Luc Harousseau, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation et de recherche en transplantation (ITERT), Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Laboratoire de physique des milieux ionisés et applications (LPMIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de médecine interne, Physique des milieux ionisés et applications (LPMIA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ITUN, Institut de transplantation et de recherche en transplantation ( ITERT ), Laboratoire Hubert Curien [Saint Etienne] ( LHC ), Institut d'Optique Graduate School ( IOGS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des milieux ionisés et applications ( LPMIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP)

Subjects
Male, Pathology, MESH: Remission Induction, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, MESH : Alkylating Agents, MESH: Antigens, CD20, Hematopoietic stem cell transplantation, Gastroenterology, MESH: Antibodies, Monoclonal, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Treatment Outcome, Aged, 80 and over, MESH: Middle Aged, MESH: Heart Diseases, Amyloidosis, MESH: Immunologic Factors, Remission Induction, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, General Medicine, MESH: Immunoglobulin M, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, MESH : Paraproteinemias, Rituximab, medicine.medical_specialty, Alkylating Agents, MESH: Serum Albumin, 03 medical and health sciences, MESH: Lymphatic Diseases, MESH : Antigens, CD20, MESH : Hematopoietic Stem Cell Transplantation, AL amyloidosis, Humans, Immunologic Factors, MESH : Middle Aged, MESH : Aged, 80 and over, Lymphatic Diseases, Aged, Retrospective Studies, MESH: Humans, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Amyloidosis, Complication, MESH: Female, Lung Diseases, Paraproteinemias, Antibodies, Monoclonal, Murine-Derived, MESH: Lung Diseases, MESH: Paraproteinemias, MESH: Aged, 80 and over, MESH : Purines, MESH : Female, Prospective cohort study, MESH: Aged, MESH : Lung Diseases, MESH : Lymphatic Diseases, MESH: Purines, Middle Aged, MESH : Adult, MESH : Survival Rate, Hematologic Response, MESH: Alkylating Agents, Treatment Outcome, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, medicine.drug, Adult, Heart Diseases, MESH: Survival Rate, MESH : Immunoglobulin M, MESH : Male, MESH : Treatment Outcome, MESH : Immunologic Factors, MESH : Serum Albumin, Internal medicine, medicine, MESH: Amyloidosis, MESH : France, Serum Albumin, MESH: Hematopoietic Stem Cell Transplantation, MESH : Remission Induction, business.industry, Retrospective cohort study, MESH : Heart Diseases, Antigens, CD20, MESH: Male, MESH: France, Immunoglobulin M, Purines, business, 030215 immunology
Abstract

International audience; Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known complication of monoclonal IgM-associated disorders. We sought to determine the clinical and laboratory presentation, response to treatment, and outcome of patients with IgM-related amyloidosis in the era of new therapeutic approaches. We conducted a retrospective study in 29 French centers to identify patients with monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and collected relevant clinical and laboratory data. We identified 72 patients with IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64, peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A peculiar pattern of relatively frequent lymph node (31%) and lung (17%) involvement was noted in patients with systemic AL amyloidosis. Response to alkylating agents was poor, with a hematologic response in 37%, a complete remission in 0%, and an organ response in 21%. Response to hematopoietic stem cell transplantation showed a hematologic response in 100% with complete remission in 75% and an organ response in 75%. Purine analogs and rituximab induced a hematologic response in 73% and 60%, respectively, with complete remission in 9% and 0% and an organ response in 55% and 0%, respectively. In multivariate analysis, prognostic factors for survival were serum albumin level < or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective studies are needed in patients with IgM-related amyloidosis, with special emphasis on treatment options: hematopoietic stem cell transplantation and purine analogs could represent the most effective therapies. The identification of adverse prognostic factors of survival could be useful for those managing and making treatment decisions for these patients.

Published
2008

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