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57 results on '"MESH: Transplantation, Homologous"'

1. Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites

Author

Eleonora Latis, David Michonneau, Sivapriya Ramamoorthy, Gérard Socié, Sylvie Chevret, Emmanuel Curis, Régis Peffault de Latour, Brian J. Ingram, Lars Rogge, Laetitia Dubouchet, Flore Sicre de Fontbrune, Marie Robin, Service d'hématologie greffe [Saint-Louis], 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), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunorégulation - Immunoregulation, Institut Pasteur [Paris] (IP), Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Biostatistique, traitement et modélisation des données biologiques (BioSTM - EA 7537), Université Paris Descartes - Paris 5 (UPD5), Metabolon INC, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), DGOS. Alexion Pharmaceutical company (APALEX). Institut National du Cancer (project number INCa 2014-1-PL BIO-07-IP-1). Institut National du Cancer (INCa) and the Agence Nationale de la Recherche (ANR) under the auspices of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)., ANR-13-PRTS-0002,BioGvHD,Biomarqueurs de la maladie du greffon contre l'hôte et de la tolérance immunitaire chez l'homme(2013), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris], Laboratoire de biomathématiques, EA 7537 [Paris] (BioSTM), Université de Paris - UFR Pharmacie [Santé] (UP UFR Pharmacie), Université de Paris (UP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Kop, Marie-Luce, Programme de Recherche Translationnelle en Santé - Biomarqueurs de la maladie du greffon contre l'hôte et de la tolérance immunitaire chez l'homme - - BioGvHD2013 - ANR-13-PRTS-0002 - PRTS - VALID, Université Paris Cité - UFR Pharmacie [Santé] (UPCité UFR Pharmacie), and Université Paris Cité (UPCité)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Male, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Graft vs Host Disease, Hematopoietic stem cell transplantation, Ligands, Cohort Studies, 0302 clinical medicine, Living Donors, MESH: Ligands, Medicine, MESH: Metabolomics, Receptor, lcsh:Science, MESH: Cohort Studies, MESH: Aged, MESH: Living Donors, Multidisciplinary, MESH: Middle Aged, biology, Transplant Immunology, Hematopoietic Stem Cell Transplantation, Tryptophan, Middle Aged, MESH: Case-Control Studies, 3. Good health, [SDV] Life Sciences [q-bio], surgical procedures, operative, MESH: Young Adult, 030220 oncology & carcinogenesis, Acute Disease, Metabolome, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Metabolome, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Plasmalogens, MESH: Graft vs Host Disease, MESH: Bile Acids and Salts, General Biochemistry, Genetics and Molecular Biology, Article, MESH: Gastrointestinal Microbiome, Bile Acids and Salts, 03 medical and health sciences, Young Adult, Immune system, Metabolomics, Translational Research, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Tryptophan, MESH: Hematopoietic Stem Cell Transplantation, Aged, MESH: Humans, business.industry, Siblings, Case-control study, MESH: Adult, General Chemistry, Aryl hydrocarbon receptor, medicine.disease, MESH: Male, Gastrointestinal Microbiome, MESH: Plasmalogens, MESH: Siblings, Transplantation, 030104 developmental biology, Graft-versus-host disease, MESH: T-Lymphocytes, Receptors, Aryl Hydrocarbon, Case-Control Studies, MESH: Receptors, Aryl Hydrocarbon, Immunology, biology.protein, lcsh:Q, business, MESH: Female
Abstract

Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity., Graft versus host disease (GvHD) still hinders allogeneic hematopoietic stem cell transplantation. Here, the authors use metabolomics to analyze two cohorts of paired transplant recipients and donors, identifying significant differences in both host- and microbiota-derived metabolites.

Published
2019
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2. Complement fragments are biomarkers of antibody-mediated endothelial injury

Author

Erik Stites, Moglie Le Quintrec, Jennifer Laskowski, Brian M. Freed, Brandon Renner, Diana Jalal, James E. Cooper, Zhiying You, Joshua M. Thurman, University of Colorado Anschutz [Aurora], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CLINIMMUNE LABS Bioscience, Carver College of Medicine [Iowa City], and University of Iowa [Iowa City]

Subjects
Graft Rejection, Male, 0301 basic medicine, Biopsy, MESH: Allografts, Kidney, Antibody mediated rejection, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Kidney Transplantation, MESH: Biopsy, 0302 clinical medicine, MESH: Endothelial Cells, Complement Activation, Cells, Cultured, MESH: Middle Aged, biology, Microvesicle, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Allografts, 3. Good health, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, MESH: Cells, Cultured, Adult, MESH: Complement Activation, Immunology, MESH: Complement System Proteins, Complement, MESH: Graft Rejection, MESH: Vascular System Injuries, Antibodies, Article, 03 medical and health sciences, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Donor specific antibody, Molecular Biology, Opsonin, MESH: Humans, business.industry, MESH: Antibodies, C4A, Endothelial Cells, MESH: Adult, Complement System Proteins, Biomarker, MESH: Kidney, Vascular System Injuries, Kidney Transplantation, Microvesicles, In vitro, MESH: Male, Complement system, 030104 developmental biology, biology.protein, MESH: Biomarkers, business, MESH: Female, Biomarkers, 030215 immunology
Abstract

International audience; Antibody-mediated rejection (AbMR) adversely affects long-term graft survival in kidney transplantation. Currently, the diagnosis of AbMR requires a kidney biopsy, and detection of complement C4d deposition in the allograft is one of the diagnostic criteria. Complement activation also generates several soluble fragments which could potentially provide non-invasive biomarkers of the process. Furthermore, microvesicles released into the plasma from injured cells can serve as biomarkers of vascular injury. To explore whether soluble complement fragments or complement fragments bound to endothelial microvesicles can be used to non-invasively detect AbMR, we developed an in vitro model in which human endothelial cells were exposed to anti-HLA antibodies and complement sufficient serum. We found that complement fragments C4a and sC5b-9 were increased in the supernatants of cells exposed to complement-sufficient serum compared to cells treated complement-deficient serum. Furthermore, complement activation on the cell surface was associated with the release of microvesicles bearing C4 and C3 fragments. We next measured these analytes in plasma from kidney transplant recipients with biopsy-proven acute AbMR (n = 9) and compared the results with those from transplant recipients who also had impaired allograft function but who did not have AbMR (n = 30). Consistent with the in vitro results, complement fragments C4a and Ba were increased in plasma from patients with AbMR compared to control subjects (P

Published
2020
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3. The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

Author

Antoine Blancher, Takashi Shiina, Tokai University, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Pistre, Karine

Subjects
0301 basic medicine, [SDV.BA] Life Sciences [q-bio]/Animal biology, Review, Genome, Major Histocompatibility Complex, 0302 clinical medicine, MESH: Macaca fascicularis / genetics, Gene Duplication, Gene duplication, MESH: Animals, lcsh:QH301-705.5, [SDV.BA]Life Sciences [q-bio]/Animal biology, MESH: Gene Duplication, General Medicine, Phenotype, experimental medicine, MESH: Models, Animal, Models, Animal, [SDV.IMM]Life Sciences [q-bio]/Immunology, cynomolgus macaque, medicine.medical_specialty, Old World, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Biology, Major histocompatibility complex, MHC polymorphism, 03 medical and health sciences, Immune system, MESH: Major Histocompatibility Complex, Molecular genetics, MHC class I, MESH: Polymorphism, Genetic, medicine, MESH: Transplantation, Homologous, Animals, Transplantation, Homologous, MESH: Genome, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Polymorphism, Genetic, nonhuman primate models, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Macaca fascicularis, 030104 developmental biology, lcsh:Biology (General), Evolutionary biology, biology.protein, 030215 immunology
Abstract

Among the non-human primates used in experimental medicine, cynomolgus macaques (Macaca fascicularis hereafter referred to as Mafa) are increasingly selected for the ease with which they are maintained and bred in captivity. Macaques belong to Old World monkeys and are phylogenetically much closer to humans than rodents, which are still the most frequently used animal model. Our understanding of the Mafa genome has progressed rapidly in recent years and has greatly benefited from the latest technical advances in molecular genetics. Cynomolgus macaques are widespread in Southeast Asia and numerous studies have shown a distinct genetic differentiation of continental and island populations. The major histocompatibility complex of cynomolgus macaque (Mafa MHC) is organized in the same way as that of human, but it differs from the latter by its high degree of classical class I gene duplication. Human polymorphic MHC regions play a pivotal role in allograft transplantation and have been associated with more than 100 diseases and/or phenotypes. The Mafa MHC polymorphism similarly plays a crucial role in experimental allografts of organs and stem cells. Experimental results show that the Mafa MHC class I and II regions influence the ability to mount an immune response against infectious pathogens and vaccines. MHC also affects cynomolgus macaque reproduction and impacts on numerous biological parameters. This review describes the Mafa MHC polymorphism and the methods currently used to characterize it. We discuss some of the major areas of experimental medicine where an effect induced by MHC polymorphism has been demonstrated.

Published
2019
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4. Osmoregulation Performance and Kidney Transplant Outcome

Author

Christophe Legendre, Jordan Jouffroy, Manal Mazloum, Dominique Prié, Dany Anglicheau, Antoine Neuraz, François Brazier, Nicolas Garcelon, Frank Bienaimé, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Néphrologie [CHU Necker], and Neuraz, Antoine

Subjects
medicine.medical_specialty, Urology, Renal function, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Kidney Transplantation, Osmoregulation, Up Front Matters, MESH: Osmoregulation, MESH: Transplantation, Homologous, medicine, MESH: Sodium, Humans, Transplantation, Homologous, Prospective Studies, Risk factor, Prospective cohort study, Kidney transplantation, MESH: Humans, business.industry, Hazard ratio, Sodium, General Medicine, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Transplantation, MESH: Prospective Studies, Confidence interval, Transplantation, MESH: Glomerular Filtration Rate, Nephrology, Hyponatremia, business, Glomerular Filtration Rate
Abstract

International audience; Background Kidney transplant recipients have an impaired ability to dilute urine but seldom develop baseline hyponatremia before ESRD. Although hyponatremia is a risk factor for adverse events in CKD and in kidney transplant recipients, it remains unclear whether subtler alterations in osmoregulation performance are associated with outcome. Methods We studied a single-center prospective cohort of 1258 kidney transplant recipients who underwent a water-loading test 3 months after transplant to determine osmoregulation performance. Measured GFR (mGFR) was performed at the same visit. A group of 164 healthy candidates for kidney donation served as controls. We further evaluated the association of osmoregulation performance with transplantation outcomes and subsequent kidney function. Results Unlike controls, most kidney transplant recipients failed to maintain plasma sodium during water loading (plasma sodium slope of −0.6±0.4 mmol/L per hour in transplant recipients versus −0.12±0.3 mmol/L per hour in controls; P

Published
2018
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5. Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function

Author

Michel Bessodes, Pascal Houzé, Johanne Seguin, Katia Lemdani, Nathalie Mignet, Rabah Gahoual, Daniel Scherman, Hugo Salmon, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Centre de recherche de Vitry-Alfortville, Rhone Poulenc SA, Laboratoire de Neurochimie, Hospices Civils de Lyon (HCL), Mignet, Nathalie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris sciences et lettres (PSL), Service de biochimie métabolique [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), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Paris Sciences et Lettres (PSL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and PSL Research University (PSL)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Contrast Media, Lactose, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SPI.MAT]Engineering Sciences [physics]/Materials, chemistry.chemical_compound, Mice, MESH: Liver Neoplasms, [CHIM] Chemical Sciences, General Materials Science, Tissue Distribution, MESH: Animals, Mice, Inbred BALB C, medicine.diagnostic_test, Liver Neoplasms, Optical Imaging, [CHIM.MATE]Chemical Sciences/Material chemistry, Carbocyanines, Human serum albumin, Fluorescence, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Biochemistry, Liver, Hepatocyte, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Female, MESH: Carbocyanines, medicine.drug, MESH: Cell Line, Tumor, MESH: Mice, Inbred BALB C, MESH: Serum Albumin, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Flow cytometry, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Cell Line, Tumor, MESH: Contrast Media, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, [CHIM]Chemical Sciences, MESH: Lactose, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], MESH: Tissue Distribution, MESH: Mice, Serum Albumin, MESH: Optical Imaging, MESH: Humans, Albumin, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 030104 developmental biology, chemistry, Liver function, MESH: Female, MESH: Liver
Abstract

International audience; In the context of increasing liver diseases, no contrast agent is currently available in Europe and the United States to directly assess the liver function. Only neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of liver functional cells (l-Cyal). Precise characterization was achieved in order to determine the amounts of lactose and Cyanine 5 (Cy5) coupled to the albumin. In addition, potential aggregation was characterized by asymmetrical flow field-flow fractionation hyphenated to multi-angle light scattering (AF4-MALS). The optimal functionalized albumin exhibited a mass greater than 87 kDa which corresponds to the addition of 34 lactose moieties per protein and 1-2 Cy5 labels. Also, no significant formation of aggregates could be identified due to the modification of the native albumin. In healthy mice, the accumulation of l-Cyal in the liver and its selectivity for hepatocyte cells were shown by optical imaging and flow cytometry. Administration of l-Cyal to mice bearing liver metastases showed a reduced signal in the liver related to a decrease in the number of hepatocytes. The l-Cyal bioimaging contrast agent could be particularly useful for assessing the state of liver related diseases.

Published
2018
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6. Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy

Author

Martin Carre, Olivier Epaulard, Jean-Yves Cahn, Patrice Morand, Julien Lupo, Anne Thiebaut, Claude-Eric Bulabois, Touyana Semenova, Raphaële Germi, Chloe Wackenheim, Mihaja Raberahona, Hôpital Joseph Raseta Befelatanana, CHU d’Antananarivo, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Department of infectious diseases, CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Oncology, Male, Epstein-Barr Virus Infections, Herpesvirus 4, Human, medicine.medical_treatment, Hematopoietic stem cell transplantation, medicine.disease_cause, MESH: Virus Activation, 0302 clinical medicine, rituximab, MESH: Lymphoproliferative Disorders, immune system diseases, hemic and lymphatic diseases, preemptive therapy, MESH: Immunocompromised Host, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, MESH: Epstein-Barr Virus Infections, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Immunologic Factors, Middle Aged, 3. Good health, viral load, Infectious Diseases, Treatment Outcome, surgical procedures, operative, MESH: Young Adult, MESH: Survival Analysis, hematopoietic stem cell transplantation, Rituximab, Female, MESH: Rituximab, MESH: Viral Load, Viral load, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Virus, 03 medical and health sciences, Immunocompromised Host, Young Adult, Rituximab therapy, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Immunologic Factors, Transplantation, Homologous, Epstein-Barr virus, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Adolescent, Transplantation, MESH: Humans, business.industry, MESH: Adult, MESH: Herpesvirus 4, Human, MESH: Retrospective Studies, Epstein–Barr virus, Survival Analysis, Lymphoproliferative Disorders, MESH: Male, MESH: DNA, Viral, 030104 developmental biology, Epstein barr, Median time, Immunology, DNA, Viral, Virus Activation, business, MESH: Female, 030215 immunology
Abstract

Background Epstein-Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post-HSCT BEBVL dynamics, and the threshold that should lead to anti-CD20 therapy is poorly defined. Methods We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in our center from 2005 to 2013, including the effect of rituximab. Results Detection of BEBVL > 100, 1000, 5000, 10,000, and 50,000 copies/mL occurred in respectively 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was associated with an overall survival difference. Seventy-eight patients received rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL, long-term survival did not differ in rituximab-treated and non-treated, except for patients with BEBVL ≥50,000. Only 1 case of PTLD was observed. Conclusions BEBVL is frequently detectable after HSCT, but suggests no strong association with survival. Preemptive rituximab therapy threshold remains to be defined. This article is protected by copyright. All rights reserved.

Published
2016
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7. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI

Author

David I. Marks, Richard T. Maziarz, Mehdi Hamadani, Mary M. Horowitz, Vivek Roy, Kwang Woo Ahn, Wael Saber, Alison W. Loren, Rammurti T. Kamble, Eduardo Olavarria, Mark R. Litzow, Joerg Halter, Yoshihiro Inamoto, Jean-Yves Cahn, Gregory A. Hale, Bipin N. Savani, Baldeep Wirk, Jeff Szer, Matthew D. Seftel, Harry C. Schouten, Edmund K. Waller, Mitchell Sabloff, Edward A. Copelan, Luciano J. Costa, Brian J. Bolwell, Daniel J. Weisdorf, Koen van Besien, Mukta Arora, Marcos de Lima, Christopher Bredeson, Mahmoud Aljurf, Robert Peter Gale, Jorge E. Cortes, Betty K. Hamilton, Belinda R. Avalos, Celalettin Ustun, Matt Kalaycio, Xiaochun Zhu, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Vanderbilt University [Nashville], University Hospital Basel [Basel], Mayo Clinic, Genetica & Celbiologie, Interne Geneeskunde, and RS: GROW - School for Oncology and Reproduction

Subjects
Oncology, MESH: Remission Induction, MESH: Combined Modality Therapy, MESH: Busulfan, medicine.medical_treatment, MESH: Leukemia, Myeloid, Plenary Paper, Hematopoietic stem cell transplantation, Biochemistry, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Unrelated Donors, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Child, MESH: Treatment Outcome, MESH: Middle Aged, Myeloid leukemia, Hematology, Total body irradiation, 3. Good health, Leukemia, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Acute Disease, MESH: Whole-Body Irradiation, medicine.drug, medicine.medical_specialty, Cyclophosphamide, Immunology, MESH: Multivariate Analysis, 03 medical and health sciences, Internal medicine, medicine, MESH: Transplantation, Homologous, neoplasms, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Humans, business.industry, MESH: Time Factors, MESH: Child, Preschool, MESH: Cyclophosphamide, MESH: Adult, Cell Biology, medicine.disease, Confidence interval, MESH: Male, nervous system diseases, MESH: Siblings, Transplantation, MESH: Disease-Free Survival, business, MESH: Female, Busulfan, 030215 immunology
Abstract

International audience; Cyclophosphamide combined with total body irradiation (Cy/TBI) or busulfan (BuCy) are the most widely used myeloablative conditioning regimens for allotransplants. Recent data regarding their comparative effectiveness are lacking. We analyzed data from the Center for International Blood and Marrow Transplant Research for 1230 subjects receiving a first hematopoietic cell transplant from a human leukocyte antigen-matched sibling or from an unrelated donor during the years 2000 to 2006 for acute myeloid leukemia (AML) in first complete remission (CR) after conditioning with Cy/TBI or oral or intravenous (IV) BuCy. Multivariate analysis showed significantly less nonrelapse mortality (relative risk [RR] = 0.58; 95% confidence interval [CI]: 0.39-0.86; P = .007), and relapse after, but not before, 1 year posttransplant (RR = 0.23; 95% CI: 0.08-0.65; P = .006), and better leukemia-free survival (RR = 0.70; 95% CI: 0.55-0.88; P = .003) and survival (RR = 0.68; 95% CI: 0.52-0.88; P = .003) in persons receiving IV, but not oral, Bu compared with TBI. In combination with Cy, IV Bu is associated with superior outcomes compared with TBI in patients with AML in first CR.

Published
2013
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8. Uterine allotransplantation in ewes using an aortocava patch

Author

I. Pommepuy, P. Piver, Marie Essig, L. Fourcade, T. Gauthier, Y. Aubard, C. Couquet, F. Bertin, X. Plainard, M.-J. Cornuejols, A. Maubon, Pierre Marquet, F. Saint Marcoux, Service de Gynécologie-Obstétrique [CHU Limoges], CHU Limoges, Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service de chirurgie pédiatrique viscérale, orthopédique et plastique [CHU Limoges], Service de Radiologie et Imagerie Médicale [CHU Limoges], Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie Pathologique [CHU Limoges], Service de Chirurgie urologique et andrologie [CHU Limoges], Research and Analysis Laboratory, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], and Marquet, Pierre

Subjects
Graft Rejection, Time Factors, Vaginoscopy, medicine.medical_treatment, MESH: Cyclosporine, MESH: Magnetic Resonance Imaging, Endometrium, 0302 clinical medicine, Ischemia, Laparotomy, MESH: Animals, Aorta, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Graft Survival, Rehabilitation, Area under the curve, Obstetrics and Gynecology, MESH: Aorta, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Magnetic Resonance Imaging, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Endometrium, Area Under Curve, 030220 oncology & carcinogenesis, Vagina, Cyclosporine, MESH: Uterus, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, MESH: Graft Survival, MESH: Sheep, MESH: Graft Rejection, Anastomosis, Mycophenolic acid, 03 medical and health sciences, Biopsy, MESH: Transplantation, Homologous, medicine, Animals, Humans, Transplantation, Homologous, MESH: Mycophenolic Acid, Sheep, MESH: Humans, business.industry, Uterus, MESH: Time Factors, Mycophenolic Acid, Surgery, Transplantation, Reproductive Medicine, MESH: Vagina, MESH: Area Under Curve, MESH: Ischemia, business, MESH: Female, Allotransplantation
Abstract

International audience; BACKGROUND: We investigated a novel allotransplantation model using an aortocava patch in ewes. METHODS AND RESULTS: We carried out 10 uterine orthotopic allotransplantations in ewes with end-to-side anastomosis of the aortocava donor patch on the left external iliac vessel recipient. The immunosuppressive protocol was a combination of cyclosporine (10 mg/kg/day) and mycophenolic acid (3 g/day). An estimation of the immunosuppressive therapy exposure was performed by measuring the area under the curve (AUC) of immunosuppressive plasma concentrations. The graft was assessed by vaginoscopy, magnetic resonance imaging (MRI) and second look laparotomy at 6, 8 and 10 weeks, respectively. The median (range) times for cold and warm ischemia were 95 min (75-130) and 91 min (55-165), respectively. All the vascular anastomoses were patent at the end of the surgery. The median AUC of cyclosporine and mycophenolic acid were 1.24 mg h/l (0.34-3.85) and 18.40 mg h/l (3.76-42.35), respectively. Of the 10 ewes receiving a transplant, 6 could be assessed. Cervical biopsies showed signs of necrosis in all six ewes. The MRI results correlated with the macroscopic observations of the 'second look' laparotomy. The aortocava vascular pedicles were thrombosed, adding to the peripheral neovascularization. Graft histology showed endometrial tissue in two out of six ewes. CONCLUSIONS: Mobility of the transplant within the pelvis, the length of the vascular pedicle and rejection can explain the high rate of transplant necrosis. The particular digestive anatomy and physiology of ruminants makes it difficult to administer an optimal immunosuppressive treatment. MRI appears to be a good non-invasive examination for graft estimation.

Published
2011
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9. Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire

Author

Colette Raffoux, Mohamad Mohty, R. Tabrizi, J.Y. Cahn, Ibrahim Yakoub-Agha, J. H. Bourhis, Yosr Hicheri, Norbert Ifrah, Mauricette Michallet, Agnès Buzyn, Nathalie Dhedin, Myriam Labopin, Marie-Lorraine Balere, Didier Blaise, Gérard Socié, Helene Esperou, Noel Milpied, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Bordeaux Segalen - Bordeaux 2, Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre Léon Bérard [Lyon], 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), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut Gustave Roussy (IGR), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), 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), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut Gustave Roussy ( IGR ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Male, MESH: Tissue Donors, Cancer Research, MESH : Retrospective Studies, MESH : Aged, MESH: Rabbits, Graft vs Host Disease, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : HLA Antigens, MESH: Antilymphocyte Serum, HLA Antigens, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Female, MESH: Animals, Cumulative incidence, MESH: Incidence, MESH: HLA Antigens, MESH : Tissue Donors, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Hematology, Histocompatibility Testing, Incidence, Incidence (epidemiology), MESH : Graft vs Host Disease, MESH : Histocompatibility Testing, MESH : Adult, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Incidence, Tissue Donors, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, surgical procedures, operative, Oncology, 030220 oncology & carcinogenesis, Female, Rabbits, MESH: Stem Cell Transplantation, MESH: Leukemia, Myeloid, Acute, MESH: Myelodysplastic Syndromes, Adult, endocrine system, medicine.medical_specialty, Adolescent, MESH : Transplantation, Homologous, MESH : Male, MESH : Leukemia, Myeloid, Acute, MESH : Antilymphocyte Serum, MESH: Graft vs Host Disease, MESH : Myelodysplastic Syndromes, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, MESH: Histocompatibility Testing, MESH : Stem Cell Transplantation, 03 medical and health sciences, MESH : Adolescent, Internal medicine, MESH: Transplantation, Homologous, medicine, Animals, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH : Rabbits, Aged, Antilymphocyte Serum, Retrospective Studies, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, business.industry, Myelodysplastic syndromes, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, Histocompatibility, Transplantation, Graft-versus-host disease, Myelodysplastic Syndromes, Immunology, MESH : Animals, business, MESH: Female, Stem Cell Transplantation, 030215 immunology
Abstract

International audience; This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.

Published
2010
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10. Significance of Serum Bile Acids in Small Bowel Allograft Rejection in Pigs

Author

Thierry Yandza, Jean Gugenheim, Marie-Christine Saint-Paul, Xavier Hébuterne, Veronique M. Braud, Marie F Gerhardt, Service de Chirurgie Digestive et Transplantation Hépatique, Hôpital Archet II, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie, Groupe Hospitalier Paris Saint-Joseph, Service d'Anatomo-Pathologie, Centre Hospitalier Universitaire de Nice (CHU Nice), and Service de Gastroentérologie (Pôle Digestif)

Subjects
Graft Rejection, medicine.medical_specialty, MESH: Intestine, Small, Swine, medicine.drug_class, medicine.medical_treatment, MESH: Graft Rejection, MESH: Bile Acids and Salts, Biology, Rejection, Gastroenterology, Bile Acids and Salts, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Intestine, Small, MESH: Transplantation, Homologous, medicine, Animals, Transplantation, Homologous, MESH: Animals, MESH: Swine, Pig, Transplantation, Bile acid, Pig model, Histology, Serum samples, Bile acids, Intestine, 3. Good health, Intestinal histology, Allograft rejection, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, MESH: Female, Allotransplantation
Abstract

International audience; OBJECTIVES: To examine changes in individual bile acids in serum in a pig model of allogenic small bowel transplantation. METHODS: Seventeen pigs were divided into two groups: group 1 (n=10), controls; group 2 (n=7), allotransplantation, nonimmunosuppressed recipients. Both groups received a segmental intestine. Intestinal specimens for histologic studies were obtained at the end of cold flushing (T0) and on postoperative day 8 (T1). Total and individual bile acid concentrations were measured in serum samples taken at T0 and T1. RESULTS: All animals survived until the end of the study. In group 1, intestinal histology revealed no significant changes between T0 and T1 specimens. In contrast, in group 2, graft histology revealed moderate to severe rejection at T1 in all specimens. In contrast to group 1, serum levels of total bile acids increased significantly in group 2 at T1 compared with baseline (P=0.001). The increase was due to secondary bile acids which were significantly higher at T1 compared with baseline (P=0.0003). In contrast, secondary bile acids increased but not significantly at T1 in group 1 compared with baseline (P=0.056). CONCLUSION: Our study suggests that total and secondary serum bile acids may be a useful diagnostic tool for the diagnosis of acute intestinal rejection.

Published
2009
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11. Urinary cytotoxic molecular markers for a noninvasive diagnosis in acute renal transplant rejection*

Author

Sophie Felix, Gérard Rifle, Christophe Ferrand, Jean-Michel Rebibou, Philippe Saas, Jean-Marc Chalopin, Pierre Tiberghien, Maria Yannaraki, Patrick Hervé, Anne Duperrier, Didier Ducloux, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Saas, Philippe, and Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)

Subjects
Graft Rejection, Male, Nephrology, Pathology, MESH: Membrane Glycoproteins, 030232 urology & nephrology, MESH: Urinary Tract Infections, 030230 surgery, Gastroenterology, Granzymes, MESH: Kidney Transplantation, Postoperative Complications, 0302 clinical medicine, Chronic allograft nephropathy, MESH: Postoperative Complications, MESH: Reverse Transcriptase Polymerase Chain Reaction, Lymphocytes, MESH: Serine Endopeptidases, Kidney transplantation, Kidney, Membrane Glycoproteins, MESH: Middle Aged, MESH: Pore Forming Cytotoxic Proteins, Reverse Transcriptase Polymerase Chain Reaction, Serine Endopeptidases, MESH: Tumor Necrosis Factors, Middle Aged, MESH: Predictive Value of Tests, 3. Good health, MESH: Reproducibility of Results, medicine.anatomical_structure, Real-time polymerase chain reaction, Acute Disease, Cytomegalovirus Infections, Tumor Necrosis Factors, Urinary Tract Infections, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pore Forming Cytotoxic Proteins, medicine.medical_specialty, Fas Ligand Protein, [SDV.IMM] Life Sciences [q-bio]/Immunology, Urinary system, MESH: Graft Rejection, Sensitivity and Specificity, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, MESH: Transplantation, Homologous, medicine, Humans, Transplantation, Homologous, RNA, Messenger, MESH: RNA, Messenger, MESH: Granzymes, Transplantation, MESH: Humans, Perforin, business.industry, MESH: Biological Markers, Reproducibility of Results, MESH: Cytomegalovirus Infections, medicine.disease, Kidney Transplantation, MESH: Male, MESH: Sensitivity and Specificity, MESH: Fas Ligand Protein, MESH: Perforin, MESH: Lymphocytes, Complication, business, MESH: Female, Biomarkers
Abstract

International audience; Perforin (P), Granzyme B (GB) and Fas-Ligand (FAS-L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty-two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas-L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas-L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas-L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.

Published
2006
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12. Stable long-term pulmonary function after fludarabine, antithymocyte globulin and i.v. BU for reduced-intensity conditioning allogeneic SCT

Author

P. Germaud, Mohamad Mohty, Patricia Lemarchand, Florent Malard, Béatrice Delasalle, Philippe Moreau, Patrice Chevallier, Thierry Guillaume, Arnaud Chambellan, Jacques Delaunay, S. Dirou, Service de Pneumologie, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut du Thorax, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service Hématologie Clinique, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FM was supported by educational grants from the 'Association for Training, Education and Research in Hematology, Immunology and Transplantation' (ATERHIT). We also thank the 'Re'gion Pays de Loire', the 'Association pour la Recherche sur le Cancer', the 'Fondation de France', the 'Fondation contre la Leuce' mie', the 'Agence de Biome' decine', the 'Association Cent pour Sang la Vie', the 'Association Laurette Fuguain', the IRGHET and the 'Ligue Contre le Cancer' (Comite' s Grand-Ouest) for their generous and continuous support for our clinical and basic research work. Our group is supported by several grants from the French National Cancer Institute (PHRC, INCa to MM)., Lemarchand, Patricia, Université de Nantes (UN)-Institut du Thorax-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Lung Diseases, Male, Vital capacity, Transplantation Conditioning, MESH: Administration, Intravenous, MESH: Busulfan, MESH: Respiratory Function Tests, Gastroenterology, Pulmonary function testing, MESH: Lung Diseases, 0302 clinical medicine, MESH: Antilymphocyte Serum, hemic and lymphatic diseases, Medicine, Cumulative incidence, MESH: Transplantation Conditioning, MESH: Aged, education.field_of_study, MESH: Middle Aged, pulmonary function, Hematology, MESH: Follow-Up Studies, Middle Aged, MESH: Hematologic Diseases, Fludarabine, Respiratory Function Tests, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Vidarabine, Administration, Intravenous, Female, MESH: Immunosuppressive Agents, MESH: Stem Cell Transplantation, Immunosuppressive Agents, Vidarabine, medicine.drug, Adult, medicine.medical_specialty, MESH: Myeloablative Agonists, Population, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Lymphocyte Depletion, Article, 03 medical and health sciences, FEV1/FVC ratio, Young Adult, Internal medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, education, Busulfan, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Antilymphocyte Serum, Retrospective Studies, MESH: Lymphocyte Depletion, Transplantation, MESH: Humans, business.industry, MESH: Adult, MESH: Retrospective Studies, Myeloablative Agonists, Hematologic Diseases, MESH: Male, Surgery, ATG, Regimen, business, MESH: Female, reduced-intensity conditioning, 030215 immunology, Follow-Up Studies, Stem Cell Transplantation
Abstract

International audience; Lung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT.

Published
2014
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13. Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia

Author

Récher, C., Béné, M. C., Lioure, B., Pigneux, A., Vey, N., Delaunay, J., Luquet, I., Hunault, M., Guyotat, D., Bouscary, D., Fegueux, N., Jourdan, E., Lissandre, S., Escoffre-Barbe, M., Bonmati, C., Randriamalala, E., Guièze, R., Ojeda-Uribe, M., Dreyfus, F., Harousseau, J. L., Cahn, J. Y., Ifrah, N., Guardiola, P., Renseigné, Non, Centre hospitalier universitaire de Nantes (CHU Nantes), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), On behalf of the IFM group, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), 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), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
Oncology, Cancer Research, MESH: Remission Induction, Myeloid, medicine.medical_treatment, Hematopoietic stem cell transplantation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, polycyclic compounds, Young adult, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, Remission Induction, Age Factors, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Follow-Up Studies, Middle Aged, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, MESH: Antineoplastic Combined Chemotherapy Protocols, medicine.anatomical_structure, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, Myeloid leukaemia, MESH: Leukemia, Myeloid, Acute, MESH: Daunorubicin, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Daunorubicin, 03 medical and health sciences, Young Adult, Internal medicine, medicine, MESH: Transplantation, Homologous, Idarubicin, Humans, Transplantation, Homologous, neoplasms, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, MESH: Adolescent, MESH: Age Factors, MESH: Humans, business.industry, MESH: Idarubicin, MESH: Adult, medicine.disease, Surgery, carbohydrates (lipids), Transplantation, business, Follow-Up Studies
Abstract

Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia

Published
2014
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14. Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study

Author

Marie-Christiane Vekemans, Martine Escoffre, Norbert Ifrah, Hervé Dombret, Delphine Rea, Aline Tanguy-Schmidt, Xavier Thomas, Sandrine Hayette, Philippe Rousselot, André Delannoy, Yves Chalandon, Jean-Paul Vernant, Jean-Yves Cahn, Françoise Huguet, Jean-Michel Cayuela, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Laboratoire central d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Biologie Moléculaire, Hospices Civils de Lyon (HCL), 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], Hôpital de Jolimont, Haine-Saint-Paul and Cliniques Universitaires St Luc, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Hôpital Edouard Herriot [CHU - HCL]

Subjects
Oncology, Male, Time Factors, medicine.medical_treatment, MESH: Piperazines, Hematopoietic stem cell transplantation, Acute lymphoblastic leukemia, MESH: Philadelphia Chromosome, Piperazines, MESH: Unrelated Donors, MESH: Benzamides, 0302 clinical medicine, hemic and lymphatic diseases, Philadelphia Chromosome, ddc:616, Philadelphia Chromosome Positive, MESH: Middle Aged, Stem cell transplantation, Age Factors, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Follow-Up Studies, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Transplantation, Autologous, 3. Good health, Survival Rate, Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/therapy, 030220 oncology & carcinogenesis, Benzamides, Imatinib Mesylate, Female, Unrelated Donors, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH: Survival Rate, Pyrimidines/administration & dosage/adverse effects, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Philadelphia chromosome, Transplantation, Autologous, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Survival rate, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Age Factors, Transplantation, MESH: Humans, business.industry, MESH: Time Factors, Imatinib, Benzamides/administration & dosage/adverse effects, MESH: Adult, medicine.disease, Piperazines/administration & dosage/adverse effects, MESH: Male, Surgery, Clinical trial, Imatinib mesylate, Pyrimidines, MESH: Pyrimidines, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Antineoplastic Agents/administration & dosage/adverse effects, business, MESH: Female, 030215 immunology, Follow-Up Studies
Abstract

International audience; We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response).

Published
2013
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15. Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor

Author

Michel Godin, Pierre Aucouturier, Arnaud François, Catherine Johanet, Hanna Debiec, Sophie Ferlicot, Pierre Ronco, Dominique Guerrot, M. Hanoy, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Service de pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service immunologie, Centre de Recherche Saint-Antoine (UMRS893), The work was supported by grants from Fondation pour la Recherche Médicale (Equipe FRM2012) and by grant from Agence Nationale pour la Recherche (ANR-07-hysio-016-01)., RONCO, Pierre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Pathology, medicine.medical_specialty, Glomerular deposits, MESH: Glomerulonephritis, Membranous, 030232 urology & nephrology, Biology, Brief Communication, Glomerulonephritis, Membranous, MESH: Kidney Transplantation, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Membranous nephropathy, Recurrence, MESH: Postoperative Complications, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biopsy, medicine, MESH: Receptors, Phospholipase A2, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Kidney transplantation, 030304 developmental biology, MESH: Immunoglobulin G, 0303 health sciences, Proteinuria, MESH: Humans, MESH: Middle Aged, medicine.diagnostic_test, Receptors, Phospholipase A2, Glomerulonephritis, General Medicine, Middle Aged, medicine.disease, Kidney Transplantation, MESH: Male, 3. Good health, MESH: Recurrence, Transplantation, Nephrology, Immunoglobulin G, Monoclonal, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine.symptom
Abstract

International audience; Up to 80% of patients with idiopathic membranous nephropathy have non-complement-fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). Membranous nephropathy recurs in approximately 40% of patients after kidney transplantation, but the mechanism is unknown. Here, we describe a patient with recurrent membranous nephropathy 13 days after kidney transplantation whose graft biopsy specimen showed granular staining for C3, C5b-9, C1q, and IgG3κ; electron microscopy revealed subepithelial nonorganized deposits. A search for hematologic disorders was negative. Retrospective evaluation of a biopsy sample from the native kidney revealed a similar pattern: monotypic IgG3κ deposits together with C3, C1q, and C5b-9. Glomerular deposits contained PLA2R in both the graft and the native kidney, suggesting that the recurrence was the result of circulating anti-PLA2R antibodies binding to PLA2R antigen expressed on donor podocytes. Confocal analysis of anti-PLA2R and antihuman IgG3 showed co-localization, and the patient had IgG3κ-restricted circulating anti-PLA2R antibodies. Treatment with rituximab stabilized both proteinuria and serum creatinine, and circulating anti-PLA2R became undetectable. In summary, this case of recurrent membranous nephropathy in a graft suggests that circulating monoclonal anti-PLA2R IgG3κ caused the disease and activated complement by the classic pathway.

Published
2012
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16. No increased mortality from donor or recipient hepatitis B- and/or hepatitis C-positive serostatus after related-donor allogeneic hematopoietic cell transplantation

Author

Min Chen, Brian J. Bolwell, Matthew Carabasi, Karen K. Ballen, F. Al Mohareb, Jo Anne H. Young, John R. Wingard, Jan Storek, Gregory A. Hale, Robert Peter Gale, Mary M. Horowitz, M Aljurf, Vikas Gupta, Marcie Tomblyn, Richard T. Maziarz, Ronald E. Gress, Manisha Kukreja, Per Ljungman, J. Y. Cahn, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Princess Margaret Hospital, and University of Toronto

Subjects
Male, MESH: Tissue Donors, medicine.medical_treatment, Hepacivirus, Hematopoietic stem cell transplantation, medicine.disease_cause, 0302 clinical medicine, MESH: Child, MESH: Hepacivirus, MESH: Incidence, Child, MESH: Middle Aged, biology, Incidence, Hematopoietic Stem Cell Transplantation, Hepatitis C, MESH: Transplantation, Hepatitis B, Middle Aged, MESH: Infant, Tissue Donors, 3. Good health, MESH: Hepatitis B virus, Infectious Diseases, MESH: Young Adult, 030220 oncology & carcinogenesis, Child, Preschool, Female, Adult, Hepatitis B virus, Allogeneic transplantation, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Young Adult, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Hepatitis C, Transplantation, MESH: Humans, MESH: Hepatitis B, business.industry, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Male, Immunology, Serostatus, business, MESH: Female, 030215 immunology
Abstract

International audience; Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen-identical related-donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow-up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment-related mortality, survival, graft-versus-host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant.

Published
2012
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17. Allogeneic hematopoietic cell transplantation for advanced polycythemia vera and essential thrombocythemia

Author

Matt Kalaycio, Mukta Arora, Joseph H. Antin, Joerg Halter, Richard T. Maziarz, Wael Saber, Matthew Carabasi, Kwang Woo Ahn, Harry C. Schouten, Vikas Gupta, Ann E. Woolfrey, Mahmoud Aljurf, Brian J. Bolwell, David L. Porter, Ian D. Lewis, Xiaochun Zhu, H. Joachim Deeg, Jean-Yves Cahn, Mary M. Horowitz, Philip L. McCarthy, Gregory A. Hale, Bipin N. Savani, Biju George, Mehdi Hamadani, Steven Z. Pavletic, Jorge E. Cortes, Ed Copelan, Baldeep Wirk, Karen K. Ballen, Mayo Clinic, the Cleveland Clinic Foundation, Cleveland Clinic, St Jude Children's Research Hospital, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), University Hospital Basel [Basel], Roswell Park Cancer Institute [Buffalo], Division of Haematology, University of Toronto-Princess Margaret Hospital, University of Toronto, Institut d'Astrophysique de Paris (IAP), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Interne Geneeskunde, and RS: GROW - School for Oncology and Reproduction

Subjects
Male, Transplantation Conditioning, Neutrophils, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, PV, MESH: Neutrophils, Gastroenterology, MESH: Polycythemia Vera, 0302 clinical medicine, Polycythemia vera, Recurrence, Cumulative incidence, Longitudinal Studies, MESH: Longitudinal Studies, Polycythemia Vera, MESH: Transplantation Conditioning, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, MESH: Splenomegaly, 030220 oncology & carcinogenesis, MESH: Survival Analysis, Acute Disease, Splenectomy, MESH: Acute Disease, Female, Thrombocythemia, Essential, Adult, medicine.medical_specialty, MESH: Myeloablative Agonists, Platelet Engraftment, MESH: Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Splenectomy, Article, 03 medical and health sciences, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Myelofibrosis, MESH: Hematopoietic Stem Cell Transplantation, Transplantation, Neutrophil Engraftment, MESH: Humans, Essential thrombocythemia, business.industry, MESH: Adult, Myeloablative Agonists, medicine.disease, Survival Analysis, MESH: Male, Surgery, MESH: Recurrence, Splenomegaly, MESH: Thrombocythemia, Essential, business, ET, MESH: Female, 030215 immunology
Abstract

Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splenectomy. Most patients (69% for ET and 67% for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus-host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47% and 71%/48% for ET and PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS. American Society for Blood and Marrow Transplantation.

Published
2012
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18. Loss of central and peripheral CD8+ T-cell tolerance to HFE in mouse models of human familial hemochromatosis

Author

Boucherma, Rachid, Kridane-Miledi, Hédia, Vives, Francina Langa, Vauchy, Charline, Borg, Christophe, Kleinclauss, François, Fiette, Laurence, Tiberghien, Pierre, Lemonnier, François, Rohrlich, Pierre, Huetz, François, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Immunité Cellulaire Antivirale, Institut Pasteur [Paris], Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Histopathologie humaine et Modèles animaux, Département de pédiatrie, Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)

Subjects
MESH: Hemochromatosis, MESH: Genetic Diseases, Inborn, MESH: Immune Tolerance, [SDV.IMM] Life Sciences [q-bio]/Immunology, Mutation, Missense, Graft vs Host Disease, MESH: Graft vs Host Disease, Thymus Gland, CD8-Positive T-Lymphocytes, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, Mice, MESH: Skin, Immune Tolerance, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH: Animals, Hemochromatosis Protein, MESH: Mice, Skin, Mice, Knockout, MESH: Mutation, Missense, MESH: Humans, MESH: Mice, Inbred DBA, Histocompatibility Antigens Class I, Genetic Diseases, Inborn, Membrane Proteins, MESH: Thymus Gland, MESH: Amino Acid Substitution, MESH: CD8-Positive T-Lymphocytes, Disease Models, Animal, Amino Acid Substitution, Mice, Inbred DBA, [SDV.IMM]Life Sciences [q-bio]/Immunology, Hemochromatosis, MESH: Membrane Proteins, MESH: Disease Models, Animal
Abstract

International audience; HFE, an MHC class Ib molecule that controls iron metabolism, can be directly targeted by cytotoxic TCR αβ T lymphocytes. Transgenic DBA/2 mice expressing, in a Rag 2 KO context, an αβ TCR that directly recognizes mouse HFE (mHFE) were created to further explore the interface of HFE with the immune system. TCR-transgenic mHfe WT mice deleted mHFE-reactive T cells in the thymus, but a fraction of reprogrammed cells were able to escape deletion. In contrast, TCR-transgenic mice deprived of mHFE molecules (mHfe KO mice) or expressing a C282→Y mutated mHFE molecule - the most frequent mutation associated with human hereditary hemochromatosis - positively selected mHFE-reactive CD8(+) T lymphocytes and were not tolerant toward mHFE. By engrafting these mice with DBA/2 WT (mHFE(+)) skin, it was established, as suspected on the basis of similar engraftments performed on DBA/2 mHfe KO mice, that mHFE behaves as an autonomous skin-associated histocompatibility antigen, even for mHFE-C282→Y mutated mice. By contrast, infusion of DBA/2 mHFE(+) mice with naïve mHFE-reactive transgenic CD8(+) T lymphocytes did not induce GVHD. Thus, tolerance toward HFE in mHfe WT mice can be acquired at either thymic or peripheral levels but is disrupted in mice reproducing human familial hemochromatosis.

Published
2012
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19. Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Author

Jean-Henri Bourhis, Frédéric Garban, Mohamad Mohty, Nathalie Contentin, Gérard Socié, Sylvie François, Mauricette Michallet, Nathalie Fegueux, Madalina Uzunov, Serge Koscielny, Natacha Maillard, Ibrahim Yakoub-Agha, Simona Lapusan, Didier Blaise, Claire Fabre, Reza Tabrizi, Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), UAM Allogreffes de CSH, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Département de cancérologie et d'hématologie, and CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon

Subjects
Male, Oncology, MESH: Tissue Donors, MESH: Registries, MESH: Multiple Myeloma, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Cause of Death, 0302 clinical medicine, Recurrence, Cause of Death, Registries, Prospective cohort study, Multiple myeloma, Cause of death, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Mortality rate, Age Factors, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, Tissue Donors, MESH: Transplantation, Autologous, 3. Good health, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, Female, Multiple Myeloma, Adult, medicine.medical_specialty, Transplantation, Autologous, MESH: Prognosis, Young Adult, 03 medical and health sciences, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Autologous transplantation, Survival analysis, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Age Factors, MESH: Humans, business.industry, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Survival Analysis, MESH: Male, Surgery, MESH: Recurrence, Transplantation, MESH: Morbidity, Original Articles and Brief Reports, Morbidity, business, MESH: Female, 030215 immunology
Abstract

International audience; BACKGROUND: How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). DESIGN AND METHODS: This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure. RESULTS: Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2-132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39-57 %) and 27% (95% CI 19-36), respectively. Eighteen patients (12%) experienced grade III-IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10-22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor's age ≤ 50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor's age ≤ 50 years and full chimerism were independent prognostic factors for better outcome. CONCLUSIONS: We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor's age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies.

Published
2012
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20. Reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation in patients over 60 years: a report from the SFGM-TC

Author

Sylvie François, Agnes Buzyn, Mauricette Michallet, Nicole Gratecos, Didier Blaise, François Guilhot, Richard Szydlo, Reza Tabrizi, Mohamad Mohty, Gérard Socié, Nathalie Contentin, Madalina Uzunov, Nathalie Fegueux, Jacques-Olivier Bay, Patrice Chevallier, Anne Huynh, Simona Lapusan, Jean-Yves Cahn, Ibrahim Yakoub-Agha, Sébastien Maury, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut de Chimie du CNRS (INC), Service Hématologie, Centre Hospitalier Universitaire de Nice (CHU Nice), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), UAM Allogreffes de CSH, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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], Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Institut de Chimie des Milieux et Matériaux de Poitiers ( IC2MP ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), CHU Nice, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Hematology, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Toulouse III - Paul Sabatier ( UPS ), CRLCC Jean Perrin, Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Hematology, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes

Subjects
Male, MESH: Tissue Donors, Multivariate analysis, Transplantation Conditioning, MESH : Retrospective Studies, MESH : Transplantation Conditioning, medicine.medical_treatment, MESH : Aged, Hematopoietic stem cell transplantation, Disease, Allo-HSCT, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Medicine, MESH : Female, MESH : Tissue Donors, MESH: Transplantation Conditioning, MESH: Aged, MESH: Middle Aged, Age Factors, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Follow-Up Studies, Middle Aged, SFGM-TC, MESH : Survival Rate, MESH : Risk Factors, Tissue Donors, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Reduced Intensity Conditioning, Hematologic Neoplasms, MESH : Disease-Free Survival, Female, MESH : Hematologic Neoplasms, medicine.medical_specialty, MESH: Survival Rate, MESH : Transplantation, Homologous, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Age, MESH : Hematopoietic Stem Cell Transplantation, Internal medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH : Middle Aged, In patient, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Age Factors, Transplantation, MESH: Humans, business.industry, MESH : Humans, RIC, Complete remission, MESH : Follow-Up Studies, MESH: Retrospective Studies, Confidence interval, MESH: Male, Surgery, Elderly patients, Relative risk, MESH: Disease-Free Survival, MESH : Age Factors, business, MESH: Female, 030215 immunology, Follow-Up Studies, MESH: Hematologic Neoplasms
Abstract

International audience; This retrospective multicenter report assessed the outcome of 600 patients with hematologic diseases older than 60 years who received reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the specific aim to compare outcomes of patients between 60 and 65 years old (N = 493) with those older than 65 years (N = 107). Except for donor age, there were no significant differences between the groups regarding patients, diseases, and allo-HSCT characteristics. At time of RIC allo-HSCT, 276 patients (46%) were in complete remission. With a median follow-up of 22.8 and 23.7 months in the younger and the older groups, respectively, 2-year relapse, nonrelapse mortality, disease-free survival, and overall survival rates were similar in both groups (29.6% vs. 20.4%; 29.9% vs. 34.6%; 40.6% vs. 46.7%; 49.2% vs. 50.2%, respectively; P = NS for all comparisons). In a Cox multivariate analysis, after adjustment for disease and transplant factors, age per se was not an adverse factor for survival (relative risk = 1.08; 95% confidence interval, 0.81-1.44, P = .62). We conclude that in selected patients, RIC allo-HSCT could be offered to patients over 65 years old.

Published
2012
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21. Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study

Author

Martin Bornhäuser, Donald Bunjes, Jean-Yves Cahn, Mark R. Litzow, Corey Cutler, Ann A. Jakubowski, David I. Marks, Robert J. Soiffer, Luis Isola, Philippe Armand, Jorge Sierra, Waleska S. Pérez, Hillard M. Lazarus, Daniel J. Weisdorf, Jürgen Finke, Vikas Gupta, Mei-Jie Zhang, Keith Stockerl-Goldstein, Steven M. Devine, Chadi Nabhan, Mitchell S. Cairo, Edward D. Ball, Bruce M. Camitta, Mahmoud Aljurf, Haesook T. Kim, Jacob M. Rowe, Bipin N. Savani, Christopher Bredeson, Paolo Bartolomeo, Paola Dal Cin, Victor Lewis, Effie W. Petersdorf, Richard T. Maziarz, M. Lynn Savoie, Joseph H. Antin, Joerg Halter, Harry C. Schouten, Edmund K. Waller, Philip L. McCarthy, Patrick J. Stiff, Alan M. Miller, Andrew S. Artz, Jane L. Liesveld, Thomas R. Klumpp, Medical College of Wisconsin, Division of Haematology, University of Toronto-Princess Margaret Hospital, University of Toronto, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Dipartimento di Ematologia, Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico, University Hospital Basel [Basel], University Hospital Carl Gustav Carus, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Interne Geneeskunde, and RS: GROW - School for Oncology and Reproduction

Subjects
Oncology, Male, Myeloid, medicine.medical_treatment, Abnormal Karyotype, Hematopoietic stem cell transplantation, 0302 clinical medicine, AML, hemic and lymphatic diseases, MESH: Aged, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Survival Rate, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, MESH: Abnormal Karyotype, MESH: Leukemia, Myeloid, Acute, Adult, medicine.medical_specialty, Allogeneic transplantation, Adolescent, MESH: Survival Rate, Karyotype, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Myelogenous, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Survival rate, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Adolescent, Transplantation, MESH: Humans, business.industry, Retrospective cohort study, MESH: Retrospective Studies, MESH: Adult, medicine.disease, MESH: Male, Surgery, MESH: Karyotyping, Karyotyping, MESH: Disease-Free Survival, business, MESH: Female, 030215 immunology, SCT
Abstract

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials. American Society for Blood and Marrow Transplantation.

Published
2012
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22. Risk factors for acute GVHD and survival after hematopoietic cell transplantation

Author

Vikas Gupta, Mary E.D. Flowers, Mukta Arora, Madan Jagasia, Alvaro Urbano-Ispizua, Stephanie J. Lee, Mei-Jie Zhang, Christopher Bredeson, Theresa Hahn, Philip L. McCarthy, Corey Cutler, Mark R. Litzow, Mitchell S. Cairo, Joseph H. Antin, Robert Peter Gale, Mary M. Horowitz, Steven Z. Pavletic, Nelson J. Chao, Jean-Yves Cahn, Michael Haagenson, Daniel J. Weisdorf, Brian J. Bolwell, Mayo Clinic, Department of Hematology, Hospital Universitario Virgen del Rocío [Sevilla], Medical College of Wisconsin, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Vanderbilt University [Nashville], Division of Haematology, University of Toronto-Princess Margaret Hospital, University of Toronto, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), and Roswell Park Cancer Institute [Buffalo]

Subjects
Male, MESH: Tissue Donors, Transplantation Conditioning, Clinical Trials and Observations, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Biochemistry, Gastroenterology, MESH: Unrelated Donors, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, MESH: Child, hemic and lymphatic diseases, Child, MESH: Transplantation Conditioning, MESH: Aged, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Hematology, Total body irradiation, Middle Aged, MESH: Infant, Tissue Donors, 3. Good health, Survival Rate, surgical procedures, operative, MESH: Young Adult, 030220 oncology & carcinogenesis, Child, Preschool, Histocompatibility, Hematologic Neoplasms, Acute Disease, MESH: Acute Disease, Female, Unrelated Donors, MESH: Whole-Body Irradiation, Whole-Body Irradiation, Adult, medicine.medical_specialty, MESH: Survival Rate, Adolescent, Immunology, MESH: Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, MESH: Transplantation, Homologous, medicine, Transplantation, Homologous, Humans, Survival rate, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, business.industry, Siblings, MESH: Child, Preschool, Infant, MESH: Retrospective Studies, MESH: Adult, Cell Biology, medicine.disease, MESH: Male, MESH: Histocompatibility, MESH: Siblings, Surgery, Transplantation, Regimen, Graft-versus-host disease, business, MESH: Female, MESH: Hematologic Neoplasms, 030215 immunology
Abstract

Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.

Published
2012
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23. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies

Author

Laurence Clement, Yves Beguin, Alain Duhamel, Pierre Fenaux, Eric Deconinck, Marie-Thérèse Rubio, Ibrahim Yakoub-Agha, Aline Schmidt-Tanguy, Claude-Eric Bulabois, Pierre Bories, Jean-Pierre Marolleau, Gandhi Damaj, Jean El Cheikh, Mohamad Mohty, Lionel Ades, Stephane Vigouroux, Zora Marjanovic, Faeyzeh Legrand, Natacha Maillard, Charles Dauriac, Anne Huynh, Jérôme Cornillon, Jacques-Olivier Bay, Gaelle Guillerm, Sophie Park, Nathalie Fegueux, Mauricette Michallet, Marie Robin, Alice Garnier, Federico Garnier, Saas, Philippe, CHU Amiens-Picardie, Centre d'Etude et Recherche en Informatique Médicale, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie greffe [Saint-Louis], 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), Service d'Hématologie, Université de Liège, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Service Hématologie, CHU Strasbourg, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, 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), Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Agence de la biomédecine [Saint-Denis la Plaine], Hôpital Avicenne [AP-HP], UAM Allogreffes de CSH, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CRLCC Jean Perrin, CHU Nice, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Hôpital Jean Bernard, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CHU Cochin [AP-HP], Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Toulouse III - Paul Sabatier (UT3), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest]

Subjects
Male, Oncology, Cancer Research, MESH: Combined Modality Therapy, MESH : Retrospective Studies, MESH : Induction Chemotherapy, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Treatment Outcome, MESH: Antimetabolites, Antineoplastic, MESH: Middle Aged, MESH : Antimetabolites, Antineoplastic, Hematopoietic Stem Cell Transplantation, Induction Chemotherapy, Middle Aged, Combined Modality Therapy, MESH: Induction Chemotherapy, 3. Good health, Treatment Outcome, International Prognostic Scoring System, 030220 oncology & carcinogenesis, Azacitidine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Stem cell, MESH: Myelodysplastic Syndromes, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, MESH : Azacitidine, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Transplantation, Homologous, MESH : Male, MESH: Azacitidine, MESH : Myelodysplastic Syndromes, MESH : Treatment Outcome, 03 medical and health sciences, MESH : Hematopoietic Stem Cell Transplantation, Internal medicine, parasitic diseases, medicine, Overall survival, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH: Hematopoietic Stem Cell Transplantation, Retrospective Studies, MESH: Humans, business.industry, Myelodysplastic syndromes, MESH : Humans, Induction chemotherapy, Retrospective cohort study, MESH: Retrospective Studies, medicine.disease, MESH: Male, Transplantation, Myelodysplastic Syndromes, MESH : Combined Modality Therapy, business, MESH: Female, 030215 immunology
Abstract

Purpose To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). Patients and Methods Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. Results With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. Conclusion With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.

Published
2012
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24. Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

Author

E. Deconinck, Faezeh Legrand, Frédéric Grenouillet, Frédéric Dalle, Fabrice Larosa, Philippe Saas, Laurence Millon, Pierre Rohrlich, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), and Université de Bourgogne (UB)

Subjects
Male, medicine.medical_treatment, MESH : Cryptosporidium parvum, Cryptosporidiosis, Graft vs Host Disease, Hematopoietic stem cell transplantation, Azithromycin, Gastroenterology, 0302 clinical medicine, immune system diseases, MESH : Thiazoles, MESH: Animals, MESH : Female, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH : Azithromycin, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Antibacterial agent, 0303 health sciences, MESH: Middle Aged, biology, MESH : Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, MESH: Immunosuppression, Nitazoxanide, Immunosuppression, Hematology, Middle Aged, MESH : Adult, Nitro Compounds, MESH : Diagnosis, Differential, 3. Good health, Cryptosporidium parvum, surgical procedures, operative, MESH: Young Adult, Female, medicine.symptom, MESH : Lymphopenia, medicine.drug, Adult, medicine.medical_specialty, MESH : Transplantation, Homologous, MESH : Male, MESH : Young Adult, MESH: Thiazoles, MESH: Graft vs Host Disease, Asymptomatic, MESH: Lymphopenia, Diagnosis, Differential, 03 medical and health sciences, Young Adult, MESH: Diagnosis, Differential, Internal medicine, MESH: Azithromycin, Lymphopenia, MESH : Hematopoietic Stem Cell Transplantation, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH : Cryptosporidiosis, MESH: Hematopoietic Stem Cell Transplantation, Immunosuppression Therapy, Transplantation, MESH: Humans, 030306 microbiology, business.industry, MESH: Cryptosporidiosis, MESH : Humans, MESH: Adult, biology.organism_classification, MESH: Male, Thiazoles, Immunology, MESH : Immunosuppression, MESH: Cryptosporidium parvum, MESH : Animals, business, MESH: Female
Abstract

International audience; Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

Published
2011
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25. Retrospective study of allogeneic haematopoietic stem-cell transplantation for myelofibrosis

Author

Jérôme Cornillon, A. Cabrespine, J.-O. Bay, Bruno Cassinat, R. Peffault de Latour, Raphaël Porcher, Severine Lissandre, J.Y. Cahn, V. Cacheux, Gérard Socié, Marie Robin, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10

Subjects
Transplantation Conditioning, Graft vs Host Disease, Gastroenterology, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, MESH: Transplantation Conditioning, MESH: Aged, Hematology, Leukemia, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Middle Aged, 3. Good health, Fludarabine, Haematopoiesis, surgical procedures, operative, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, MESH: Primary Myelofibrosis, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH: Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, MESH: Leukemia, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Myelofibrosis, Survival analysis, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Adolescent, Transplantation, MESH: Humans, business.industry, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Survival Analysis, Surgery, Graft-versus-host disease, Primary Myelofibrosis, business, 030215 immunology
Abstract

International audience; Allogeneic haematopoietic stem-cell transplantation (HSCT) is the only curative treatment for myelofibrosis. We retrospectively analyzed the outcome of patients who underwent allogeneic HSCT, 1994-2008, and the potential risk factors affecting non-relapse mortality (NRM), OS and relapse-free survival (RFS). A total of 39 patients, 15-65 (median 49) years old, diagnosed with primary (n=27) or secondary (n=12) myelofibrosis underwent HSCT (25 related and 14 unrelated). In ten patients, disease had transformed into acute leukaemia. Lille prognosis score was low for 9, intermediate for 16 and high for 14 patients. The conditioning regimen was myeloablative (MAC) for 15 and reduced-intensity (RIC) fludarabine-based for 24, with successful engraftment in 38 patients. A total of 31 patients developed grade I-IV GvHD; 19 developed chronic GvHD. The 3-year OS, RFS and NRM rates (95% confidence interval) were 60% (42-74), 54% (37-59) and 30% (30-45), respectively.

Published
2011
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26. Immunomonitoring of graft-versus-host minor histocompatibility antigen correlates with graft-versus-host disease and absence of relapse after graft

Author

David Laurin, Martine Pernollet, Agnès Moine, Jean-Claude Bensa, Joel Plumas, Jean-Yves Cahn, Frédéric Garban, Dalil Hannani, 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), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Bases moléculaires de la progression tumorale -Groupe de Recherche sur les Lymphomes, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR73, Laboratoires Immunocytologie et HLA, département d'Immunologie Cellulaire, EFS, Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), TheREx, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Département de cancérologie et d'hématologie, and CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon

Subjects
MESH: Minor Histocompatibility Antigens, Male, MESH: Tissue Donors, Transplantation Conditioning, medicine.medical_treatment, Graft vs Host Disease, Disease, Hematopoietic stem cell transplantation, MESH: Peripheral Blood Stem Cell Transplantation, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, 0302 clinical medicine, immune system diseases, Recurrence, T-Lymphocyte Subsets, Minor histocompatibility antigen, Immunology and Allergy, MESH: Bone Marrow Transplantation, MESH: Transplantation Conditioning, Bone Marrow Transplantation, 0303 health sciences, MESH: Middle Aged, ELISPOT, MESH: Enzyme-Linked Immunosorbent Assay, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, MESH: Transplantation, MESH: Follow-Up Studies, Middle Aged, MESH: CD8-Positive T-Lymphocytes, Tissue Donors, 3. Good health, Leukemia, surgical procedures, operative, MESH: Young Adult, Hematologic Neoplasms, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, Adult, Adolescent, MESH: Interferon-gamma, Immunology, MESH: Graft vs Host Disease, Enzyme-Linked Immunosorbent Assay, Graft vs Leukemia Effect, Minor Histocompatibility Antigens, 03 medical and health sciences, Interferon-gamma, Young Adult, Antigen, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, 030304 developmental biology, MESH: Adolescent, Peripheral Blood Stem Cell Transplantation, Transplantation, MESH: Humans, business.industry, MESH: Adult, MESH: Graft vs Leukemia Effect, medicine.disease, MESH: Male, Histocompatibility, MESH: Recurrence, Graft-versus-host disease, Feasibility Studies, business, MESH: Feasibility Studies, MESH: Female, 030215 immunology, MESH: Hematologic Neoplasms, Follow-Up Studies
Abstract

International audience; BACKGROUND: After HLA-identical hematopoietic stem cell transplantation, minor histocompatibility (mH) antigen alloreactivity plays a dominant role in the development of graft-versus-host disease (GVHD) and graft versus leukemia (GVL). STUDY DESIGN AND METHODS: We have analyzed the mH alloreactivity (enzyme-linked immunospot [ELISpot] for interferon-gamma[IFN-gamma] assay) from 24 donor/recipient pairs over a period of 2 years of follow-up and correlated such alloreactivity with the development of GVHD or absence of relapse. Circulating specific T cells anti-mH with multimer HLA-peptides were also studied. RESULTS: We show by ELISpot IFN-gamma assay that alloreactivity during the first 3 months from donor versus recipient or donor versus mismatched identified mH antigens is associated with acute GVHD and GVL effect. In addition, we demonstrate that the donor-versus-recipient reactivity observed after the third month is highly associated with chronic GVHD and GVL (p = 0.0007). Finally, we show by multimer HLA-peptide assay that mH epitope-specific T cells present after 3 months are statistically related to the GVL effect. CONCLUSIONS: Our results provide a robust method to monitor mH antigen graft-versus-host reaction and suggest that current identified mH have predictive value on GVHD and GVL.

Published
2009
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27. Performance of the new mycophenolate assay based on IMPDH enzymatic activity for pharmacokinetic investigations and setup of Bayesian estimators in different populations of allograft recipients

Author

Ingrid Domke, Marco Tiberi, Evelyne Jaqz-Aigrain, Pierre Marquet, Jean Debord, Christiane Knoop, Yvon Lebranchu, François-Ludovic Sauvage, Franck Saint-Marcoux, Aurélie Prémaud, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Paediatric Pharmacology and Pharmacogenetics, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de chirurgie cardiovasculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Roche SAS, Roche Diagnostics GmbH, This study was sponsored by Roche Diagnostics., and Marquet, Pierre

Subjects
Male, MESH: Drug Interactions, Mycophenolate, 030226 pharmacology & pharmacy, High-performance liquid chromatography, MESH: Cyclosporine, MESH: Kidney Transplantation, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Liquid chromatography–mass spectrometry, IMP dehydrogenase, Bayesian estimators, MESH: Child, Pharmacology (medical), Drug Interactions, Child, Chemistry, Graft Survival, Area under the curve, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Anti-Bacterial Agents, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 030220 oncology & carcinogenesis, Cyclosporine, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, MESH: Graft Survival, Urology, Mycophenolic acid, Tacrolimus, Article, 03 medical and health sciences, Pharmacokinetics, MESH: Anti-Bacterial Agents, medicine, MESH: Tacrolimus, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, LC-MS/MS, MESH: Mycophenolic Acid, Pharmacology, Sirolimus, Chromatography, MESH: Humans, Dose-Response Relationship, Drug, MESH: Adult, Mycophenolic Acid, Kidney Transplantation, MESH: Male, monitoring, enzymatic assay, MESH: Sirolimus, MESH: Female
Abstract

International audience; A new mycophenolate (MPA) assay based on the enzymatic activity of recombinant type II inosine monophosphate dehydrogenase (the pharmacological target of MPA) with excellent correlation with high-performance liquid chromatography has recently been released for the measurement of MPA plasma levels. This study aimed to (1) compare this new assay with liquid chromatography tandem mass spectrometry (LC-MS/MS) for MPA pharmacokinetic (PK) studies in different populations of allograft recipients given mycophenolate mofetil, (2) develop specific Bayesian estimators for this inhibition assay and test their accuracy, and (3) compare the resulting MPA area under the curve (AUC0-12h) estimates with those of Bayesian estimators developed based on the LC-MS/MS results. Sixty-four adult or pediatric, renal or lung transplant patients who were administered mycophenolate mofetil in association with cyclosporine, tacrolimus, or sirolimus at different post-transplant periods were enrolled as part of different PK studies. Eight hundred ninety-four patients' samples were analyzed in parallel with the enzymatic MPA assay and a reference LC-MS/MS method. Repeated analysis of quality control samples showed a mean difference of 6% between the 2 assays, whereas the results obtained in different populations of transplanted patients showed excellent correlation (r2 > 0.96) and small mean relative differences (2.0%-16.9%). The full profiles obtained with both assays were adequately fitted using either a 2-compartment model with 1 "gamma" absorption phase or a 1-compartment model with 2 gamma inputs. Several PK parameters were significantly affected by the analytical method used. Accurate Bayesian estimators could be specifically developed for the enzymatic MPA assay, using the same 3 concentration-time points (20 minutes, 1 hour, and 3 hours post dose) as with LC-MS/MS, with a median bias versus reference (trapezoidal) AUC0-12h values of -1.3% (range -45.2% to 40.4%), and 83% of the patients within +/-20% of the reference. These Bayesian estimates were significantly higher than those obtained with LC-MS/MS in patients on cyclosporine or sirolimus, but not in patients on tacrolimus.

Published
2009
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28. Allogeneic hematopoietic cell transplantation in human immunodeficiency virus-positive patients with hematologic disorders: a report from the center for international blood and marrow transplant research

Author

Minoo Battiwalla, Tanya L. Pedersen, Mary M. Horowitz, Ronald E. Gress, Jo Anne H. Young, Vikas Gupta, Armand Keating, Patricia Ribaud, Jill C. Thompson, Harry L. Atkins, Marilyn S. Pollack, Pierre Tiberghien, Marcie Tomblyn, Jan Storek, Division of Haematology, University of Toronto-Princess Margaret Hospital, University of Toronto, Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, University of Minnesota System-University of Minnesota System, Center for International Blood and Marrow Transplant Research (CIBMTR), Emory University [Atlanta, GA]-Medical College of Wisconsin, Clinical Haematology, Ottawa Hospital, Department of Medicine, Roswell Park Cancer Institute [Buffalo], Experimental Transplantation & Immunology Branch, National Institutes of Health [Bethesda] (NIH), Department of Pathology, The University of Texas Health Science Center at Houston (UTHealth), University of Calgary, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Center for International Blood and Marrow Transplant Research-Medical College of Wisconsin, Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
Male, Time Factors, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, MESH: Antiretroviral Therapy, Highly Active, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, MESH: Child, HIV Seropositivity, Prospective cohort study, Child, Human immunodeficiency virus, Standard treatment, Graft Survival, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Hematologic Diseases, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Bone marrow transplantation, MESH: Survival Rate, MESH: Graft Survival, MESH: Graft vs Host Disease, Disease-Free Survival, Article, 03 medical and health sciences, MESH: HIV Seropositivity, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Survival rate, Allogeneic, MESH: Hematopoietic Stem Cell Transplantation, Retrospective Studies, MESH: Adolescent, Transplantation, Neutrophil Engraftment, MESH: Humans, business.industry, MESH: Chronic Disease, MESH: Time Factors, Malignancy, Retrospective cohort study, MESH: Retrospective Studies, MESH: Adult, Hematologic Diseases, MESH: Male, Surgery, Clinical trial, Chronic Disease, MESH: Disease-Free Survival, business, MESH: Female, 030215 immunology
Abstract

International audience; The role of allogeneic hematopoietic cell transplantation (alloHCT) in human immunodeficiency virus (HIV)-positive patients is not known. Using the Center for International Blood and Marrow Transplant Research database, we retrospectively evaluated 23 HIV-positive patients undergoing matched sibling donor (n = 19) or unrelated donor (n = 4) alloHCT between 1987 and 2003. The median age at alloHCT was 32 years. Indications for alloHCT were diverse and included malignant (n = 21) and nonmalignant (n = 2) hematologic disorders. Nine patients (39%) underwent transplantation after 1996, the approximate year that highly active antiretroviral therapy became standard treatment. The median time to neutrophil engraftment was 16 days (range, 7 to 30 days), and the cumulative incidences of grade II-IV acute graft-versus-host disease (aGVHD) at 100 days, chronic GVHD (cGVHD), and survival at 2 years were 30% (95% confidence interval [CI] = 14% to 50%), 28% (95% CI = 12% to 48%), and 30% (95% CI = 14% to 50%), respectively. At a median follow-up of 59 months, 6 patients were alive. Survival appears to be better in the patients undergoing alloHCT after 1996; 4 of these 9 patients survived, compared with only 2 of 14 those undergoing transplantation before 1996. These data suggest that alloHCT is feasible for selected HIV-positive patients with malignant and nonmalignant disorders. Prospective studies are needed to evaluate the safety and efficacy of this modality in specific diseases in these patients.

Published
2009
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29. Evidence for anti-tumour effect of allogeneic haematopoietic SCT in cases without sustained donor engraftment

Author

Pierre Tiberghien, C. Faucher, Agnes Buzyn, M. Robin, Bruno Lioure, Etienne Daguindau, Eric Deconinck, M Kuentz, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), 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), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Unité de Transplantation et de Thérapie Cellulaire, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Saas, Philippe, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 )

Subjects
MESH: Tissue Donors, medicine.medical_treatment, MESH : Child, Preschool, Immunotherapy, Adoptive, Anti tumour, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, MESH : Graft Survival, MESH : Tissue Donors, MESH: Middle Aged, Hematology, Graft Survival, Hematopoietic Stem Cell Transplantation, MESH : Adult, Middle Aged, Tissue Donors, 3. Good health, Haematopoiesis, surgical procedures, operative, 030220 oncology & carcinogenesis, Child, Preschool, Hematologic Neoplasms, MESH: Immunotherapy, Adoptive, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, MESH : Hematologic Neoplasms, MESH: Transplantation Chimera, Adult, medicine.medical_specialty, Graft failure, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Graft Survival, MESH : Transplantation, Homologous, Graft vs Leukemia Effect, 03 medical and health sciences, MESH : Hematopoietic Stem Cell Transplantation, Internal medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH: Hematopoietic Stem Cell Transplantation, Transplantation, Transplantation Chimera, MESH: Humans, Hematopoietic cell, business.industry, MESH : Transplantation Chimera, MESH : Humans, MESH: Child, Preschool, MESH : Graft vs Leukemia Effect, MESH: Adult, Immunotherapy, MESH: Graft vs Leukemia Effect, Immunology, business, human activities, MESH : Immunotherapy, Adoptive, MESH: Hematologic Neoplasms, 030215 immunology
Abstract

International audience; Remissions of haematological malignancies have been reported after allo-SCT, despite donor cell rejection, suggesting that sustained allogeneic engraftment is not mandatory to obtain a lasting anti-tumour effect. To evaluate the potential benefit from transient post-allo-SCT alloreactivity, we took advantage of the Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC) registry to colligate 14 patients with an efficient and long-lasting allogeneic (GVL) effect after allo-SCT for haematological malignancies, despite transient or absent engraftment. None received a second allogeneic graft after autologous recovery. The median duration of remission after autologous reconstitution was 118 (12-252) months. Although we cannot exclude the possibility that some patients were cured before allo-SCT, this retrospective analysis does strongly suggest that an efficient GVL effect can be observed without sustained donor engraftment, and that the transient presence of donor T cells might be sufficient to induce a powerful GVL effect.

Published
2009
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30. Influence of mannose-binding lectin genotypes and serostatus in allo-SCT: analysis of 131 recipients and donors

Author

Tatjana Zabelina, R Thiébaut, Ulrike Bacher, N. Kroeger, Hartmut Kabisch, R M Haston, Boris Fehse, Michael Lioznov, F Ayuk, Axel R. Zander, P Das, Nigel Klein, Olaf Neth, Olga Waschke, Mouillet, Evelyne, Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Department of Paediatric Infectious Diseases and Immunology, Hospital Universitario Virgen del Roci, Department of Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), Department of Pediatric Hematology and Oncology, University of Hamburg, Department of Experimental Pediatric Oncology and Hematology, University Hospital of the Johann Wolfgang Goethe-University, Epidémiologie et Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2, and Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Tissue Donors, Graft vs Host Disease, MESH: Genotype, 0302 clinical medicine, Genotype, Prospective Studies, MESH: Sepsis, Mannan-binding lectin, MESH: Aged, 0303 health sciences, Hematology, MESH: Middle Aged, Middle Aged, Tissue Donors, 3. Good health, MESH: Mannose-Binding Lectin, Phenotype, Female, Disease Susceptibility, MESH: Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, MESH: Disease Susceptibility, MESH: Graft vs Host Disease, chemical and pharmacologic phenomena, Biology, MESH: Phenotype, Mannose-Binding Lectin, Article, Sepsis, 03 medical and health sciences, MESH: Mycoses, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, 030304 developmental biology, Aged, Retrospective Studies, MESH: Adolescent, Transplantation, MESH: Humans, Lectin, MESH: Adult, MESH: Retrospective Studies, Fungal pneumonia, medicine.disease, bacterial infections and mycoses, MESH: Prospective Studies, MESH: Male, Complement system, Mycoses, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, 030215 immunology, Stem Cell Transplantation
Abstract

International audience; Mannan-binding lectin (MBL) deficiency is determined by MBL gene polymorphisms and is associated with an increased infection risk. To clarify the role of MBL in Allo-SCT, 131 recipients-donors were analysed. MBL genotypes were determined by PCR and heteroduplex analyses, MBL serum levels by ELISA, and MBL oligomers by western blotting. MBL levels

Published
2009
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31. FTY720 Inhibits Tumor Necrosis Factor-α-Induced Proliferation and Extracellular Signal-Regulated Kinase Phosphorylation of Human Smooth Muscle Cells

Author

Nathalie Augé, Lionel Rostaing, Mogens Thomsen, Lucie Etienne, Cindy Canivet, Robert Salvayre, Tomsen Böhler, Sylvain Galvani, Anne Nègre-Salvayre, Nassim Kamar, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie, dialyse et transplantation [Hôpital de Rangueil, Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Simon, Marie Francoise, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Graft Rejection, MESH: Signal Transduction, MAPK/ERK pathway, [SDV]Life Sciences [q-bio], MESH: Muscle, Smooth, 0302 clinical medicine, Sphingosine, hemic and lymphatic diseases, Myocyte, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, MESH: Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Kinase, 3. Good health, MESH: Cell Survival, 030220 oncology & carcinogenesis, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, MESH: Immunosuppressive Agents, MESH: Sphingosine, Signal transduction, Cell Division, Immunosuppressive Agents, Signal Transduction, MESH: Cells, Cultured, Cell Survival, MESH: Graft Rejection, Biology, 03 medical and health sciences, MESH: Transplantation, Homologous, Extracellular, Humans, Transplantation, Homologous, MESH: Propylene Glycols, 030304 developmental biology, Transplantation, MESH: Humans, MESH: Phosphorylation, Fingolimod Hydrochloride, Tumor Necrosis Factor-alpha, Cell growth, Muscle, Smooth, Propylene Glycols, MESH: Tumor Necrosis Factor-alpha, Cancer research, Surgery
Abstract

International audience; We investigated the effects of the sphingolipid FTY720 on tumor necrosis factor-alpha (TNF-alpha)-induced proliferation and signal transduction in human smooth muscle cells (SMC). We showed that clinically relevant concentrations of FTY720 inhibited TNF-alpha-induced SMC proliferation and extracellular signal-regulated kinase (ERK) phosphorylation. We concluded that FTY720 may be a useful drug to inhibit chronic vascular rejection.

Published
2009
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32. Diagnosis of toxoplasmosis after allogeneic stem cell transplantation: results of DNA detection and serological techniques

Author

Frédéric Garban, Marie-Pierre Brenier-Pinchart, Jean-Paul Brion, Hervé Pelloux, Rebecca Hamidfar, Jean-Yves Cahn, Jean-François Timsit, Claude-Eric Bulabois, Hélène Fricker-Hidalgo, Laboratoire de parasitologie-mycologie, CHU Grenoble, Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Maladie Infectieuse, and Vesin, Aurélien

Subjects
Male, medicine.medical_treatment, Antibodies, Protozoan, Hematopoietic stem cell transplantation, Polymerase Chain Reaction, Immunoglobulin G, Serology, law.invention, 0302 clinical medicine, law, MESH: Animals, 030212 general & internal medicine, Polymerase chain reaction, MESH: Immunoglobulin G, 0303 health sciences, MESH: Middle Aged, biology, MESH: Toxoplasma, MESH: Enzyme-Linked Immunosorbent Assay, Middle Aged, MESH: Immunoglobulin M, 3. Good health, Infectious Diseases, MESH: Toxoplasmosis, Female, MESH: Stem Cell Transplantation, Toxoplasma, Toxoplasmosis, Microbiology (medical), MESH: DNA, Protozoan, Enzyme-Linked Immunosorbent Assay, 03 medical and health sciences, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH: Antibodies, Protozoan, MESH: Humans, 030306 microbiology, business.industry, Toxoplasma gondii, MESH: Polymerase Chain Reaction, DNA, Protozoan, medicine.disease, biology.organism_classification, Virology, MESH: Male, Transplantation, Immunoglobulin M, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Stem Cell Transplantation
Abstract

International audience; BACKGROUND: The biological diagnosis of toxoplasmosis after allogeneic hematopoietic stem cell transplantation (HSCT) is based on the detection of Toxoplasma gondii DNA in blood specimens or other samples. Serological testing is used mainly to define the immunity status of the patient before HSCT. The aim of our study was to examine the performance of polymerase chain reaction (PCR) and serological techniques in the diagnosis of toxoplasmosis after HSCT. METHODS: Seventy patients underwent allogeneic HSCT from September 2004 through September 2006. DNA was detected by PCR, and immunoglobulin G and immunoglobulin M were detected by enzyme-linked immunosorbent assay. RESULTS: The results of immunoglobulin G detection before allogeneic HSCT were positive in 40 (57.1%) of the patients and negative in 30 (42.9%). After HSCT, 57 patients (81.4%) had test results that were negative for immunoglobulin M and had negative results of DNA detection, without toxoplasmosis infection. Four patients (5.7%) had at least 4 samples with positive PCR results and/or test results positive for immunoglobulin M against T. gondii; toxoplasmosis was then confirmed by clinical symptoms. Nine patients (12.9%) with positive PCR results and 1 or 2 samples with test results negative for immunoglobulin M were considered to have asymptomatic T. gondii infection. Reactivation of latent infection was the cause of toxoplasmosis in 3 of the 4 patients, and toxoplasmosis occurred as a primary infection in 1 patient. The detection of specific anti-T. gondii immunoglobulin M was the only biological evidence of toxoplasmosis in 2 patients, and samples were positive for immunoglobulin M before PCR was performed in 1 patient. CONCLUSIONS: Thus, after HSCT, all patients were at risk for toxoplasmosis; all patients who receive HSCTs should be followed up with biological testing that combines PCR and serological techniques.

Published
2009
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33. Bone scintigraphy pattern of joint chronic graft-versus-host disease after allogeneic bone marrow transplantation

Author

Oleg Blagosklonov, Ingrid Biancheri, Frédéric Paycha, Michel Runge, C.-M. Ungureanu, Daniel Wendling, Hatem Boulahdour, O. Angoue, Réka Zsigmond, Fabrice Larosa, WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine nucléaire, biophysique, isotopes [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Agents pathogènes et inflammation - UFC (EA 4266) (API)

Subjects
Adult, Male, medicine.medical_specialty, Graft vs Host Disease, MESH: Graft vs Host Disease, Bone and Bones, 03 medical and health sciences, 0302 clinical medicine, Text mining, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Radiology, Nuclear Medicine and imaging, Autogenous bone, Radionuclide Imaging, MESH: Bone Marrow Transplantation, ComputingMilieux_MISCELLANEOUS, Bone Marrow Transplantation, MESH: Humans, medicine.diagnostic_test, business.industry, Marrow transplantation, MESH: Chronic Disease, MESH: Adult, General Medicine, MESH: Bone and Bones, medicine.disease, MESH: Male, 3. Good health, Surgery, MESH: Joints, Graft-versus-host disease, Bone scintigraphy, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Chronic Disease, Joints, business, 030215 immunology
Abstract

International audience

Published
2009
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34. Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation

Author

Jean Soulier, Philippe Bertheau, Mariana Varna, Hideyuki Murata, Christophe Leboeuf, Philippe Ratajczak, Eliane Gluckman, Jean-Michel Cayuela, Allison Desveaux, Luc Legrès, Anne Janin, Gérard Socié, Ratajczak, Philippe, Service d'anatomo-pathologie [Paris], 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), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire central d'hématologie, Service de greffe de moelle osseuse [Saint-Louis], Pathologie et virologie moléculaire (PVM (UMR_7151)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Pathology, MESH: Tissue Donors, Graft vs Host Disease, Transplantation Chimera, Biochemistry, MESH: Mouth Neoplasms, 0302 clinical medicine, Medicine, MESH: In Situ Hybridization, Fluorescence, MESH: Bone Marrow Transplantation, In Situ Hybridization, Fluorescence, Bone Marrow Transplantation, 0303 health sciences, MESH: Carcinoma, Squamous Cell, Hematology, Tissue Donors, 3. Good health, Haematopoiesis, medicine.anatomical_structure, MESH: Young Adult, Child, Preschool, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Mouth Neoplasms, Stem cell, MESH: Transplantation Chimera, Adult, medicine.medical_specialty, Allogeneic transplantation, Immunology, MESH: Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Young Adult, 03 medical and health sciences, Sex Factors, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Sex Factors, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, 030304 developmental biology, MESH: Humans, business.industry, Mesenchymal stem cell, MESH: Child, Preschool, MESH: Adult, Cell Biology, medicine.disease, MESH: Male, Transplantation, Graft-versus-host disease, Bone marrow, business, MESH: Female
Abstract

In animal models, tissue stem cells were proposed to exhibit an unexpected level of plasticity, although issues on cell fusions have lead to some controversies. Only transplantation experiments using genetically distinct recipients and donors can unequivocally show these changes in cell fate. We have analyzed oral squamous cell carcinomas arising in 8 long-term survivors of allogeneic bone marrow transplantation, in whom chronic graft-versus-host disease greatly favors development of squamous cell carcinomas, possibly as a consequence of lichenoid mucosal inflammation. With the use of 2 independent methods, (1) combined immunostaining and fluorescent in situ hybridization (FISH) analysis for X and Y chromosomes sequences in sex-mismatched grafts and (2) comparison of microsatellite typing of laser-microdissected tumor, donor, and recipient cells, in all tumors, we showed that 4 of these 8 epithelial tumors actually arose from the engrafted allogeneic bone marrow. Thus, donor-derived bone marrow cells, whether hematopoietic or mesenchymal, recruited to sites of chronic mucosal inflammation yielded epithelial tumors. Our observations therefore show that marrow cells in humans have a major role in epithelial cancer formation after allogeneic transplantation.

Published
2009
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35. Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation

Author

Agnès Devergie, Tapani Ruutu, Argiris Symeonidis, Judith Dierlamm, Ronald Brand, Dietrich W. Beelen, Theo de Witte, Alois Gratwohl, Jackie Cornish, Axel R. Zander, Anja van Biezen, Dietger Niederwieser, Catherine Cordonnier, Nicolaus Kröger, Per Ljungman, Eric Deconinck, Marrow Transplantation, Saas, Philippe, Dept. for Stem Cell Transplantation, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Dept. of Medical Statistics, Universiteit Leiden [Leiden], Dept. of Haematology and Oncology, University Hospital, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dept. of Medicine, Helsinki University Central Hospital, Dept. of Paediatric Oncology/BMT, Bristol Royal Hospital for Children, Dept. of Hematology, University hospitals, 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), Dept. of Bone Marrow Transplantation, University Hospital, Essen, Service greffe de moelle osseuse, and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Myeloid, medicine.medical_treatment, Hematopoietic stem cell transplantation, Gastroenterology, cytogenetic abnormalities, 0302 clinical medicine, Immune Regulation [NCMLS 2], allogeneic stem cell transplantation, MESH: Risk Factors, MESH: Child, Cumulative incidence, MESH: Treatment Outcome, MESH: Aged, Hematology, MESH: Middle Aged, Myeloid leukemia, 3. Good health, medicine.anatomical_structure, MESH: Young Adult, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Leukemia, Myeloid, Acute, MESH: Myelodysplastic Syndromes, medicine.medical_specialty, MESH: Neoplasms, Second Primary, [SDV.IMM] Life Sciences [q-bio]/Immunology, acute myelogenous leukemia, MESH: Prognosis, 03 medical and health sciences, Translational research [ONCOL 3], Internal medicine, medicine, MESH: Transplantation, Homologous, Risk factor, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Humans, business.industry, Myelodysplastic syndromes, MESH: Child, Preschool, therapy-related, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Surgery, myelodysplastic syndrome, Transplantation, business, 030215 immunology
Abstract

Contains fulltext : 81636.pdf (Publisher’s version ) (Open Access) BACKGROUND: After successful treatment of malignant diseases, therapy-related myelodysplastic syndrome and acute myeloid leukemia have emerged as significant problems. DESIGN AND METHODS: The aim of this study was to investigate outcome and risk factors in patients with therapy-related myelodysplastic syndrome or acute myeloid leukemia who underwent allogeneic stem cell transplantation. Between 1981 and 2006, 461 patients with therapy-related myelodysplastic syndrome or acute myeloid, a median age of 40 years and a history of solid tumor (n=163), malignant lymphoma (n=133), or other hematologic diseases (n=57) underwent stem cell transplantation and their data were reported to the European Group for Blood and Marrow Transplantation. RESULTS: The cumulative incidence of non-relapse mortality and relapse at 3 years was 37% and 31%, respectively. In a multivariate analysis significant factors for relapse were not being in complete remission at the time of transplantation (p=0.002), abnormal cytogenetics (p=0.005), higher patients' age (p=0.03) and therapy-related myelodysplastic syndrome (p=0.04), while higher non-relapse mortality was influenced by higher patients' age. Furthermore, there was a marked reduction in non-relapse mortality per calendar year during the study period (p

Published
2009
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36. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma

Author

Moreau, Philippe, Garban, Frédéric, Attal, Michel, Michallet, Mauricette, Marit, Gérald, Hulin, Cyrille, Benboubker, Lotfi, Doyen, Chantal, Mohty, Mohamad, Yakoub-Agha, Ibrahim, Leyvraz, Serge, Casassus, Philippe, Avet-Loiseau, Hervé, Garderet, Laurent, Mathiot, Claire, Harousseau, Jean-Luc, Renseigné, Non, Hématologie et oncologie pédiatrique, Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, 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], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier ( UPS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
medicine.medical_specialty, MESH : Transplantation, Autologous, MESH : Transplantation, Homologous, Long term follow up, MESH : Transplantation Conditioning, medicine.medical_treatment, Immunology, MESH: Multiple Myeloma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, MESH : Stem Cell Transplantation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Conditioning regimen, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, MESH: Risk Factors, hemic and lymphatic diseases, medicine, MESH: Transplantation, Homologous, Autologous transplantation, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, MESH: Transplantation Conditioning, MESH: Humans, business.industry, MESH : Humans, MESH : Follow-Up Studies, Cell Biology, Hematology, MESH: Follow-Up Studies, medicine.disease, MESH : Risk Factors, MESH: Transplantation, Autologous, 3. Good health, Surgery, Fludarabine, 030220 oncology & carcinogenesis, MESH: Disease-Free Survival, MESH : Disease-Free Survival, MESH: Stem Cell Transplantation, MESH : Multiple Myeloma, business, Busulfan, 030215 immunology, medicine.drug, Allotransplantation
Abstract

To the editor: Recent pilot studies combining a cytoreductive autologous stem cell transplantation (ASCT) with a reduced-intensity conditioning regimen (RIC) allograft have reported encouraging results in patients with de novo multiple myeloma (MM).[1][1],[2][2] However, it remains to be determined

Published
2008
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37. Cryptosporidiosis in paediatric renal transplantation

Author

Sophie Cassaing, Alexis Valentin, Marie-Denise Linas, Arnaud Garnier, Agnes Carol, Véronique Baudouin, Flavio Bandin, Vincent Guigonis, Theresa Kwon, Stéphane Decramer, Service de néphrologie pédiatrique, Centre de Référence du Sud Ouest des Maladies Rénales Rares-Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], 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), faculte des sciences pharmaceutiques (umr 152 IRD), Faculte des Sciences Pharmaceutiques, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Nephrology, Male, Time Factors, medicine.medical_treatment, Biopsy, 030232 urology & nephrology, Cryptosporidiosis, Kidney, MESH: Kidney Transplantation, Cohort Studies, MESH: Biopsy, 0302 clinical medicine, MESH: Child, 030212 general & internal medicine, Child, MESH: Cohort Studies, MESH: Antiparasitic Agents, MESH: Treatment Outcome, biology, Antiparasitic Agents, Incidence (epidemiology), digestive, oral, and skin physiology, Cryptosporidium, Immunosuppression, Nitazoxanide, MESH: Follow-Up Studies, Nitro Compounds, 3. Good health, MESH: Diarrhea, Treatment Outcome, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Diarrhea, medicine.medical_specialty, Adolescent, MESH: Thiazoles, MESH: Drug Administration Schedule, Mycophenolic acid, Drug Administration Schedule, Tacrolimus, 03 medical and health sciences, Internal medicine, medicine, MESH: Tacrolimus, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Mycophenolic Acid, MESH: Adolescent, Sirolimus, MESH: Humans, business.industry, MESH: Time Factors, MESH: Cryptosporidiosis, MESH: Kidney, Mycophenolic Acid, biology.organism_classification, Kidney Transplantation, MESH: Male, Surgery, Transplantation, Thiazoles, Pediatrics, Perinatology and Child Health, Prednisone, MESH: Sirolimus, business, MESH: Prednisone, MESH: Female, Follow-Up Studies
Abstract

International audience; Diarrhoea in transplantation may be secondary to infectious agents and immunosuppressive drugs. The use of combined immunosuppressive drugs increases the incidence of infectious diarrhoea. We retrospectively collected all diarrhoea episodes during a 3-year period in 199 pediatric renal transplant recipients, including 47 patients receiving a kidney transplant during this period. We diagnosed 64 diarrhoea episodes (32% of the patients, 10.7% per year). Fourteen diarrhoea episodes could be attributed to the immunosuppressive treatment, and 12 remained without diagnosis. Nineteen patients (

Published
2008
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38. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity

Author

Céline Cognet, Rita Maccario, Maria Ester Bernardo, Daniela Pende, Michela Falco, Maria Cristina Mingari, Franco Locatelli, Miryam Martinetti, Elisa Romeo, Stefania Martini, Lorenzo Moretta, Stefania Marcenaro, Daniela Montagna, Eric Vivier, Alessandro Moretta, Istituto Nazionale per la Ricerca sul Cancro, Genova, Immunologia, Università di Genova, Dipartimento di Medicina Sperimentale, Istituto Giannina Gaslini, Genova, Immunologia Clinica e Sperimentale, Università degli Studi di Pavia, Centre d'Immunologie de Marseille - Luminy (CIML), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Pavia = University of Pavia (UNIPV), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pende, D, Marcenaro, S, Falco, M, Martini, S, Bernardo, M, Montagna, D, Romeo, E, Cognet, C, Martinetti, M, Maccario, R, Mingari, Mc, Vivier, E, Moretta, L, Locatelli, F, and Moretta, A

Subjects
Male, MESH: Tissue Donors, medicine.medical_treatment, KIR Ligand, Hematopoietic stem cell transplantation, Biochemistry, Substrate Specificity, Interleukin 21, 0302 clinical medicine, Receptors, KIR, hemic and lymphatic diseases, MESH: Child, Child, Cells, Cultured, 0303 health sciences, Leukemia, biology, Histocompatibility Testing, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Transplantation, Tissue Donors, 3. Good health, Killer Cells, Natural, MESH: Young Adult, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, MESH: Cells, Cultured, MESH: Killer Cells, Natural, Adolescent, Immunology, Graft vs Leukemia Effect, Human leukocyte antigen, MESH: Histocompatibility Testing, 03 medical and health sciences, Young Adult, KIR2DL1, MESH: Receptors, KIR, MESH: Leukemia, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Patient Selection, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, MESH: Adolescent, Transplantation, MESH: Humans, Patient Selection, MESH: Child, Preschool, Cell Biology, MESH: Graft vs Leukemia Effect, medicine.disease, MESH: Male, biology.protein, MESH: Substrate Specificity, MESH: Female, 030215 immunology
Abstract

We analyzed 21 children with leukemia receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from killer immunoglobulin (Ig)–like receptors (KIR) ligand-mismatched donors. We showed that, in most transplantation patients, variable proportions of donor-derived alloreactive natural killer (NK) cells displaying anti-leukemia activity were generated and maintained even late after transplantation. This was assessed through analysis of donor KIR genotype, as well as through phenotypic and functional analyses of NK cells, both at the polyclonal and clonal level. Donor-derived KIR2DL1+ NK cells isolated from the recipient displayed the expected capability of selectively killing C1/C1 target cells, including patient leukemia blasts. Differently, KIR2DL2/3+ NK cells displayed poor alloreactivity against leukemia cells carrying human leukocyte antigen (HLA) alleles belonging to C2 group. Unexpectedly, this was due to recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, C2/C2 leukemia blasts were killed by KIR2DL2/3+ (or by NKG2A+) NK cells that coexpressed KIR2DS1. This could be explained by the ability of KIR2DS1 to directly recognize C2 on leukemia cells. A role of the KIR2DS2 activating receptor in leukemia cell lysis could not be demonstrated. Altogether, these results may have important clinical implications for the selection of optimal donors for haplo-HSCT.

Published
2008
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39. Successful retransplantation of a kidney allograft affected by thrombotic microangiopathy into a second transplant recipient

Author

Céline Guilbeau-Frugier, Didier Noury, Marylise Fort, Lionel Rostaing, Marie-Bernadette Delisle, Nassim Kamar, Federico Sallusto, Pascal Rischmann, Mehdi Khedis, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie - Transplantation Rénale - Andrologie, Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, Laboratoire d'Immunologie et d'Histocompatibilité, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Urologie-Andrologie et Transplantation Rénale [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département Immunologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Simon, Marie Francoise

Subjects
Adult, Nephrology, medicine.medical_specialty, MESH: Tissue Donors, Tissue and Organ Procurement, Thrombotic microangiopathy, Biopsy, medicine.medical_treatment, 030232 urology & nephrology, Renal function, 030230 surgery, Kidney, MESH: Tissue and Organ Procurement, Nephrectomy, MESH: Kidney Transplantation, 03 medical and health sciences, MESH: Biopsy, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Polycystic kidney disease, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Thrombosis, Kidney transplantation, MESH: Humans, MESH: Middle Aged, business.industry, Thrombosis, MESH: Adult, MESH: Kidney, Middle Aged, medicine.disease, Kidney Transplantation, Tissue Donors, 3. Good health, Surgery, MESH: Recurrence, Transplantation, MESH: Nephrectomy, surgical procedures, operative, Female, business, MESH: Female, Kidney disease
Abstract

International audience; The donor organ shortage has compelled transplant centers to use organs from nontraditional sources. One example is the reuse of a previously transplanted organ, such as a kidney or liver retrieved from a brain-dead allograft recipient. For the first time, we reused a previously transplanted kidney that experienced intractable recurrent thrombotic microangiopathy (TMA) from a living allograft recipient. Within a few weeks posttransplantation, a deceased kidney allograft recipient developed intractable severe recurrent idiopathic TMA in the allograft despite intensive plasma exchanges and steroid and rituximab therapy. This required nephrectomy to cure TMA. The index recipient was believed to have a well-functioning allograft despite TMA (serum creatinine, 1.36 mg/dL [120 micromol/L]) and microalbuminuria with albumin of 1.2 g/dL [12 g/L]), and it appeared mildly damaged on biopsy examination. After donor and recipient informed consents were obtained and after approval of the French Agency of Biomedicine, the TMA allograft was reused and transplanted into a recipient whose original kidney disease was polycystic kidney disease. The retransplantation was uneventful, and at 6 months posttransplantation, the ultimate recipient's serum creatinine level was 1.06 mg/L (97 micromol/L) and albuminuria was 0.5 g/dL (5 g/L). A routine kidney biopsy showed mild glomerular lesions. After allograft nephrectomy, the donor's hematologic TMA symptoms dissipated within 10 days. We conclude that a kidney allograft with TMA recurrence can be successfully retransplanted into another recipient with excellent kidney function while still curing the first recipient of recurrent TMA. This might increase the number of kidney allografts from extended criteria donors.

Published
2008
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40. [Towards the use of intravenous apoptotic leukocyte infusion as a cell-based therapy approach?]

Author

Saas, Philippe, Bonnefoy, Francis, Kleinclauss, Francois, Sun, Yunwei, Tiberghien, Pierre, Gaugler, Béatrice, Perruche, Sylvain, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Graft vs Host Disease, MESH: Graft vs Host Disease, Apoptosis, MESH: Blood Transfusion, MESH: Leukocytes, Leukocytes, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Blood Transfusion, Infusions, Intravenous, MESH: Bone Marrow Transplantation, MESH: Infusions, Intravenous, MESH: Hematopoietic Stem Cell Transplantation, Bone Marrow Transplantation, Immunosuppression Therapy, MESH: Cytokines, MESH: Humans, MESH: Apoptosis, Hematopoietic Stem Cell Transplantation, MESH: Immunosuppression, MESH: Leukocyte Transfusion, Leukocyte Transfusion, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience; In the past few years, significant advances have been performed in the field of cell-based therapies. This concerns mainly regenerative medicine with the use of stem cells, as well as the modulation of immune responses. In order to modulate allogeneic immune responses after transplantation, we have developed a cell therapy approach based on the immunomodulatory properties of intravenous donor apoptotic cell infusion. In allogeneic hematopoietic cell transplantation settings, we reported that intravenous apoptotic leukocyte infusion, simultaneously to allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents alloimmunization and delays graft-versus-host disease. Here, we review the different factors and cells implicated in the immunomodulatory properties of apoptotic cells. Then, we discuss the potential significance of such observations in transfusion practice.

Published
2008
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41. Inflammatory cytokines and dendritic cells in acute graft-versus-host disease after allogeneic stem cell transplantation

Author

Béatrice Gaugler, Mohamad Mohty, Recherches en cancérologie, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Endocrinology, Diabetes and Metabolism, T-Lymphocytes, Immunology, Graft vs Host Disease, MESH: Graft vs Host Disease, Context (language use), chemical and pharmacologic phenomena, Biology, General Biochemistry, Genetics and Molecular Biology, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immune system, immune system diseases, MESH: Transplantation, Homologous, Immunology and Allergy, Animals, Humans, Transplantation, Homologous, MESH: Animals, 030304 developmental biology, 0303 health sciences, MESH: Humans, MESH: Dendritic Cells, Tumor Necrosis Factor-alpha, Interleukin, MESH: Interleukin-1, Dendritic Cells, Transplantation, surgical procedures, operative, MESH: T-Lymphocytes, MESH: Tumor Necrosis Factor-alpha, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, Stem cell, MESH: Stem Cell Transplantation, CD8, 030215 immunology, Interleukin-1, Stem Cell Transplantation
Abstract

International audience; The wider use of allogeneic stem cell transplantation (allo-SCT) is still limited by the immunologic recognition and destruction of host tissues, termed graft-versus-host disease (GVHD). The role of inflammatory cytokines such as TNF-alpha and IL-1, and their impact on immune effectors (mainly CD4+ and CD8+ T) cells has been extensively studied in the context of GVHD occurring after standard myeloablative allo-SCT. However, recent data suggested that GVHD pathophysiology is likely to involve more complex interactions where antigen-presenting cells, especially dendritic cells (DCs), may play a major role at time of initiation of acute GVHD. In addition, the wider use of reduced intensity and less toxic conditioning (RIC) regimens prior to allo-SCT would allow better visualization of the fine functions of immune effectors, thereby offering a window of opportunities to better decipher the intimate pathophysiological mechanisms underlying GVHD. The aim of this work is to review the available research evidence on the role of DCs as in vivo regulators of alloimmune reactivity, and their interactions with other immune effectors.

Published
2008
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42. Preventive effect of ultraviolet radiation on murine chronic sclerodermatous graft-versus-host disease

Author

Pierre Tiberghien, Jean Sébastien Guerrini, Régis Angonin, Isabelle Mermet, François Kleinclauss, Aliette Marandin, Philippe Saas, François Aubin, Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Saas, Philippe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)

Subjects
MESH: Spleen, Graft vs Host Disease, Mice, 0302 clinical medicine, immune system diseases, MESH: Animals, MESH: Bone Marrow Transplantation, Ultraviolet radiation, Bone Marrow Transplantation, MESH: Langerhans Cells, 0303 health sciences, Mice, Inbred BALB C, integumentary system, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, surgical procedures, operative, Lymphocyte Transfusion, MESH: Lymphocyte Transfusion, [SDV.IMM]Life Sciences [q-bio]/Immunology, Clinical evaluation, [SDV.IMM] Life Sciences [q-bio]/Immunology, Ultraviolet Rays, MESH: Mice, Inbred BALB C, MESH: Graft vs Host Disease, Spleen, Mice, Inbred Strains, chemical and pharmacologic phenomena, MESH: Mice, Inbred Strains, MESH: Scleroderma, Limited, 03 medical and health sciences, Scleroderma, Limited, medicine, MESH: Transplantation, Homologous, Animals, Transplantation, Homologous, Uvb irradiation, MESH: Mice, 030304 developmental biology, Transplantation, business.industry, MESH: Immunohistochemistry, medicine.disease, Disease Models, Animal, Graft-versus-host disease, Murine model, Langerhans Cells, Immunology, MESH: Ultraviolet Rays, Bone marrow, MESH: Disease Models, Animal, business, 030215 immunology
Abstract

International audience; Although previous studies have demonstrated the efficient modulatory effects of ultraviolet radiation B (UVB) on cutaneous graft-versus-host disease (GVHD), most animal research on GVHD has been performed in murine models of acute GVHD. Here, we studied the preventive effect of UVB radiation on the occurrence of chronic sclerodermatous (Scl) GVHD in a murine model. Scl GVHD was induced by transplanting lethally irradiated BALB/c mice with B10.D2 bone marrow and spleen cells. Recipient mice were exposed to UVB before or after bone marrow and spleen cell infusion. Histological and clinical evaluation of GVHD was performed, in association with the characterization of epidermal Langerhans cells. UVB irradiation of recipients after, and more remarkably before, transplantation induced a decrease of Scl GVHD severity associated with epidermal Langerhans cells depletion. We conclude that UVB irradiation of recipient before or after transplantation has a preventive effect on cutaneous Scl GVHD and may represent an effective strategy for prevention of Scl GVHD.

Published
2007
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43. Deletions within the HSV-tk transgene in long-lasting circulating gene-modified T cells infused with a hematopoietic graft

Author

Christophe Ferrand, Pierre Tiberghien, Céline Pagneux, Eric Robinet, Patricia Mercier-Lethondal, Jean-Yves Cahn, Carole Henry, Bruno Lioure, Eric Deconinck, Jean Marie Certoux, Marina Deschamps, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Graft vs Host Disease, MESH: Base Sequence, Biochemistry, Polymerase Chain Reaction, 0302 clinical medicine, Simplexvirus, Lymphocytes, Transgenes, MESH: Bone Marrow Transplantation, Bone Marrow Transplantation, Sequence Deletion, 0303 health sciences, MESH: Middle Aged, Clinical Trials, Phase I as Topic, Hematology, MESH: Follow-Up Studies, Middle Aged, MESH: Sequence Deletion, 3. Good health, Haematopoiesis, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Lymphocyte Transfusion, MESH: Kanamycin Kinase, MESH: Lymphocyte Transfusion, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Clinical Trials, Phase II as Topic, medicine.drug, Ganciclovir, MESH: Thymidine Kinase, [SDV.IMM] Life Sciences [q-bio]/Immunology, Transgene, Immunology, MESH: Graft vs Host Disease, MESH: Transgenes, Biology, Thymidine Kinase, Lymphocyte Depletion, 03 medical and health sciences, Viral Proteins, Immune system, Clinical Trials, Phase II as Topic, In vivo, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Simplexvirus, 030304 developmental biology, MESH: Lymphocyte Depletion, MESH: Humans, Base Sequence, Kanamycin Kinase, MESH: Polymerase Chain Reaction, Cell Biology, Genetic Therapy, medicine.disease, Virology, Molecular biology, MESH: Viral Proteins, MESH: Male, Transplantation, Graft-versus-host disease, MESH: Clinical Trials, Phase I as Topic, Thymidine kinase, MESH: Lymphocytes, MESH: Gene Therapy, MESH: Female, Follow-Up Studies, MESH: Hematologic Neoplasms
Abstract

In our previous phase 1/2 study aimed at controlling graft-versus-host disease, 12 patients received Herpes simplex virus thymidine kinase (HSV-tk+)/neomycin phosphotransferase (NeoR+)–expressing donor gene-modified T cells (GMCs) and underwent an HLA-identical sibling T-cell–depleted bone marrow transplantation (BMT). This study's objective was to follow up, to quantify, and to characterize persistently circulating GMCs more than 10 years after BMT. Circulating GMCs remain detectable in all 4 evaluable patients. However, NeoR- and HSV-tk–polymerase chain reaction (PCR) differently quantified in vivo counts, suggesting deletions within the HSV-tk gene. Further experiments, including a novel “transgene walking” PCR method, confirmed the presence of deletions. The deletions were unique, patient-specific, present in most circulating GMCs expressing NeoR, and shown to occur at time of GMC production. Unique patient-specific retroviral insertion sites (ISs) were found in all GMCs capable of in vitro expansion/cloning as well. These findings suggest a rare initial gene deletion event and an in vivo survival advantage of rare GMC clones resulting from an anti–HSV-tk immune response and/or ganciclovir treatment. In conclusion, we show that donor mature T cells infused with a T-cell–depleted graft persist in vivo for more than a decade. These cells, containing transgene deletions and subjected to significant in vivo selection, represent a small fraction of T cells infused at transplantation.

Published
2007
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44. Effect of the shipment of cadaveric renal allografts on allograft survival

Author

Bruno Moulin, Francis Guillemin, Mourad Hachicha, Jean-Marc Virion, Olivier Toupance, Michèle Kessler, Jean-Michel Rebibou, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CIC - Strasbourg, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Transplantation, CHU Strasbourg, Université de Reims Champagne-Ardenne (URCA), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Saas, Philippe, Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Graft Rejection, Male, medicine.medical_treatment, 030232 urology & nephrology, Transportation, Kaplan-Meier Estimate, 030230 surgery, MESH: Kidney Transplantation, MESH: Proportional Hazards Models, MESH: Delayed Graft Function, 0302 clinical medicine, MESH: Kaplan-Meiers Estimate, MESH: Aged, Kidney, MESH: Middle Aged, Graft Survival, Middle Aged, medicine.anatomical_structure, surgical procedures, operative, Nephrology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Hemodialysis, France, Adult, medicine.medical_specialty, Tissue and Organ Procurement, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Graft Survival, Delayed Graft Function, MESH: Graft Rejection, MESH: Tissue and Organ Procurement, MESH: Multivariate Analysis, 03 medical and health sciences, medicine, MESH: Transplantation, Homologous, Cadaver, MESH: Cadaver, Humans, Transplantation, Homologous, Dialysis, Aged, Proportional Hazards Models, Retrospective Studies, Transplantation, MESH: Humans, business.industry, Proportional hazards model, MESH: Transportation, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, MESH: Male, Surgery, MESH: France, Multivariate Analysis, business, Cadaveric spasm, MESH: Female, Kidney disease
Abstract

International audience; BACKGROUND: Since 1996, the allocation of grafts in France has been based on a hierarchical three-level system: national, regional and local. The objective of this study was to determine whether the shipment of cadaveric kidneys according to these new exchange rules affects allograft outcome in the Eastern region of France. METHODS: This retrospective study analysed all renal transplants performed in the four centres of the French Eastern region during 3 years (1996 to 1998). All patients were followed up until death, return to dialysis, last information date or the end of June 2003. Information regarding the donors, recipients and treatments, as well as patient and graft outcome, was recorded. Factors associated with graft loss were analysed using Cox proportional hazard methods. RESULTS: 542 transplants were analysed, 287 (53%) kidneys were transplanted locally, 229 (42.2%) kidneys coming from exchanges within the region and 26 (4.8%) from another region. There were statistically significant differences between the four centres for donors' and recipient' characteristics and for immunosuppressive treatment, but there was no difference between centres regarding patient survival (94.4% at 5 years), graft survival (83.7% at 5 years) or death-censored graft survival (87.8% at 5 years). Compared to locally transplanted grafts, shipped grafts had significantly better human leukocyte antigen (HLA) matching (2.5 +/- 1.3 versus 2.1 +/- 1.0 matches, P = 0.0005 but a longer cold ischaemia time (23.2 +/- 7.9 versus 19.2 +/- 7.8 h, P < 0.0001). Three independent factors were associated with a reduced graft survival: at least one acute rejection, delayed graft function and a shipped graft. CONCLUSION: The results of this study suggest that the shipment of cadaveric renal allografts in a regional distribution system is associated with better HLA matching but is a significant predictor of graft loss at 5 years. It would be advisable to restrict graft sharing to patients whose access to transplantation is limited, taking special care to avoid any additional factors having a detrimental effect on the outcome.

Published
2007
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45. Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Author

Zina Chir, Noel Milpied, Mauricette Michallet, Marc Renaud, Jean-Michel Boiron, Bernard Rio, Ibrahim Yakoub-Agha, Eric Deconinck, Quoc-Hung Le, Didier Blaise, Franck E. Nicolini, Bruno Lioure, Michel Attal, Helene Esperou, Thomas Prebet, Jean-Henri Bourhis, Mohamad Mohty, Pierre Bordigoni, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Agence de la biomédecine [Saint-Denis la Plaine], 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], Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Hématologie et Oncologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Saas, Philippe

Subjects
Oncology, Male, MESH: Remission Induction, Cancer Research, Multivariate analysis, Transplantation Conditioning, MESH: Registries, MESH: Busulfan, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, 0302 clinical medicine, MESH: Antilymphocyte Serum, MESH: Risk Factors, Risk Factors, MESH: Child, Medicine, Registries, Child, MESH: Transplantation Conditioning, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, MESH: Time, Remission Induction, Hematopoietic Stem Cell Transplantation, MESH: Follow-Up Studies, Hematology, Total body irradiation, Middle Aged, MESH: Infant, MESH: Predictive Value of Tests, 3. Good health, Fludarabine, Treatment Outcome, MESH: Survival Analysis, 030220 oncology & carcinogenesis, Reduced Intensity Conditioning, Child, Preschool, Hematologic Neoplasms, MESH: Vidarabine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Vidarabine, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH: Graft vs Host Disease, MESH: Multivariate Analysis, Disease-Free Survival, Time, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, MESH: Transplantation, Homologous, Genetics, Humans, Transplantation, Homologous, Molecular Biology, Busulfan, MESH: Hematopoietic Stem Cell Transplantation, Aged, Antilymphocyte Serum, Retrospective Studies, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, Cell Biology, Survival Analysis, MESH: Male, Surgery, MESH: France, Transplantation, MESH: Disease-Free Survival, Multivariate Analysis, business, MESH: Female, MESH: Hematologic Neoplasms, 030215 immunology, Follow-Up Studies
Abstract

International audience; This retrospective study analyzed the impact of demographic and transplantation variables on outcomes of 1108 patients who have undergone allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning (RIC HSCT) for hematological malignancies and were reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between November 1994 and December 2004. Only 442 patients (40%) were in complete remission (CR) at time of transplantation. Peripheral blood stem cells were used in the majority of patients (n = 878; 79%), 255 patients received fludarabine and low-dose total body irradiation, while 465 patients (42%) fludarabine and busulfan with rabbit anti-thymocyte globulins (ATG). The impact of demographic and transplant variables was studied on overall (OS) and event-free survival (EFS) in univariate and multivariate analysis. With a median follow-up of 21 months, 3-year probability of OS and EFS was 42% and 30%, respectively, and treatment-related mortality was 15% at 2 years. The multivariate analysis showed a significant negative impact on OS and EFS of the absence of CR status before transplantation; conditioning regimen, including >10 mg/kg ATG; and minor ABO incompatibility. In conclusion, this study highlights the major impact on RIC HSCT outcome of disease status before transplantation, ATG dose and ABO incompatibility.

Published
2007
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46. Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC)

Author

Patrice Chevalier, Reza Tabrizi, Hervé Tilly, Bruno Lioure, Eric Deconinck, Gérard Socié, Jill-Patrice Cassuto, Lionel Ades, Didier Blaise, Mauricette Michallet, Mathieu Kuentz, Michel Attal, Pierre Bordigoni, Thierry Facon, Frédéric Garban, Jean-Paul Vernant, Stéphane Vigouroux, Noel Milpied, Marc Bernard, Norbert Ifrah, Jean-Henri Bourhis, Marc Renaud, Raphaël Porcher, Centre Hospitalier Universitaire [Rennes], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Saas, Philippe, 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), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)

Subjects
Male, Oncology, MESH: Remission Induction, Transplantation Conditioning, MESH: Busulfan, medicine.medical_treatment, Graft vs Host Disease, MESH: Antibodies, Monoclonal, 0302 clinical medicine, MESH: Antilymphocyte Serum, Antineoplastic Combined Chemotherapy Protocols, Melphalan, Etoposide, MESH: Etoposide, MESH: Transplantation Conditioning, MESH: Treatment Outcome, Hematology, MESH: Middle Aged, Remission Induction, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Total body irradiation, 3. Good health, Survival Rate, MESH: Antineoplastic Combined Chemotherapy Protocols, 030220 oncology & carcinogenesis, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Graft vs Leukemia Effect, RIC allogeneic transplantation, Disease-Free Survival, 03 medical and health sciences, MESH: Melphalan, Humans, Cyclophosphamide, Aged, Antilymphocyte Serum, Retrospective Studies, MESH: Humans, MESH: Cyclophosphamide, MESH: Adult, MESH: Retrospective Studies, Survival Analysis, Regimen, MESH: Disease-Free Survival, MESH: Female, Busulfan, MESH: Combined Modality Therapy, T-Lymphocytes, MESH: Carmustine, Kaplan-Meier Estimate, MESH: Proportional Hazards Models, MESH: Lymphoma, Non-Hodgkin, hemic and lymphatic diseases, MESH: Cytarabine, MESH: Data Collection, MESH: Kaplan-Meiers Estimate, MESH: Aged, Data Collection, Lymphoma, Non-Hodgkin, Cytarabine, Middle Aged, Combined Modality Therapy, Fludarabine, MESH: Salvage Therapy, Treatment Outcome, medicine.anatomical_structure, MESH: Survival Analysis, MESH: Vidarabine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, MESH: Whole-Body Irradiation, Vidarabine, Whole-Body Irradiation, medicine.drug, Adult, MESH: Survival Rate, MESH: Graft vs Host Disease, Internal medicine, medicine, MESH: Transplantation, Homologous, Transplantation, Homologous, MESH: Hematopoietic Stem Cell Transplantation, Proportional Hazards Models, Salvage Therapy, Chemotherapy, business.industry, MESH: Graft vs Leukemia Effect, Carmustine, low-grade lymphoma, MESH: Male, Surgery, Transplantation, MESH: France, MESH: T-Lymphocytes, Bone marrow, business, 030215 immunology
Abstract

International audience; BACKGROUND AND OBJECTIVES: High-dose chemotherapy with allogeneic stem cell transplantation (SCT) has proven to be a successful treatment for low-grade lymphoma (LGL), but is associated with considerable transplant-related mortality (TRM). In an effort to reduce toxic mortality while maintaining the graft-versus-leukemia effect, allogeneic SCT has been combined with a reduced-intensity conditioning (RIC) regimen. The aim of this study was to determine the outcome of patients with LGL treated with RIC allogeneic SCT. DESIGN AND METHODS: This retrospective multicenter study included 73 patients with relapsed or refractory LGL allografted after a RIC regimen between 1998 and 2005 whose data were recorded in a French registry. RESULTS: Patients received a median of three lines of therapy prior to RIC allogeneic SCT. The most widely used conditioning regimens were fludarabine + busulfan + antithymocyte globulin (n=43) and fludarabine + total body irradiation (n=21). Prior to allografting, patients were in complete response (CR; n=21), partial response (PR; n=33) or had chemoresistant disease (n=19). The median follow-up was 37 months (range, 16 to 77 months). In patients in CR, PR and chemoresistant disease, the 3-year overall survival rates were 66%, 64% and 32%, respectively, while the 3-year event-free survival rates were 66%, 52% and 32%, respectively. The 3-year cumulative incidences of TRM were 32%, 28% and 63%, respectively. The incidence of relapse was 9.6%. INTERPRETATION AND CONCLUSIONS: Although associated with significant TRM, RIC allogeneic SCT in advanced chemosensitive disease leads to long-term survival.

Published
2007

47. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study

Author

Vey, N., Thomas, X., Picard, C., Kovascovicz, T., Charin, C., Cayuela, J. M., Dombret, H., Dastugue, N., Huguet, F., Bastard, C., Stamatoulas, A., Giollant, M., Tournilhac, O., Macintyre, E., Buzyn, A., Bories, D., Kuentz, M., Dreyfus, F., Delannoy, A., Raynaud, S., Gratecos, N., Bordessoule, Dominique, De Botton, S., Preudhomme, C., Reman, O., Troussard, X., Pigneux, A., Bilhou, C., Vernant, J. P., Boucheix, C., Gabert, J., Renseigné, Non, Laboratoire de chimie et biochimie des substances naturelles, Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Danone Research, Groupe DANONE, Recherche & Développement, EDF (EDF), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'oncohématologie, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Université de Limoges (UNILIM), 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), Laboratoire d'Hématologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Différenciation hématopoïétique normale et leucémique, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Male, Oncology, Cancer Research, MESH: Chromosomes, Human, Pair 19, medicine.medical_treatment, Translocation, Genetic, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Prospective Studies, E2a pbx1, Prospective cohort study, Acute leukemia, MESH: Middle Aged, Pre-B-Cell Leukemia Transcription Factor 1, Hematopoietic Stem Cell Transplantation, Nuclear Proteins, hemic and immune systems, Hematology, Middle Aged, Burkitt Lymphoma, MESH: Translocation, Genetic, 3. Good health, DNA-Binding Proteins, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Chromosomes, Human, Pair 4, Transcriptional Elongation Factors, Stem cell, Myeloid-Lymphoid Leukemia Protein, Adult, medicine.medical_specialty, MESH: Chromosomes, Human, Pair 4, Adolescent, MESH: Chromosomes, Human, Pair 1, 03 medical and health sciences, Proto-Oncogene Proteins, Internal medicine, Acute lymphocytic leukemia, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, neoplasms, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, Chemotherapy, MESH: Humans, business.industry, Chromosomes, Human, Pair 11, MESH: Adult, Histone-Lysine N-Methyltransferase, B-cell acute lymphoblastic leukemia, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, Transplantation, MESH: Burkitt Lymphoma, MESH: Proto-Oncogene Proteins, MESH: Myeloid-Lymphoid Leukemia Protein, MESH: Chromosomes, Human, Pair 11, business, Chromosomes, Human, Pair 19, MESH: Female, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins, 030215 immunology
Abstract

International audience; Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor.

Published
2006
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48. Impact of cyclosporine reduction with MMF: a randomized trial in chronic allograft dysfunction. The 'reference' study

Author

François Provôt, Claire Pouteil-Noble, Michèle Kessler, Bernard Charpentier, Elisabeth Cassuto-Viguier, Lionel Rostaing, Christian Noel, Didier Ducloux, Bernard Bourbigot, Jean-Daniel Sraer, Sandrine Girardot-Seguin, Denis Glotz, Luc Frimat, Philippe Lang, Bruno Moulin, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de néphrologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, Service de néphrologie et transplantation, 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'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Roche, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Saas, Philippe

Subjects
Male, 030232 urology & nephrology, 030230 surgery, MESH: Cyclosporine, law.invention, MESH: Kidney Transplantation, chemistry.chemical_compound, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, Chronic allograft nephropathy, law, MESH: Postoperative Complications, Immunology and Allergy, Pharmacology (medical), MESH: Treatment Outcome, MESH: Middle Aged, Middle Aged, 3. Good health, Treatment Outcome, Cyclosporine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Safety, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Urology, Renal function, MESH: Drug Administration Schedule, Mycophenolic acid, Drug Administration Schedule, Nephropathy, 03 medical and health sciences, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH: Patient Selection, MESH: Mycophenolic Acid, Transplantation, Creatinine, MESH: Humans, business.industry, Patient Selection, MESH: Safety, MESH: Adult, Mycophenolic Acid, medicine.disease, Kidney Transplantation, MESH: Male, Surgery, chemistry, business, MESH: Female, Kidney disease
Abstract

International audience; Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7-3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 x 10(-4) vs. -3.0 x 10(-4), respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up.

Published
2006
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49. Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipients

Author

Chantal Lagresle-Peyrou, Christophe Hue, Marina Cavazzana-Calvo, Alain Fischer, Allen Liu, Michèle Malassis-Séris, Christian A. J. Vosshenrich, James P. Di Santo, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Développement Lymphoïde, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biothérapie [CHU Necker], 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), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Supported by grants from INSERM, the Institut Pasteur, Ligue National Contre le Cancer, Ministère de la Recherche, and the Contrat Européen Consert 'Concerted Safety and Efficiency Evaluation of Retroviral Transgenesis in Gene Therapy of Inherited Diseases' (contract no. LSHB-CT-2004-005242, coordinator, G. Wagemaker). A.L. received a fellowship from Harvard University., Vosshenrich, Christian, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Transplantation Conditioning, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, Biochemistry, MESH: Hematopoietic Stem Cells, 0302 clinical medicine, b-lymphocytes, MESH: Animals, donors, MESH: Transplantation Conditioning, 0303 health sciences, Cell Differentiation, Hematology, severe combined immunodeficiency, Killer Cells, Natural, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, hematopoietic stem cell transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Transplantation Chimera, MESH: Cell Differentiation, MESH: Killer Cells, Natural, mice, bone marrow, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, MESH: Severe Combined Immunodeficiency, Biology, 03 medical and health sciences, MESH: B-Lymphocytes, medicine, Homologous chromosome, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH: Mice, B cell, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, Severe combined immunodeficiency, Transplantation Chimera, MESH: Humans, Compartment (ship), Cell Biology, medicine.disease, Hematopoietic Stem Cells, Transplantation, MESH: T-Lymphocytes, Bone marrow, 030215 immunology
Abstract

International audience; Severe combined immunodeficiency (SCID) is characterized by a complete block in T-lymphocyte differentiation. Most SCID also affects B-cell development or function, although a normal pool of pro-B cells is detectable. Treatment of SCID consists of allogeneic hematopoietic stem cell transplantation (HSCT), but in the absence of a myeloablative conditioning regimen, only T cells, and in some cases, natural killer (NK) cells, are of donor origin, while all other leukocytes subsets are of host origin. We hypothesized that donor B-cell development success could be conditioned by the competitive ability of recipient B-cell precursors in the bone marrow. We therefore compared the outcome of unconditioned HSCT in mice that differed with respect to their pro-B-cell compartments. B-cell reconstitution was limited in recipient mice containing a normal pro-B-cell pool, whereas immature and mature B-cell numbers reached wild-type levels in mice with compromised early B-cell precursors. Interestingly, host NK cells did not modify the outcome of unconditioned HSCT as long as the early B-cell compartment was compromised. These observations suggest that recipient B-cell precursors condition the reconstitution of the donor B-cell pool and, if extrapolative to humans, suggest that conditioning regimens targeting host pro-B cells may help improve B-cell reconstitution after allogeneic HSCT.

Published
2006
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50. Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia

Author

Ducastelle, S., Adès, L., Gardin, C., Dombret, H., Prébet, T., Eric DECONINCK, Rio, B., Thomas, X., Debotton, S., Guerci, A., Gratecos, N., Stamatoullas, A., Fegueux, N., Dreyfus, F., Fenaux, P., Wattel, E., Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Hématologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Virologie et pathogenèse virale (VPV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Saas, Philippe

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, autologous stem cell transplantation, Adolescent, MESH: Survival Rate, Antineoplastic Agents, Transplantation, Autologous, Time, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Aged, MESH: Adolescent, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Time, intensive chemotherapy, MESH: Adult, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Follow-Up Studies, Middle Aged, MESH: Transplantation, Autologous, MESH: Male, myelodysplastic syndrome, Survival Rate, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, MESH: Antineoplastic Agents, Female, MESH: Stem Cell Transplantation, MESH: Leukemia, Myeloid, Acute, MESH: Myelodysplastic Syndromes, MESH: Female, Follow-Up Studies, Stem Cell Transplantation
Abstract

International audience; We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS, autografted in first complete remission. Five (9.4%) died from the procedure whereas hematological reconstitution occurred in all the remaining patients. Forty patients (75%) relapsed, with 87.5% of the relapses occurring within 2 years of the autologous transplant. With a median follow-up of 6.2 years, the median actuarial disease-free survival and overall survival were 8 and 17 months after autograft, respectively. Karyotype was the only prognostic factor for disease-free and overall survival. The eight survivors (15%), including two patients with unfavorable or intermediate karyotype, remained in first complete remission 50+ to 119+ months after transplantation and are probably cured.

Published
2006

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