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8 results on '"MESH: Peripheral Blood Stem Cell Transplantation"'

1. Peripheral blood stem cell collection in elderly patients

Author

Ljubomir Petrov, Francoise Quivoron, Adrian Tempescul, Jean-Christophe Ianotto, Christian Berthou, Elisabeth Hardy, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), EFS Bretagne, Université européenne de Bretagne - European University of Brittany (UEB), and Michel, Geneviève

Subjects
medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphoma, CD34, Antigens, CD34, Cell Count, MESH: Multiple Myeloma, MESH: Peripheral Blood Stem Cell Transplantation, Peripheral Blood Stem Cells, MESH: Hematopoietic Stem Cell Mobilization, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Aged, Retrospective Studies, MESH: Age Factors, MESH: Aged, Peripheral Blood Stem Cell Transplantation, MESH: Humans, Hematology, MESH: Cell Count, business.industry, Age Factors, MESH: Retrospective Studies, Retrospective cohort study, MESH: Antigens, CD34, General Medicine, medicine.disease, Hematopoietic Stem Cell Mobilization, 3. Good health, Surgery, MESH: Blood Component Removal, Apheresis, Peripheral blood stem cell collection, 030220 oncology & carcinogenesis, Blood Component Removal, Feasibility Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, Multiple Myeloma, MESH: Feasibility Studies, MESH: Lymphoma, business, 030215 immunology
Abstract

International audience; Intensive treatments like autologous blood stem cell transplantations are standard consolidation treatments for lymphoma and myeloma in young people. The upper age limit for these procedures is constantly increasing. Instead of studying the impact of aging on harvesting peripheral blood stem cells (PBSC), we performed a retrospective study to explore the feasibility of collecting stem cells from patients older than 65 years and compared the efficacy to harvest in younger patients. During a period of 7 years, we identified 108 patients with myeloma or lymphoma who were older than 65 years who underwent PBSC collection. Only eight patients failed to produce a successful harvest. The majority of patients only needed one apheresis (71%). There was a median number of 5.3 x 10(6) CD34+ cells/kg. Our study demonstrated that older patients can also undergo PBSC harvests similar to younger patients.

Published
2009

2. Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study

Author

Bruno Lioure, Odile Blanchet, Christian Berthou, Mario Ojeda-Uribe, Jean-Luc Harousseau, Didier Bouscary, Martin Carre, Marie C. Béné, Fabrice Larosa, Mathilde Hunault, Isabelle Luquet, Luc Fornecker, Patrice Chevallier, Brigitte Witz, Norbert Ifrah, Didier Blaise, Pascale Cornillet-Lefebvre, Thierry Lamy, Jérôme Cornillon, Anne Huynh, Martine Delain, Arnaud Pigneux, Edouard Randriamalala, Nathalie Fegueux, Jean-Yves Cahn, Service d'onco-hématologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire d'hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), 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 Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, 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 [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), 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), 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), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and Université Joseph Fourier - Grenoble 1 (UJF)-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 Joseph Fourier - Grenoble 1 (UJF)-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)

Subjects
Male, MESH: Remission Induction, Transplantation Conditioning, Myeloid, medicine.medical_treatment, Graft vs Host Disease, Kaplan-Meier Estimate, Hematopoietic stem cell transplantation, MESH: Peripheral Blood Stem Cell Transplantation, Biochemistry, MESH: Proportional Hazards Models, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Cumulative incidence, MESH: Incidence, MESH: Bone Marrow Transplantation, Bone Marrow Transplantation, MESH: Transplantation Conditioning, MESH: Middle Aged, Incidence, Incidence (epidemiology), Remission Induction, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, MESH: Antineoplastic Combined Chemotherapy Protocols, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, MESH: Leukemia, Myeloid, Acute, medicine.medical_specialty, Immunology, MESH: Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, MESH: Hematopoietic Stem Cell Transplantation, MESH: Kaplan-Meier Estimate, Proportional Hazards Models, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, Proportional hazards model, Siblings, Cell Biology, medicine.disease, Confidence interval, MESH: Male, Surgery, MESH: Siblings, Transplantation, business, MESH: Female, 030215 immunology
Abstract

The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients. This study was registered at clinicaltrials.gov as no. NCT01015196.

Published
2012

3. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial

Author

Bui-Nguyen, B., Ray-Coquard, Isabelle, Chevreau, C., Penel, N., Bay, J. O., Coindre, J. M., Cupissol, D., Italiano, A., Bonichon, F., Lotz, J. P., Thyss, A., Jimenez, M., Mathoulin-Pélissier, S., Blay, J. Y., Renseigné, Non, Institut Bergogné, Department of Medical Oncology, Centre Léon Bérard [Lyon], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Centre Régional de Lutte Contre le Cancer Oscar Lambret, Centre Jean Perrin, CRLCC Jean Perrin, Institut bergogné, Centre Val d'Aurelle-Paul Lamarque, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Unité Matériaux et Transformations - UMR 8207 (UMET), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut National de la Recherche Agronomique (INRA), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Eq 11, Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, 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), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Chimie du CNRS (INC)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL)

Subjects
Male, MESH: Combined Modality Therapy, MESH: Consolidation Chemotherapy, MESH: Peripheral Blood Stem Cell Transplantation, Kaplan-Meier Estimate, Carboplatin, chemistry.chemical_compound, 0302 clinical medicine, MESH: Mesna, MESH: Carboplatin, Antineoplastic Combined Chemotherapy Protocols, Etoposide, Mesna, MESH: Etoposide, MESH: Aged, Ifosfamide, MESH: Middle Aged, Soft tissue sarcoma, Sarcoma, Hematology, Middle Aged, Chemotherapy regimen, Combined Modality Therapy, 3. Good health, Dacarbazine, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Dacarbazine, Disease-Free Survival, 03 medical and health sciences, MESH: Doxorubicin, Young Adult, medicine, Humans, Progression-free survival, MESH: Ifosfamide, MESH: Kaplan-Meier Estimate, Aged, MESH: Adolescent, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Male, Surgery, Consolidation Chemotherapy, chemistry, Doxorubicin, MESH: Sarcoma, MESH: Disease-Free Survival, business, MESH: Female, 030215 immunology
Abstract

International audience; BACKGROUND: Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. RESULTS: From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. CONCLUSION: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.

Published
2011

4. 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

5. Cost effectiveness of high-dose chemotherapy with autologous stem cell support as initial treatment of aggressive non-Hodgkin's lymphoma

Author

Fagnoni, Philippe, Milpied, Noel, Limat, Samuel, Deconinck, Eric, Nerich, Virginie, Foussard, Charles, Colombat, Philippe, Harousseau, Jean-Luc, Woronoff-Lemsi, Marie-Christine, Renseigné, Non, Service des maladies du sang, CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), 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), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, 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]), 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), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), and 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)

Subjects
Male, Oncology, MESH: Combined Modality Therapy, Time Factors, Cost effectiveness, Cost-Benefit Analysis, MESH: Peripheral Blood Stem Cell Transplantation, CHOP, International Prognostic Index, MESH: Lymphoma, Non-Hodgkin, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Randomized Controlled Trials as Topic, Lymphoma, Non-Hodgkin, Health Policy, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Combined Modality Therapy, Chemotherapy regimen, MESH: Transplantation, Autologous, MESH: Antineoplastic Combined Chemotherapy Protocols, Vincristine, Female, Rituximab, medicine.drug, Adult, medicine.medical_specialty, Prednisolone, MESH: Vincristine, Transplantation, Autologous, MESH: Doxorubicin, Internal medicine, Humans, Cyclophosphamide, Pharmacology, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, MESH: Time Factors, Public Health, Environmental and Occupational Health, MESH: Cyclophosphamide, MESH: Adult, medicine.disease, MESH: Male, Surgery, Non-Hodgkin's lymphoma, Transplantation, MESH: Randomized Controlled Trials as Topic, Doxorubicin, business, MESH: Prednisolone, MESH: Female, MESH: Cost-Benefit Analysis
Abstract

Background: The GOELAMS 072 study showed that first-line high-dose chemotherapy (HDT) with peripheral blood stem cell transplant (PBSCT) support was superior to the standard chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP) in adults with aggressive non-Hodgkin's lymphoma (NHL). Objective: The aim of the study was to evaluate the pharmacoeconomic profile of HDT with PBSCT support relative to standard CHOP therapy as first-line treatment in adults with aggressive NHL. Methods: We performed a cost-effectiveness analysis from the French Public Health Insurance perspective, restricted to hospital costs (€, year 2008 values). The clinical effectiveness criterion was censured overall survival (OS) difference after a median follow-up of 4 years for the entire cohort. A total of 197 patients were included (CHOP, n - 99; HDT, n - 98). Uncertainty was assessed using non-parametric bootstrap simulations and various scenario analyses. Results: Five-year OS did not differ significantly between groups for the entire cohort. Nevertheless, subgroup analyses appeared to be more relevant for decision making: among patients with a high-intermediate risk according to the age-adjusted International Prognostic Index (IPI), HDT yielded a significantly higher 5-year OS than CHOP (74% vs 44%; p - 0.001). Among these patients, the mean censured OS survival, adjusted for time discounting and quality of life (QOL), increased with HDT by 1.20 years (95% CI 1.19, 1.21). The cost per life-year saved with HDT was estimated as €34 315 (95% CI 32 683, 35 947) in this subgroup. Conclusion: Results suggested that HDT with PBSCT support might be considered a cost-effective strategy among patients with high-intermediate-risk NHL according to the age-adjusted IPI. Its place and its cost effectiveness potential versus, or in combination with, rituximab still need further research.

Published
2009

6. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia

Author

Stephen Pavletic, Robert Peter Gale, Mukta Arora, Vikas Gupta, Haydar Frangoul, Dan Wang, Jon J. van Rood, Pierre Tiberghien, Gregory A. Hale, Philip L. McCarthy, John T. Horan, Luis Isola, Joerg Halter, Richard T. Maziarz, Mark R. Litzow, Vijay Reddy, Olle Ringdén, Theresa Hahn, Mei-Jie Zhang, Claudio Anasetti, Roswell Park Cancer Institute [Buffalo], Medical College of Wisconsin, University of Minnesota System, Mayo Clinic, Vanderbilt University [Nashville], St Jude Children's Research Hospital, Department of Pharmacology, Emory University [Atlanta, GA], Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Oregon Health and Science University [Portland] (OHSU), Leiden University Medical Center (LUMC), Princess Margaret Hospital, University of Toronto, University Hospital Basel [Basel], Florida Hospital Cancer Institute, 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]), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Karolinska University Hospital [Stockholm], 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, Cancer Research, Time Factors, Graft vs Host Disease, MESH: Peripheral Blood Stem Cell Transplantation, MESH: Risk Assessment, Severity of Illness Index, 0302 clinical medicine, MESH: Risk Factors, HLA Antigens, Risk Factors, Living Donors, Cumulative incidence, MESH: Bone Marrow Transplantation, MESH: HLA Antigens, MESH: Treatment Outcome, Bone Marrow Transplantation, MESH: Living Donors, Leukemia, Histocompatibility Testing, Myeloid leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, MESH: Reproducibility of Results, Europe, Leukemia, Myeloid, Acute, surgical procedures, operative, Treatment Outcome, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Leukemia, Myeloid, Acute, medicine.drug, Adult, medicine.medical_specialty, Canada, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cyclophosphamide, Adolescent, MESH: Graft vs Host Disease, MESH: Histocompatibility Testing, Risk Assessment, 03 medical and health sciences, Myelogenous, Young Adult, MESH: Canada, Internal medicine, Acute lymphocytic leukemia, MESH: Severity of Illness Index, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, MESH: Leukemia, medicine, MESH: United States, Humans, Risk factor, Retrospective Studies, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, Siblings, MESH: Time Factors, Reproducibility of Results, MESH: Retrospective Studies, MESH: Adult, medicine.disease, MESH: Male, United States, MESH: Siblings, Graft-versus-host disease, MESH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Immunology, MESH: Europe, business, MESH: Female, 030215 immunology
Abstract

Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.

Published
2008

7. Soluble human leucocyte antigen-G molecules in peripheral blood haematopoietic stem cell transplantation: a specific role to prevent acute graft-versus-host disease and a link with regulatory T cells

Author

Laurence Amiot, Gilbert Semana, Marc Bernard, J.-M. Grosset, Brigitte Birebent, Nicolas Vu, S. De Guibert, G. Noël, A. Le Maux, Microenvironnement cellulaire et moléculaire des tumeurs, Université de Rennes (UR), Etablissement Français du Sang Bretagne, EFS, Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue contre le Cancer (Ille et Vilaine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1)

Subjects
Translational Studies, sHLA-G, Graft vs Host Disease, natural regulatory T cell, MESH: Peripheral Blood Stem Cell Transplantation, immunomodulation, T-Lymphocytes, Regulatory, MESH: Histocompatibility Antigens Class I, Blood cell, Cohort Studies, 0302 clinical medicine, HLA Antigens, immune system diseases, graft-versus-host disease, Immunology and Allergy, IL-2 receptor, MESH: Cohort Studies, MESH: HLA Antigens, 0303 health sciences, Prognosis, 3. Good health, Haematopoiesis, medicine.anatomical_structure, surgical procedures, operative, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, MESH: Immune Tolerance, Regulatory T cell, Immunology, MESH: Graft vs Host Disease, MESH: HLA-G Antigens, MESH: Prognosis, 03 medical and health sciences, MESH: Lymphocyte Culture Test, Mixed, medicine, Immune Tolerance, Humans, 030304 developmental biology, HLA-G Antigens, MESH: Humans, business.industry, MESH: T-Lymphocytes, Regulatory, Histocompatibility Antigens Class I, MESH: Biological Markers, T lymphocyte, medicine.disease, Transplantation, MESH: Solubility, Graft-versus-host disease, Solubility, peripheral blood stem cell transplantation, Lymphocyte Culture Test, Mixed, business, Biomarkers, 030215 immunology
Abstract

SummaryHaematopoietic stem cell transplantation is often complicated by the life-threatening graft-versus-host disease (GVHD) which consists of an allogeneic reaction of the graft cells against the host organs. The aim of this study was to investigate the putative involvement of soluble human leucocyte antigen (sHLA) class I molecules, and particularly sHLA-G molecules, in the occurrence and/or prevention of acute GVHD (aGVHD) in allogeneic peripheral blood stem cell (PSC) transplantation. Whole sHLA class I molecules seem to be involved in aGVHD pathogenesis because detection of a high concentration of these molecules in the first month post allograft is correlated with aGVHD occurrence. Conversely, a high level of sHLA-G molecules before and after allograft could indicate good prognosis in PSC allograft transplantation. sHLA-G molecules seem to be involved in aGVHD prevention, not only because they are enriched in plasma of patients without aGVHD, but also because: (i) a positive correlation has been found between sHLA-G level and CD4+ CD25+ CD152+ natural regulatory T cell (Treg) frequency in the blood of transplanted patients; and (ii) the presence of CD4+ CD25+ CD152+ natural Treg is correlated with increased sHLA-G expression in in vitro mixed leucocyte reaction cultures. Altogether, these results support the immunomodulatory function of sHLA-G molecules that might create a regulatory network together with the natural Treg to foster the induction of a tolerogenic environment and improve PSC transplantation favourable outcome.

Published
2008

8. Skin involvement in scleroderma--where histological and clinical scores meet

Author

Raphaël Porcher, Laurence Michel, Patrick Bruneval, Franck Verrecchia, Kiet Phuong Tiev, M. Ertault, O. Verola, Dominique Farge, Alain Mauviel, Nina Roos, J. Laboureau, Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biostatistique et épidemiologie clinique, Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service greffe de moelle osseuse, Service de médecine interne, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service de Médecine Interne [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine interne [CHU Saint-Antoine], and Verrecchia, Franck

Subjects
Male, Pathology, Systemic disease, MESH: Combined Modality Therapy, MESH : Peripheral Blood Stem Cell Transplantation, Biopsy, MESH : Aged, Smad Proteins, MESH: Peripheral Blood Stem Cell Transplantation, Systemic scleroderma, Severity of Illness Index, Scleroderma, Immunoenzyme Techniques, MESH: Biopsy, 0302 clinical medicine, Fibrosis, Transforming Growth Factor beta, Immunopathology, MESH: Collagen, Pharmacology (medical), MESH: Double-Blind Method, MESH : Female, Phosphorylation, MESH : Immunosuppressive Agents, Cells, Cultured, Skin, MESH: Aged, 0303 health sciences, MESH: Phosph, MESH: Middle Aged, medicine.diagnostic_test, integumentary system, Middle Aged, MESH : Adult, Connective tissue disease, Combined Modality Therapy, 3. Good health, MESH: Fibrosis, MESH : Fibrosis, Female, Collagen, MESH: Immunosuppressive Agents, Reticular Dermis, Immunosuppressive Agents, Signal Transduction, MESH: Cells, Cultured, Adult, medicine.medical_specialty, MESH : Male, Collagen Type I, 03 medical and health sciences, Rheumatology, Double-Blind Method, MESH : Immunoenzyme Techniques, Plasminogen Activator Inhibitor 1, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH : Double-Blind Method, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Middle Aged, RNA, Messenger, Smad3 Protein, MESH: Immunoenzyme Techniques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, MESH : Phosph, MESH : Humans, MESH: Adult, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Fibroblasts, medicine.disease, MESH: Male, MESH: Fibroblasts, MESH : Biopsy, Scleroderma, Diffuse, MESH : Collagen, business, MESH : Combined Modality Therapy, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Female, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; OBJECTIVES: A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS). METHODS: Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT). RESULTS: Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies). CONCLUSIONS: The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.

Published
2007

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