title: The impact of graft-versus-host disease prophylaxis in reduced-intensity conditioning allogeneic stem cell transplant in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: The impact of the intensity of graft-versus-host-disease immunoprophylaxis on transplantation outcomes in patients undergoing transplantation following reduced-intensity conditioning is unclear. This study addresses this issue in 228 adult patients above 50 years of age with acute myeloid leukemia in first complete remission given peripheral blood stem cells from HLA-identical siblings after fludarabine and 2 days of intravenous busulfan reduced-intensity conditioning. A total of 152 patients received anti-thymocyte globulin, either in combination with cyclosporine A in 86 patients (group 1), or with cyclosporine A and mycophenolate mofetil or short course methotrexate in 66 patients (group 2). The remaining 76 patients did not receive anti-thymocyte globulin but were given cyclosporine A and methotrexate or mycophenolate mofetil (group 3). Incidences of grade II-IV acute graft-versus-host-disease were comparable in the three groups (16.5%, 29.5% and 19.5% in groups 1, 2 and 3, respectively, P=0.15). In multivariate analysis, the absence of anti-thymocyte globulin was the only factor associated with a higher risk of chronic graft-versus-host-disease (P=0.005), while the use of triple immunosuppression (group 3) was associated with an increased risk of relapse (P=0.003). In comparison to anti-thymocyte globulin and cyclosporine A alone, the other two strategies of graft-versus-host-disease prophylaxis were associated with reduced leukemia-free survival and overall survival (P=0.001 for each parameter), independently of the dose of anti-thymocyte globulin. These data suggest that fine tuning of the intensity of this prophylaxis can affect the outcome of transplantation and that anti-thymocyte globulin and cyclosporine A alone should be the preferred combination with the fludarabine-busulfan reduced-intensity conditioning regimen and sibling donors.
authors.affiliation: Hôpital Saint Antoine, Service d'Hématologie et de Thérapie Cellulaire, Paris, France Université Pierre et Marie Curie, Paris, France INSERM UMRs938, CDR Saint Antoine, Paris, France mt_rubio@hotmail.com.
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Rubio
authors.affiliation: Hôpital Saint Antoine, Service d'Hématologie et de Thérapie Cellulaire, Paris, France EBMT Data Office, Hôpital Saint Antoine, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Programme de Transplantation & Therapie Cellulaire Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Hôpital St. Louis, Dept. of Hematology - BMT, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.affiliation: IMIBIC/Reina Sofia Hospital, Cordoba, Spain.
authors.forename: Rafael Rojas
authors.initials: RR
authors.lastname: Contreras
authors.affiliation: CHU Nantes, Dept. D'Hématologie, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Hospital Universidad La Fe, Servicio de Hematologia y Oncologia, Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.affiliation: CHU Bordeaux, Hôpital Haut-leveque, Pessac, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Hôpital Purpan, CHU de Toulouse, Dept. Hematologie, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Department of Bone Marrow Transplantation, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Israel.
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.affiliation: Hôpital A. Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France.
authors.forename: Claude-Eric
authors.initials: CE
authors.lastname: Bulabois
authors.affiliation: Donostia Hospital, San Sebastian, Spain;
authors.forename: Nerea
authors.initials: N
authors.lastname: Caminos
authors.affiliation: Hospital Clinico, Servicio de Hematologia, Instituto Biosanitario de Salamanca (IBSAL), Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: López-Corral
authors.affiliation: Department of Bone Marrow Transplantation, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Israel EBMT Data Office, Hôpital Saint Antoine, Paris, France.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Hôpital Saint Antoine, Service d'Hématologie et de Thérapie Cellulaire, Paris, France Université Pierre et Marie Curie, Paris, France INSERM UMRs938, CDR Saint Antoine, Paris, France EBMT Data Office, Hôpital Saint Antoine, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011292:Premedication; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents