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
Marie Thérèse Rubio,
Myriam Labopin,
Didier Blaise,
Gerard Socié,
Rafael Rojas Contreras,
Patrice Chevallier,
Miguel A. Sanz,
Stéphane Vigouroux,
Anne Huynh,
Avichai Shimoni,
Claude-Eric Bulabois,
Nerea Caminos,
Lucía López-Corral,
Arnon Nagler,
Mohamad Mohty
Affiliations
Marie Thérèse Rubio
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
Myriam Labopin
Hôpital Saint Antoine, Service d’Hématologie et de Thérapie Cellulaire, Paris, France;EBMT Data Office, Hôpital Saint Antoine, Paris, France
Didier Blaise
Programme de Transplantation & Therapie Cellulaire Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France
Gerard Socié
Hôpital St. Louis, Dept. of Hematology - BMT, Paris, France
Rafael Rojas Contreras
IMIBIC/Reina Sofia Hospital, Cordoba, Spain
Patrice Chevallier
CHU Nantes, Dept. D’Hématologie, France
Miguel A. Sanz
Hospital Universidad La Fe, Servicio de Hematologia y Oncologia, Valencia, Spain
Stéphane Vigouroux
CHU Bordeaux, Hôpital Haut-leveque, Pessac, France
Anne Huynh
Hôpital Purpan, CHU de Toulouse, Dept. Hematologie, France
Avichai Shimoni
Department of Bone Marrow Transplantation, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Israel
Claude-Eric Bulabois
Hôpital A. Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France
Nerea Caminos
Donostia Hospital, San Sebastian, Spain;
Lucía López-Corral
Hospital Clinico, Servicio de Hematologia, Instituto Biosanitario de Salamanca (IBSAL), Spain.
Arnon Nagler
Department of Bone Marrow Transplantation, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Israel;EBMT Data Office, Hôpital Saint Antoine, Paris, France
Mohamad Mohty
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
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.
