Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n 5 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy 6 Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P 5 .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n 5 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P 5 .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P, .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged .30 years after HLA-matched sibling (HR, 2.74; P, .001) or unrelated donor (HR, 1.98; P 5 .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.
Bibliographical noteFunding Information:
1Department of Blood and Marrow Transplant and Cellular Therapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; 2Division of Biostatistics and 3Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; 4The Ottawa Hospital Blood & Marrow Transplant Program, University of Ottawa, Ottawa, ON, Canada; 5Children’s Center for Cancer and Blood Diseases, Children’s Hospital of Los Angeles, Los Angeles, CA; 6Division of Pediatric Hematology/Oncology, Children’s Mercy Hospital, Kansas City, MO; 7King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 8Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University, Evanston, IL; 9Department of Medicine, University of Miami, Miami, FL; 10Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY; 11Hospital Niño Jesus, Madrid, Spain; 12Division of Pediatric Blood and Marrow Transplantation, University of California San Francisco Medical Center, San Francisco, CA; 13Clinical Genetics Branch, National Cancer Institute, Rockville, MD; 14Department of Medicine, Oregon Health & Science University, Portland, OR; 15Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom; 16Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas, Kansas City, KS; 17Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; 18Department of Hematology, Christian Medical College Hospital, Vellore, India; 19Department of Medicine, Weill Cornell Medical College, New York, NY; 20HospitalUniversitarioJoséE.González,UniversidadAutónomadeNuevoLeón,Monterrey,Mexico;21DivisionofHematologyandOncology,NationwideChildren’sHospital, Columbus, OH; 22Department of Medicine. Baylor College of Medicine Center for Cell and Gene Therapy, Houston, TX; 23Department of Pediatrics, University of North Carolina Hospitals, Chapel Hill, NC; 24Department of Medicine, Case Western Reserve University, Cleveland, OH; 25Department of Medicine, University of Minnesota, Minneapolis, MN; 26Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden; 27British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada; 28Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada; 29Fred Hutchinson Cancer Research Center, Seattle, WA; 30Children’s National Medical Center, Washington, DC; 31Vanderbilt University Medical Center, Nashville, TN; 32Greenebaum Cancer Center, University of Maryland, Baltimore, MD; and 33Stem Cell Transplantation, Dana-Farber Cancer Institute, Boston, MA.
The Center for International Blood and Marrow Transplant Research is supported by U24-CA76518 from the National Institutes of Health, National Cancer Institute, National Heart, Lung, and Blood Institute, and National Institute of Allergy and Infectious Diseases, and HHSH 250201200016C from Health Services Research Administration, Department of Health and Human Services.
© 2019 American Society of Hematology. All rights reserved.