Background The requirements with respect to HLA compatibilityand the relative importance of matching for individual classI and class II HLA alleles in the transplantation of hematopoieticstem cells from unrelated donors have not yet been established.
Methods We performed retrospective DNA typing of alleles at11 polymorphic loci of HLA genes in 440 recipients of hematopoieticstem cells from unrelated donors who were serologically identicalwith their respective recipients for HLA-A, B, and DR antigens.Of these recipients, 80 percent had leukemia; the rest had lymphoma,marrow failure, or a congenital disorder.
Results Multivariate analysis showed that incompatibility forHLA-A alleles and incompatibility for HLA-C alleles were independentrisk factors for severe acute graft-versus-host disease (GVHD)(HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, butnot of HLA-C, alleles was an independent risk factor for death(P<0.001). Mismatching of HLA-C alleles was a significantrisk factor for relapse of leukemia (P=0.035). HLA-B disparitywas a significant risk factor for both GVHD and death in theunivariate analysis, but not in the multivariate analysis. Disparitiesin class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1loci were not identified as significant risk factors for acuteGVHD or death in the multivariate analysis.
Conclusions Genomic typing of class I HLA alleles adds substantiallyto the success of transplantation of hematopoietic stem cellsfrom unrelated donors, even if the donors are serologicallyidentical to their recipients with respect to HLA-A, B, andDR antigens.
Source Information
From the Department of Genetics, Medical Institute of Bioregulation (T.S., N. Kamikawaji), and the Department of Medical Informatics, Faculty of Medicine (N. Kinukawa), Kyushu University, Fukuoka; the Japanese Red Cross Central Blood Center, Tokyo (T.J., T.A.); the Department of Hematology and Chemotherapy, Aichi Cancer Center Hospital, Nagoya (Y.M.); the Department of Surgery, Sakura National Hospital, Chiba (H.K.); the Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Kanagawa (H.I.); the Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo (T.Y.); the Department of Tissue Physiology, Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University, Tokyo (A.K.); the Department of Internal Medicine, Japanese Red Cross Nagoya First Hospital, Nagoya (Y.K.); and Jichi Medical School, Tochigi (F.T.) — all in Japan. Other authors were Yoshiaki Nose, M.D., Ph.D. (Department of Medical Informatics, Faculty of Medicine, Kyushu University), Takashi Ono, M.D. (Department of Genetics, Medical Institute of Bioregulation, Kyushu University), Takeo Sakamaki, M.D., Ph.D. (Division of Clinical Research, Sakura National Hospital), Shunichi Kato, M.D., Ph.D. (Department of Pediatrics, Tokai University School of Medicine), Yuichi Akiyama, M.D. (Department of Pediatrics, Kyoto University School of Medicine, Kyoto), Shinichiro Okamoto, M.D., Ph.D. (Department of Medicine, Keio University School of Medicine, Tokyo), Hiroo Dohy, M.D., Ph.D. (Department of Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima), Mine Harada, M.D., Ph.D. (Second Department of Internal Medicine, Okayama University School of Medicine, Okayama), and Shigetaka Asano, M.D., Ph.D. (Institute of Medical Science, Tokyo University, Tokyo).
Address reprint requests to Dr. Sasazuki at the Department of Genetics, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
Hematopoietic Stem-Cell Transplantation for Acute Leukemia
Eiermann T. H., van Bekkum D. W., Vriesendorp H. M., Machida U., Kami M., Hirai H., Bolan C. D., Leitman S. F., Sasazuki T., Juji T., Kodera Y., Aversa F., Martelli M. F., Reisner Y.
Extract |
Full Text
N Engl J Med 1999;
340:809-812, Mar 11, 1999.
Correspondence
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A correction has been published: N Engl J Med 1999;340(5):402.
