title: The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors.
abstract: To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of human leukocyte antigen (HLA) alleles responsible for immunologic events such as graft-versus-host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively performed in 1298 donor-patient pairs in cases where marrow was donated from serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA-A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the synergistic effect of the HLA-C allele mismatch with other HLA allele mismatches on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be a significant factor for the occurrence of chronic GVHD. HLA class I (A, B, and/or C) allele mismatch caused a significantly higher incidence of engraftment failure than HLA match. Significant association of HLA-C allele mismatch with leukemia relapse was not observed. As the result of these events, HLA-A and/or HLA-B allele mismatch reduced overall survival remarkably in both standard-risk and high-risk leukemia cases, whereas the HLA-C mismatch or HLA-class II (DRB1 and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus was found to reduce survival in leukemia cases. Thus, the role of the HLA class I allele in unrelated bone marrow transplantation was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or -B alleles for acute GVHD and survival.
authors: Department of Hematology and Chemotherapy, the Division of Epidemiology and Prevention, Aichi Cancer Center, Japan. ymorisim@aichi-cc.jp
authors: Yasuo
authors: Y
authors: Morishima
authors: Takehiko
authors: T
authors: Sasazuki
authors: Hidetoshi
authors: H
authors: Inoko
authors: Takeo
authors: T
authors: Juji
authors: Tatsuya
authors: T
authors: Akaza
authors: Ken
authors: K
authors: Yamamoto
authors: Yoshihide
authors: Y
authors: Ishikawa
authors: Shunichi
authors: S
authors: Kato
authors: Hiroshi
authors: H
authors: Sao
authors: Hisashi
authors: H
authors: Sakamaki
authors: Keisei
authors: K
authors: Kawa
authors: Nobuyuki
authors: N
authors: Hamajima
authors: Shigetaka
authors: S
authors: Asano
authors: Yoshihisa
authors: Y
authors: Kodera
mesh_terms: D000328:Adult; D000483:Alleles; D000741:Anemia, Aplastic / Q000628:therapy; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000628:therapy; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy; D008297:Male; D009190:Myelodysplastic Syndromes / Q000628:therapy; D012008:Recurrence; D012189:Retrospective Studies; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents