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.
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.
Morishima
Yasuo
Y
Department of Hematology and Chemotherapy, the Division of Epidemiology and Prevention, Aichi Cancer Center, Japan. ymorisim@aichi-cc.jp
Sasazuki
Takehiko
T
Inoko
Hidetoshi
H
Juji
Takeo
T
Akaza
Tatsuya
T
Yamamoto
Ken
K
Ishikawa
Yoshihide
Y
Kato
Shunichi
S
Sao
Hiroshi
H
Sakamaki
Hisashi
H
Kawa
Keisei
K
Hamajima
Nobuyuki
N
Asano
Shigetaka
S
Kodera
Yoshihisa
Y
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
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents