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Blood, 1 June 2002, Vol. 99, No. 11, pp. 4200-4206
TRANSPLANTATION
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
Yasuo Morishima,
Takehiko Sasazuki,
Hidetoshi Inoko,
Takeo Juji,
Tatsuya Akaza,
Ken Yamamoto,
Yoshihide Ishikawa,
Shunichi Kato,
Hiroshi Sao,
Hisashi Sakamaki,
Keisei Kawa,
Nobuyuki Hamajima,
Shigetaka Asano, and
Yoshihisa Kodera for the Japan
Marrow Donor Program
From the Department of Hematology and Chemotherapy, the
Division of Epidemiology and Prevention, Aichi Cancer Center; the
Department of Genetics, Medical Institute of Bioregulation, Kyushu
University; the Department of Genetic Information, the Division of
Molecular Science, the Department of Pediatrics, Tokai University
School of Medicine; the Japanese Red Cross Central Blood Center; the
Department of Hematology, Meitetsu Hospital; the Department of
Hematology, Tokyo Metropolitan Hospital; the Department of Pediatrics,
Osaka Medical Center for Maternal and Child Health; Institute of
Medical Science, Tokyo University; and the Department of Internal
Medicine, Japanese Red Cross Nagoya First Hospital, Japan.
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.
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