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, Yoshihisa Kodera

Research output: Contribution to journalArticle

339 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4200-4206
Number of pages7
JournalBlood
Volume99
Issue number11
DOIs
Publication statusPublished - Jun 1 2002

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Unrelated Donors
Transplants
HLA Antigens
Bone Marrow
Alleles
Grafts
Graft vs Host Disease
Leukemia
Survival
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

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. / Morishima, Yasuo; Sasazuki, Takehiko; Inoko, Hidetoshi; Juji, Takeo; Akaza, Tatsuya; Yamamoto, Ken; Ishikawa, Yoshihide; Kato, Shunichi; Sao, Hiroshi; Sakamaki, Hisashi; Kawa, Keisei; Hamajima, Nobuyuki; Asano, Shigetaka; Kodera, Yoshihisa.

In: Blood, Vol. 99, No. 11, 01.06.2002, p. 4200-4206.

Research output: Contribution to journalArticle

Morishima, Y, Sasazuki, T, Inoko, H, Juji, T, Akaza, T, Yamamoto, K, Ishikawa, Y, Kato, S, Sao, H, Sakamaki, H, Kawa, K, Hamajima, N, Asano, S & Kodera, Y 2002, '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', Blood, vol. 99, no. 11, pp. 4200-4206. https://doi.org/10.1182/blood.V99.11.4200
Morishima, Yasuo ; Sasazuki, Takehiko ; Inoko, Hidetoshi ; Juji, Takeo ; Akaza, Tatsuya ; Yamamoto, Ken ; Ishikawa, Yoshihide ; Kato, Shunichi ; Sao, Hiroshi ; Sakamaki, Hisashi ; Kawa, Keisei ; Hamajima, Nobuyuki ; Asano, Shigetaka ; Kodera, Yoshihisa. / 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. In: Blood. 2002 ; Vol. 99, No. 11. pp. 4200-4206.
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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.",
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AU - Inoko, Hidetoshi

AU - Juji, Takeo

AU - Akaza, Tatsuya

AU - Yamamoto, Ken

AU - Ishikawa, Yoshihide

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AU - Sao, Hiroshi

AU - Sakamaki, Hisashi

AU - Kawa, Keisei

AU - Hamajima, Nobuyuki

AU - Asano, Shigetaka

AU - Kodera, Yoshihisa

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