Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

Japan Marrow Donor Program

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLADQB1 double (DRB1-DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1-DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1-DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.

Original languageEnglish
Pages (from-to)1189-1197
Number of pages9
JournalBlood
Volume125
Issue number7
DOIs
Publication statusPublished - Feb 12 2015

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Unrelated Donors
Graft vs Host Disease
Bone Marrow Transplantation
Grafts
Bone
HLA-A Antigens
HLA-B Antigens
HLA-C Antigens
Transplants
Leukemia
Alleles
HLA-DRB1 Chains
Donor Selection
Histocompatibility Testing
Mortality
T-cells
Transplantation
Bone Marrow
Regression Analysis
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Biological significance of HLA locus matching in unrelated donor bone marrow transplantation. / Japan Marrow Donor Program.

In: Blood, Vol. 125, No. 7, 12.02.2015, p. 1189-1197.

Research output: Contribution to journalArticle

Japan Marrow Donor Program. / Biological significance of HLA locus matching in unrelated donor bone marrow transplantation. In: Blood. 2015 ; Vol. 125, No. 7. pp. 1189-1197.
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title = "Biological significance of HLA locus matching in unrelated donor bone marrow transplantation",
abstract = "We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLADQB1 double (DRB1-DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1-DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1-DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.",
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AU - Japan Marrow Donor Program

AU - Morishima, Yasuo

AU - Kashiwase, Koichi

AU - Matsuo, Keitaro

AU - Azuma, Fumihiro

AU - Morishima, Satoko

AU - Onizuka, Makoto

AU - Yabe, Toshio

AU - Murata, Makoto

AU - Doki, Noriko

AU - Eto, Tetsuya

AU - Mori, Takehiko

AU - Miyamura, Koichi

AU - Sao, Hiroshi

AU - Ichinohe, Tatsuo

AU - Saji, Hiroo

AU - Kato, Shunichi

AU - Atsuta, Yoshiko

AU - Kawa, Keisei

AU - Kodera, Yoshihisa

AU - Sasazuki, Takehiko

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N2 - We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLADQB1 double (DRB1-DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1-DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1-DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.

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