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

نویسندگان

  • Yasuo Morishima
  • Koichi Kashiwase
  • Keitaro Matsuo
  • Fumihiro Azuma
  • Satoko Morishima
  • Makoto Onizuka
  • Toshio Yabe
  • Makoto Murata
  • Noriko Doki
  • Tetsuya Eto
  • Takehiko Mori
  • Koichi Miyamura
  • Hiroshi Sao
  • Tatsuo Ichinohe
  • Hiroo Saji
  • Shunichi Kato
  • Yoshiko Atsuta
  • Keisei Kawa
  • Yoshihisa Kodera
  • Takehiko Sasazuki
چکیده

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 HLA-DQB1 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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عنوان ژورنال:
  • Blood

دوره 125 7  شماره 

صفحات  -

تاریخ انتشار 2015