JOURNAL ARTICLE

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

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
Blood 2015 February 12, 125 (7): 1189-97
25519752
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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