HLA mismatch combinations associated with decreased risk of relapse: Implications for the molecular mechanism

Takakazu Kawase, Keitaro Matsuo, Koichi Kashiwase, Hidetoshi Inoko, Hiroh Saji, Seishi Ogawa, Shunichi Kato, Takehiko Sasazuki, Yoshihisa Kodera, Yasuo Morishima

研究成果: Contribution to journalArticle査読

109 被引用数 (Scopus)

抄録

The finding that the risk of relapse in hematologic malignancy decreases after allogeneic hematopoietic stem cell transplantation (HSCT) has lead to the concept of a graft-versus-leukemia (GVL) effect. However, this beneficial effect is considered to be frequently offset by graft- versus-host disease (GVHD). Thus, improving HSCT outcomes by separating GVL from GVHD is a key clinical issue. This cohort study registered 4643 patients with hematologic malignancies who received transplants from unrelated do nors. Six major human leukocyte antigen (HLA) loci were retrospectively geno- typed. We identified 4 HLA-Cw and 6 HLA- DPB1 mismatch combinations responsible for a decreased risk of relapse; of these, 8 of 10 combinations were different from those responsible for severe acute GVHD, including all 6 of the HLA-DPB1 combinations. Pairs with these combinations of HLA-DPB1 were associated with a significantly better overall survival than were completely matched pairs. Moreover, several amino acid substitutions on specific positions responsible for a decreased risk of relapse were identified in HLA-Cw, but not in HLA-DPB1. These findings might be crucial to elucidating the mechanism of the decreased risk of relapse on the basis of HLA molecule. Donor selection made in consideration of these results might allow the separation of GVL from acute GVHD, especially in HLA-DPB1 mismatch combinations.

本文言語英語
ページ(範囲)2851-2858
ページ数8
ジャーナルBlood
113
12
DOI
出版ステータス出版済み - 3 19 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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