| Budget Amount *help |
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of HLA alleles responsible for immunological 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 HLA-A, B, C or DRB1 allele were independent risk factors for acute GVHD, and a synergistical effect of HLA-C allele mismatch with other HLA allele mismatch on acute GVHD was remarkable. HLA-A and/or 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 B allele mismatch reduced overall survival remarkably in both standard and high risk leukemia cases, while the HLA-C mismatch or HLA-class II (DRB 1 and/or DQB 1) mismatch did not. Furthermore, multiple mismatch of HLA locus was found to reduce survival in leukemia cases. Thus, the role of HLA class I allele in unrelated BMT was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or B alleles for acute GVHD and survival. Epitope matching of NK cell receptors, such as killer cell Ig-like receptors (KIR) had a role for the induction of acute GVHD by NK cells.
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