Publication Date:
2013-11-15
Description:
Background Although the effect of allele matching of each HLA locus on the clinical outcome of unrelated hematopoietic stem cell transplantation (UR-HSCT) has been characterized, the effect of HLA allele or haplotype (HP) itself has not been well elucidated. The HLA region is recognized as one of the most important genetic regions associated with human disease, especially autoimmune and infectious diseases. We therefore hypothesized that the immunological response and the clinical outcome following UR-HSCT depend not only on HLA allele matching but also on the HLA allele itself or HLA-linked genetic background of the patient and donor. Methods We analyzed 5237 patients who received T-cell-replete bone marrow transplants from serologically HLA-A, -B, and -DR antigen-matched unrelated donors facilitated by the Japan Marrow Donor Program between 1993 and 2008. HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively genotyped. HLA allele frequencies were calculated by direct counting, and multi-locus HLA HP frequencies were estimated using the maximum-likelihood method with EM algorithm of PyPop software. Patients were stratified by HLA-matching status into a full match (FM) group (12/12-matched, n=733) and a mismatch (MM) group (≤11/12-matched, n=4504). The effect of HLA alleles or HPs with a frequency greater than 5% on acute graft-versus-host disease (aGVHD) and overall survival (OS) was analyzed using a multivariate competing risk regression model. The results are expressed as hazard ratios (HRs) comparing specific allele/haplotype-positive group to -negative group. Results For each allele, the number of HLA alleles significantly associated with aGVHD (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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