HLA matching and hematopoietic cell transplant outcome

The development of accurate and reproducible high-resolution DNA-based HLA typing methods has significantly improved the prospects for identifying well-matched donors for patients undergoing HCT, particularly those who lack a matched relative to serve as donor. Analysis of high-resolution typing data has shown that donor-recipient compatibility for HLA alleles is an important predictor of transplant outcome. The risk of graft failure is increased by patient incompatibility for HLA alleles expressed by the donor, and by the presence of patient anti-donor alloantibody. The impact of HLA class I and class II allele disparity on transplant outcome in unrelated HCT has been demonstrated in several large studies, and it is now evident that complete donor-recipient matching for HLA-A,-B,-C,-DRB1 and -DQB1 genes can significantly reduce the incidence of GVHD and risk of mortality. Patient-donor disparity for multiple HLA class I and class II alleles is clearly related to poor outcome, in terms of both risk of severe GVHD and mortality. Important questions for future investigation include elucidation of the relative importance of matching for different HLA genes ("permissive" versus "non-permissive" alleles), and the potential synergistic impact of multi-locus class I and II disparities.