Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors
We have examined the alleles of eleven minor histocompatibility antigens (MiHAs) and investigated the occurrence of immunogenic MiHA disparities in 62 recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning performed between 2000 and 2008 and in their HLA-matched sibling donors. Immunogenic MiHA mismatches were detected in 42 donor-recipient pairs: in 29% MiHA was mismatched in HVG direction, in another 29% in GVH direction; bidirectional MiHA disparity was detected in 10% and no MiHA mismatches in 32%. Patients with GVH-directed HY mismatches had lower both overall survival and disease-free survival at 3 years than patients with compatible HY; also higher incidence of both severe acute GvHD and extensive chronic GVHD was observed in patients with GVH-directed HY mismatch. On contrary, GVH-directed mismatches of autosomally encoded MiHAs had no negative effect on overall survival. Results of our study help to understand why posttransplant courses of allo-HCT from siblings may vary despite the complete high-resolution HLA matching of a donor and a recipient. 1. Introduction The allogeneic hematopoietic cell transplantation (allo-HCT) still remains a curative treatment of many severe diseases, especially hematooncological malignancies. The successful donor search is one of the most important factors deciding about the feasibility of transplantation. It starts with search among the patient’s siblings as the HLA-matched sibling donor is regarded as the optimal one. The odds ratio for HLA compatibility in siblings is 1？:？4. The probability of having a matched sibling donor by a particular patient is determined by the formula , where equals the number of siblings. Despite the improved matching of donor-recipient pairs that was possible after the implementation of high-resolution methods of molecular HLA typing, the better outcomes of transplantations are still limited by high number of complications: graft versus host disease (GVHD), engraftment problems (lack or loss of engraftment), and relapse [1]. The long-term survival after allo-HCT is being estimated in the range of 40–70%. Failures are mainly due to infectious complications and GVHD (30–40% each), organ toxicity of chemotherapy (20%), and relapse (20–30%) [2]. HLA matching remains the most important factor influencing both donor selection and transplantation outcomes. However, research of the human genome revealed that polymorphism of nucleotides in genes that are non-HLA related (e.g., NOD2/CARD15 or genes encoding cytokines: TNF-alpha, IL-10, IL-6,
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