Abstract

HLA haplotype mismatches have been linked to an increased risk of acute graft-versus-host disease (aGVHD) in patients receiving hematopoietic cell transplants from unrelated donors who are HLA-matched (HCT). Gamma block (GB) comprises many inflammatory and immunological regulating genes, such as Bf, C2, and C4 genes, and is situated in the middle MHC region between beta and delta blocks containing HLA-B and -C and HLA-DQ and -DR antigens, respectively. Mismatches in the c.2918+98G, c.3316C, and GB block SNPs were linked to a higher risk of grade III–IV aGVHD, according to a single-center analysis. We looked at how outcomes following 10/10 and 9/10 URD HCT were affected by GB SNP (GBS) mismatches (n = 714). The main consequence was acute GVHD. Overall survival, disease-free survival, death from transplants, recurrence, and chronic engraftment were examined as well. Using the Illumina NGS platform, 338 SNPs were located over 20 kb to GBS genotype DNA samples. The overall incidence of aGVHD grade II-IV and II-IV was 41% and 17%, respectively, during the course of 100 days. At all tested GBSs, the overall rate of matching was 23%, and at the C4 SNPs, it was 81%. Both having more GBS mismatches and having more matches across all GB SNPs evaluated had no effect on the success of transplantation. Except for an unanticipated significant relationship between having two C4 SNP mismatches and a higher hazard ratio (HR) for relapse association reported in only 15 patients (HR, 3.38, 95% confidence range, 1.75 to 6.53; P), there was no association between C4 SNP mismatches and outcomes.

Keywords: Gamma block; Major histocompatibility; Complex; Single nucleotide polymorphism; Transplantation