HLA Class III Variation and SNP-Based Risk Stratification in Haploidentical HCT
Petersdorf EW, McKallor C, Malkki M, et al. Extended HLA Haplotypes and Transplant Survival. Blood. 2026; (doi: 10.1182/blood.2025033031).
An understanding of extended HLA haplotypes can help narrow down the best choice of haploidentical donor for hematopoietic cell transplantation (HCT), according to results from a multivariable regression analysis. Extended HLA haplotypes are proxies for single-nucleotide polymorphisms (SNP) that drive outcomes, including relapse and mortality, following haploidentical HCT. In particular, researchers say greater insight into functional HLA class III variation is needed to curtail the risk of death after transplantation. Their analysis included 26 candidate class III SNPs, one of which proved especially informative for mortality and relapse in 1,436 patients. The SNP, rs915654, was included in three-marker haplotypes that also consisted of one class I locus and one class II locus. Fewer numbers of favorable patient and donor markers increased the risk of post-transplant mortality and relapse, while the presence of unfavorable markers correlated to increased non-relapse mortality. Knowing the implications for poor outcomes based on donor HLA haplotypes has the potential to optimize donor selection, the researchers conclude.