Donor HLA-E*01:06 Confers Protection from Relapse and Improved Survival after T-Cell Depleted Matched Unrelated Donor...

Hematopoietic cell transplantation (HCT) is the gold standard curative therapy for many hematological malignancies, but disease relapse is common and the primary cause of treatment failure. While the impact of matching the classical HLA loci on HCT outcomes is known, the role of the non-classical HLA class I gene HLA-E is unclear but has been limited to HLA-E*01:01/01:03 thus far. The aims of this study were to genotype the full length of HLA-E for a cohort of UK HCT patients and unrelated donors, to enable investigation of all HLA-E alleles and use this full-length genotyping to investigate any statistical associations of HLA-E matching or genotype with UK HCT patient clinical outcomes. To investigate this, we retrospectively genotyped 1878 UK patients with hematological malignancies and their matched unrelated donors for HLA-E at a definitive allele resolution and analyzed patient outcomes with respect to the HLA-E genetic data using adjusted multivariate analysis models. Multivariate analysis showed that the presence of the allele HLA-E*01:06 in the donor genotype was associated with significantly reduced 5-yr risk of relapse (hazard ratio [HR] = 0.39; P = .002) and increased progression-free and overall survival (HR = 0.59; P = .003 and HR = 0.69; P = .04). We also observed a detrimental impact of the allele HLA-E*01:03:05 in the donor genotype on relapse risk (HR = 2.54; P = .001) and progression-free survival (HR = 1.90; P = .006), compared with donors without this allele. Our data show a potential role for HLA-E in unrelated donor HCT, where donor HLA-E genotypes appear to correlate with patient relapse rates and patient survival. This is the first study to investigate the impact of HLA-E on HCT outcomes using a full-length genotyping strategy, which allowed us to identify potential correlations from alleles beyond HLA-E*01:01/01:03 for the first time.