Donor HLA-E Status Associates with Disease-Free Survival and Transplant-Related Mortality after Non In Vivo T Cell-Depleted HSCT for Acute Leukemia

Abstract Previous studies have suggested that HLA-E may have a significant role in the outcome of matched unrelated hematopoietic stem cell transplantation (HSCT) especially for patients with acute leukemia. We used CIBMTR data and samples of 1840 adult acute leukemia patients and their 10/10 HLA-matched unrelated donors to investigate the impact of HLA-E matching status as well as of donor/recipient (D/R) HLA-E genotype on post-HSCT outcome. Both, patients and donors were HLA-E genotyped by next generation sequencing. All patients received their first transplant in complete remission between 2000 and 2015. Median follow-up time was 90 months. Overall survival, disease free survival (DFS), transplant-related mortality (TRM) and relapse incidence were primary endpoints with statistical significance set at 0.01. D/R HLA-E genotype analysis revealed a significant association of donor HLA-E*01:03/01:03 genotype with DFS (HR=1.35, p=0.0006) and TRM (HR=1.41, p=0.0058) in patients who received T-cell replete (i.e. without in vivo T-cell depletion) transplants (n=1297). As to D/R HLA-E matching, we did not identify any significant effect on any of the clinical outcome endpoints. In conclusion, this is the largest study to date reporting an improvement of DFS and TRM after matched unrelated HSCT by avoidance of HLA-E*01:03 homozygous donors in patients transplanted with T-cell replete grafts for acute leukemia.