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

Biol Blood Marrow Transplant. 2019 Dec;25(12):2357-2365. doi: 10.1016/j.bbmt.2019.08.007. Epub 2019 Aug 16.

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 Center for International Blood and Marrow Transplant Research data and samples of 1840 adult patients with acute leukemia 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 .01. D/R HLA-E genotype analysis revealed a significant association of donor HLA-E*01:03/01:03 genotype with DFS (hazard ratio [HR] = 1.35, P = .0006) and TRM (HR = 1.41, P = .0058) in patients who received T cell replete (ie, without in vivo T cell depletion) transplants (n = 1297). As for 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.

Keywords: Acute Leukemia; DFS; Donor HLA-E; In vivo T cell depletion; TRM; Unrelated HSCT.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Disease-Free Survival
  • Female
  • HLA-E Antigens
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Antigens Class I* / genetics
  • Histocompatibility Antigens Class I* / immunology
  • Humans
  • Leukemia* / genetics
  • Leukemia* / immunology
  • Leukemia* / mortality
  • Leukemia* / therapy
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • Survival Rate
  • Unrelated Donors*

Substances

  • Histocompatibility Antigens Class I