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Clinical Trial
. 2019 Dec;25(12):2357-2365.
doi: 10.1016/j.bbmt.2019.08.007. Epub 2019 Aug 16.

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

Chrysanthi Tsamadou  1 , Daniel Fürst  1 , Tao Wang  2 , Naya He  2 , Stephanie J Lee  3 , Stephen R Spellman  4 , Katharina Fleischhauer  5 , Katharine C Hsu  6 , Sophie Paczesny  7 , Michael R Verneris  8 , Hubert Schrezenmeier  1 , Joannis Mytilineos  9
Affiliations
Clinical Trial

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

Chrysanthi Tsamadou et al. Biol Blood Marrow Transplant. 2019 Dec.

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.

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Conflict of interest statement

DECLARATION OF COMPETING INTEREST

There are no conflicts of interest to report.

Figures

Figure 1.
Figure 1.
Joint D/R HLA-E genotype analysis and DFS. Adjusted curves of DFS probability with respect to joint D/R HLA-E genotype analysis. 01:01+, 01:01+ = donor and recipient HLA-E*01:01/01:01 and/or *01:01/01:03 (n = 1352); 01:01+, 01:03/01:03 = donor HLA-E*01:01/01:01 and/or *01:01/01:03 and recipient HLA-E*01:03/ 01:03 (n = 123); 01:03/01:03, 01:01+ = donor HLA-E*01:03/01:03 and recipient HLA-E*01:01/01:01 and/or 01:01/01:03 (n = 136); 01:03/01:03, 01:03/01:03 = donor and recipient HLA-E*01:03/01:03 (n = 195). Data on DFS rates are summarized in Table 4
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