1 research outputs found
Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients
The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic
stem cell transplantation (HSCT) has not been extensively investigated. To
this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in
order to study the effect of HLA-E as a natural killer (NK)-alloreactivity
mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival
(OS), disease free survival (DFS), relapse incidence (RI) and non-relapse
mortality (NRM) were set as endpoints. Analysis of our data revealed a
significant correlation between HLA-E mismatch and improved HSCT outcome, as
shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate
(hazard ratio (HR)=0.63, confidence interval (CI) 95%=0.48–0.83, P=0.001)
analyses. Further subgroup analysis demonstrated that the positive effect of
HLA-E mismatch was significant and pronounced in advanced disease patients
(n=120) (5-year OS: 50% vs. 18%, P=0.005; HR=0.40, CI 95%=0.22–0.72, P=0.002;
results from univariate and multivariate analyses, respectively). The study
herein is the first to report an association between HLA-E incompatibility and
improved post–transplant prognosis in AL patients who have undergone matched
unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account
for the better outcomes observed. Notwithstanding the necessity for in vitro
and confirmational studies, our findings highlight the clinical relevance of
HLA-E matching and strongly support prospective HLA-E screening upon donor
selection for matched AL unrelated HSCTs