TY  - JOUR
A1  - Tsamadou, Chrysanthi
A1  - Fürst, Daniel
A1  - Vucinic, Vladan
A1  - Bunjes, Donald
A1  - Neuchel, Christine
A1  - Mytilineos, Daphne
A1  - Gramatzki, Martin
A1  - Arnold, Renate
A1  - Wagner, Eva Maria
A1  - Einsele, Hermann
A1  - Müller, Carlheinz
A1  - Schrezenmeier, Hubert
A1  - Mytilineos, Joannis
T1  - Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients
JF  - Haematologica
N2  - 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.
KW  - medicine
KW  - acute leukemia (AL)
KW  - hematopoietic stem cell transplantation (HSCT)
KW  - human leukocyte antigen-E (HLA-E)
KW  - HLA-E matching
KW  - HSTC outcome
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173325
VL  - 102
IS  - 11
ER  -