Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients
Tsamadou C, Fuerst D, Vucinic V, Bunjes D, Neuchel C, Mytilineos D, Gramatzki M, Arnold R, Wagner EM, Einsele H, Mueller C, Schrezenmeier H, Mytilineos J (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 102
Pages Range: 1947-1955
Journal Issue: 11
DOI: 10.3324/haematol.2017.169805
Abstract
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 HLAE screening upon donor selection for matched AL unrelated HSCTs.
Involved external institutions
Universität Ulm
Germany (DE)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Zentrales Knochenmarkspender-Register für die Bundesrepublik Deutschland gGmbH (ZKRD)
Germany (DE)
DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen
Germany (DE)
Universität Leipzig
Germany (DE)
Johannes Gutenberg-Universität Mainz (JGU)
Germany (DE)
Germany (DE)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Zentrales Knochenmarkspender-Register für die Bundesrepublik Deutschland gGmbH (ZKRD)
Germany (DE)
DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen
Germany (DE)
Universität Leipzig
Germany (DE)
Johannes Gutenberg-Universität Mainz (JGU)
Germany (DE)
How to cite
APA:
Tsamadou, C., Fuerst, D., Vucinic, V., Bunjes, D., Neuchel, C., Mytilineos, D.,... Mytilineos, J. (2017). Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients. Haematologica, 102(11), 1947-1955. https://doi.org/10.3324/haematol.2017.169805
MLA:
Tsamadou, Chrysanthi, et al. "Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients." Haematologica 102.11 (2017): 1947-1955.
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