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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)-alloreact...

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Detalles Bibliográficos
Autores principales: Tsamadou, Chrysanthi, Fürst, Daniel, Vucinic, Vladan, Bunjes, Donald, Neuchel, Christine, Mytilineos, Daphne, Gramatzki, Martin, Arnold, Renate, Wagner, Eva Maria, Einsele, Hermann, Müller, Carlheinz, Schrezenmeier, Hubert, Mytilineos, Joannis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664399/
https://www.ncbi.nlm.nih.gov/pubmed/28883078
http://dx.doi.org/10.3324/haematol.2017.169805
Descripción
Sumario: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.