Since relapse following allogeneic hematopoietic stem cell transplantation (HSCT) can be due to the escape of the residual malignant cells from the graft- versus-leukemia (GvL) effect and given the role of NK cells in GvL and the importance of HLA-E in the modulation of NK cell function, we investigated whether polymorphisms of HLA-E molecule could impact on the incidence of relapse and the improvement of Disease-free Survival (DFS) after allogeneic HSCT. The study group included 56 pairs of donors and patients with malignant hematological disorders undergoing HLA-E matched allogeneic HSCT. The median follow-up was 43.6 (range 20.5-113.1) months. They were genotyped for HLA-E locus using a sequence-specific primer (SSP)-PCR. We found a lower incidence of relapse (p= 0.02) in the patients with HLA-E* 0103/0103 genotype compared to those with other genotypes of HLA-E. We also showed an association between HLA-E* 0103/0103 genotype and a better DFS (p= 0.001). Our results suggest a protective role for HLA-E* 0103/0103 genotype against relapse and an association between this genotype and an improved DFS following HLA-E matched allogeneic HSCT. ? 2013 Elsevier Ltd.