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Alloreactivity triggered by interaction between killer cell immunoglobulin-like receptors ( KIRs) and natural killer ( NK) cells plays a role in the graft-versus-tumor effect after hematopoietic stem cell transplantation ( SCT). Our aim in this study was to evaluate this role in the setting of T-cell-repleted haploidentical SCT with postinfusion high-dose cyclophosphamide ( PT-Cy). We included 33 patients. Among patient-donor pairs with at least 1 inhibitory KIR ( iKIR) gene mismatch, event-free survival ( EFS) and cumulative incidence of relapse 1 year after transplant were significantly better (85% vs. 37% [ P = 0.008] and 18% vs. 46% [ P = 0.041], respectively). A subanalysis in 12 patients with Hodgkin's lymphoma ( HL) showed an improvement in EFS 1 year after transplant in those patients with KIR ligand mismatch (100% vs. 25%, P = 0.012), although overall survival ( OS) was not affected (85% vs. 80%, P = 0.2). Eight of 12 patient-donors pairs presented iKIR mismatches. Of note, this outcome was better in the small subgroup, both for EFS (100% vs. 25%, P = 0.012) and for OS (100% vs. 37%, P = 0.004). Our data suggest that in the setting of T-cell-repleted haploidentical SCT with PT-Cy, iKIR mismatch is associated with improved survival, with particularly good results for both iKIR and KIR ligand mismatches in patients with HL. [ABSTRACT FROM AUTHOR]