Inhibitory killer cell immunoglobulin-like receptor (iKIR) mismatches improve survival after T-cell-repleted haploidentical transplantation

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.