KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL.

We analyzed the influence of donor killer-cell immunoglobulin-like receptor (KIR) gene haplotypes on the risk for relapse and the probability of event-free survival (EFS) in children with acute lymphoblastic leukemia who received human leukocyte antigen-haploidentical transplantation of ex vivo T-cell-depleted peripheral blood stem cells. The KIR gene haplotype was evaluated in 85 donors, and the KIR B content score was determined in the 63 KIR haplotype B donors. Patients transplanted from a KIR haplotype B donor had a significantly better EFS than those transplanted from a KIR haplotype A donor (50.6% vs 29.5%, respectively; P = .033). Moreover, a high donor KIR B-content score was associated with a significantly reduced risk for relapse (Log-rank test for trend, P = .026). These data indicate that KIR genotyping should be included in the donor selection algorithm for haploidentical transplantation in children with acute lymphoblastic leukemia with the aim of choosing, whenever possible, a KIR haplotype B donor with a high KIR B-content score.

KIR haplotype B donors but not KIR-ligand mismatch result in a reduced incidence of relapse after haploidentical transplantation using reduced intensity conditioning and CD3/CD19-depleted grafts.

Natural killer (NK)-cell alloreactivity after allogeneic hematopoietic cell transplantation (HCT) is influenced by the interaction of killer-cell immunoglobulin-like receptors (KIRs) on donor NK cells and human leukocyte antigen (HLA) class I ligands on recipient cells. We investigated the influence of donor KIR haplotype and KIR-ligand mismatch (MM) on relapse in 57 patients with hematologic malignancies receiving haploidentical HCT after reduced intensity conditioning and graft CD3/CD19 depletion. Of the 57 donors, 17 had KIR haplotype A (29.8 %) and 40 had KIR haplotype B (70.2 %). A KIR-ligand MM was found in 34 of 57 patients (59.6 %). There was no difference between donor KIR haplotypes in non-relapse mortality (NRM, p = 0.200) but had a significantly reduced incidence of relapse for patients with a haplotype B donor (p = 0.001). In particular, patients in partial remission (PR) benefited more from a haplotype B graft (p = 0.008) than patients in complete remission (CR, p = 0.297). Evaluating KIR-ligand MM cumulative incidences of relapse (p = 0.680) or NRM (p = 0.579), we found no significant difference. In conclusion, in the setting of reduced intensity conditioning (RIC) and CD3/CD19-depleted haploidentical HCT, we could not confirm the positive data with KIR-ligand MM but observed a significant lower risk of relapse with a KIR haplotype B donor.