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

Abstract

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.

Killer Cell Immunoglobulin-Like Receptor–Ligand Mismatch in Donor versus Recipient Direction Provides Better Graft-versus-Tumor Effect in Patients with Hematologic Malignancies Undergoing Allogeneic T Cell–Replete Haploidentical Transplantation Followed by Post-Transplant Cyclophosphamide

“…Recently, Bastos-Oreiro et al [22] observed a significant impact of NK alloreactivity in patients with Hodgkin lymphoma, supporting the results initially observed in AML. In stark contrast with these results, worse outcome after T cellreplete Haplo-SCT was observed in the presence of unidirectional GVH KIR-Lmm when an antithymocyte globulin-based platform was used instead of PT-Cy [23,24].…”

Patients Lacking a KIR-Ligand of HLA Group C1 or C2 Have a Better Outcome after Umbilical Cord Blood Transplantation

“…However, the patients in these studies were not homogeneous and in addition, they used double unit UCBT and only part of them received ATG (37, 38). Our study concurs with the results of other authors because it underlines the importance of KIR-mediated NK alloreactivity in UCBT (8, 9, 25). It may be possible that the in vivo T-cell depletion of donor and patient secondary to ATG administration contributed to posttransplant expansion of functional NK cells and facilitated alloreactivity in the presence of a KIR-ligand incompatibility.…”

“…The absence of an HLA-ligand in the patient and the presence of the corresponding inhibitory KIR in the donor generate a potential NK alloreactivity against the patient target cells, resulting in alloreactivity in the graft-vs.-host (GVH) direction. Conversely, the presence of an epitope of HLA ligand for KIR in the patient and its absence in the donor will result in alloreactivity in the rejection direction (8, 9). …”

Donor selection for haploidentical hematopoietic cell transplantation‐ practice guidance

“…In the TCR haplo‐HCT protocol using PTCy, receptor‐ligand KIR‐mismatch was associated with improved survival and decrease relapse . Solomon et al suggested selecting donors with KIR recipient‐ligand mismatches and the KIR B/x 2DS2 haplotype .…”