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

Biol Blood Marrow Transplant. 2018 Mar;24(3):549-554. doi: 10.1016/j.bbmt.2017.11.042. Epub 2017 Dec 13.

Abstract

We evaluated the impact of unidirectional donor versus recipient killer cell immunoglobulin-like receptor (KIR)-ligand mismatch (KIR-Lmm) on the outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a cohort of 144 patients treated for various hematologi diseases. We separately analyzed 81 patients in complete remission (CR group) and 63 with active disease (no CR group) at the time of Haplo-SCT. One-third of patients in each group had KIR-Lmm. In the no CR group, KIR-Lmm was associated with a significantly lower incidence of relapse (hazard ratio, .21; P = .013) and better progression-free survival (hazard ratio, .42; P = .028), with no significant increase in graft-versus-host disease incidence or nonrelapse mortality. In contrast, in the CR group no benefit of KIR-Lmm was observed. Our results encourage considering KIR-Lmm as an additional tool to improve donor selection for T cell-replete Haplo-SCT with PT-Cy, especially in patients with high-risk diseases.

Keywords: Graft-versus-leukemia effect; Killer cell immunoglobulin-like receptor; Natural killer cells; T cell–replete haploidentical stem cell transplantation.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Cyclophosphamide / administration & dosage*
  • Disease-Free Survival
  • Female
  • Graft vs Tumor Effect / immunology*
  • Hematologic Neoplasms* / immunology
  • Hematologic Neoplasms* / mortality
  • Hematologic Neoplasms* / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • Receptors, KIR / immunology*
  • Survival Rate

Substances

  • Receptors, KIR
  • Cyclophosphamide