Donor Selection Based on Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype May Improve Outcome After T-Cell-Replete Haploidentical Transplantation

Transplant Proc. 2018 Mar;50(2):679-682. doi: 10.1016/j.transproceed.2017.09.070.

Abstract

Background: In haploidentical stem cell transplantation (SCT), the "ideal donor" selection is not performed in a standardized way according to killer cell immunoglobulin-like receptor (KIR) genotype expressed by potential donors. The aim of this study was to evaluate the relevance of KIR genotype in a series of patients submitted to haploidentical SCT in our center.

Methods: We retrospectively analyzed 30 patients that were prepared with the use of a conditioning regimen including thiotepa-busulfan-fludarabine with high doses of post-transplantation cyclophosphamide (CyPT) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis. We analyzed the impact of the KIR genotype variables (donor AA/Bx haplotype, donor B content, KIR inhibitor mismatches, and mismatching in KIR ligands in the graft-versus-host direction and the host-versus-graft direction) on overall survival, GVHD-free survival, and event-free survival.

Results: Statistical significance was found for the presence of mismatches on KIR ligands in the graft-versus-host direction in relation to the diagnosis of chronic GVHD (54% vs 100%; P = .004). Significance was also found for the effect of the donor presence AA or Bx haplotype in relation to the diagnosis of chronic GVHD (50% vs 86%; P = .033).

Conclusions: KIR genotyping can provide useful information that can help us with the right donor choice for haploidentical SCT without T-cell depletion with high doses of CyPT. Donors with Bx haplotype that do not show KIR ligand incompatibilities in the graft-versus-host direction may provide a lower risk of GVHD.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Donor Selection / methods*
  • Female
  • Genotype
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Receptors, KIR / genetics*
  • Retrospective Studies
  • T-Lymphocytes / immunology
  • Transplantation Conditioning
  • Transplantation, Haploidentical / methods*
  • Young Adult

Substances

  • Receptors, KIR