HLA and KIR genotyping correlates with relapse after T-cell-replete haploidentical transplantation in chronic myeloid leukaemia patients

Br J Cancer. 2014 Sep 9;111(6):1080-8. doi: 10.1038/bjc.2014.423. Epub 2014 Jul 31.

Abstract

Background: Conflicting results have been reported regarding the predicative roles of alloreactive natural killer (NK) cells on the outcomes of transplantation in leukaemia patients.

Methods: We prospectively analysed the human leukocyte antigen (HLA) typing of donor-recipient pairs and the KIR typing of the donors in 97 CML patients to address the predictive roles of NK cells in relapse undergoing T-cell-replete haploidentical transplantation.

Results: Patients with class I ligands for the donor-inhibitory KIR gene exhibited decreased molecular and haematologic relapse rates (P=0.003 and P=0.015, respectively). There was a significantly reduced risk of molecular and haematologic relapse in patients with HLA-C1C2 or C2C2 who accepted donors with KIR2DS1 or in patients with HLA-Bw4 who accepted donors with KIR3DS1 ('recipient with relevant KIR ligand for donor-activating KIR', n=25), compared with the remaining transplants (n=72, P=0.009 and P=0.009, respectively). In addition, the presence of class I ligand in the recipients of donor-activating KIR contributed to a decreased relapse rate in patients lacking class I ligand in the recipient of donor-inhibitory KIR (P=0.04 and P=0.03, respectively).

Conclusions: This study suggests that the presence of class I ligands for the donor-activating or donor-inhibitory KIR gene in the recipient might confer some protection against leukaemic relapse in T-cell-replete haploidentical transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Disease-Free Survival
  • Donor Selection
  • Female
  • Genotype
  • Graft vs Host Disease / etiology
  • HLA-B Antigens / genetics*
  • HLA-C Antigens / genetics*
  • Haploidy
  • Humans
  • Killer Cells, Natural / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Ligands
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, KIR / genetics*
  • Receptors, KIR3DS1 / genetics*
  • Recurrence
  • Survival Rate
  • T-Lymphocytes / transplantation*
  • Young Adult

Substances

  • HLA-B Antigens
  • HLA-Bw4 antigen
  • HLA-C Antigens
  • HLA-C*01:02 antigen
  • HLA-C*02 antigen
  • KIR2DS1 protein, human
  • Ligands
  • Receptors, KIR
  • Receptors, KIR3DS1