KIR Ligands and Prediction of Relapse After Unrelated Donor Hematopoietic Cell Transplantation for Hematologic Malignancy

Biol Blood Marrow Transplant. 2006 Aug;12(8):828-36. doi: 10.1016/j.bbmt.2006.04.008.

Abstract

Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval, .043-0.85; P = .004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P = .004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P = .04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P = .95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease-Free Survival
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Follow-Up Studies
  • HLA-B Antigens / genetics*
  • HLA-B Antigens / immunology
  • HLA-C Antigens / genetics
  • HLA-C Antigens / immunology
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Humans
  • Isoantigens / genetics*
  • Isoantigens / immunology
  • Killer Cells, Natural / immunology
  • Ligands
  • Living Donors*
  • Lymphocyte Transfusion* / mortality
  • Male
  • Receptors, Immunologic / agonists
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, KIR
  • Recurrence
  • Risk Factors
  • Survival Rate
  • T-Lymphocytes / immunology
  • Transplantation, Homologous

Substances

  • Epitopes
  • HLA-B Antigens
  • HLA-Bw4 antigen
  • HLA-C Antigens
  • Isoantigens
  • Ligands
  • Receptors, Immunologic
  • Receptors, KIR