The Pattern of KIR Ligands in Adult Patients with AML Is Associated with Various Post-Transplant Complications, Including GvHD after HLA-Matched Sibling or Unrelated Donor Transplantation

The function of natural killer (NK) cells in allogeneic stem cell transplantation (allo-SCT) is known. HLA-Cw is predominantly involved in inhibiting and activating human NK cells. Many pilot studies have examined the treatment of high-risk AML patients in terms of killer cell immunoglobulin-like receptor (KIR) disparity. NK alloreactivity may be determined by KIR and their ligands. We evaluated 370 adult AML patients scheduled for allo-SCT from family or unrelated donors. All but 41 patients in this study were in first complete remission (CR), as assessed just before the elective SCT. The HLA data for each transplant pair and clinical outcome were analyzed to study the impact of KIR ligands, especially on graft-versus-host disease (GvHD). High-resolution HLA typing was performed in 185 cases and serological data were used for the others. SCT was from an unrelated donor in 113 patients. Interestingly, we found a predominant pattern of group 1 (C1 epitope) HLA-Cw antigen in Korean acute myelogenous leukemia (AML). Only 3% of the pairs studied were C2 homozygotes. Heterozygosity of HLA-Cw C1 or C2 in either donors or recipients was closely related to the development of acute GvHD (P=0.006) and a lower rate of relapse (P=0.015). As in previous studies, we found discrepant results between the ligand-ligand model and the receptor-ligand model in the context of GvHD directed by allogeneic NK cells. We suggest that KIR ligands in allo-SCT, even in HLA-matched siblings or unrelated donors, are unique and a stable parameter to be considered in association with various post-transplant complications. According to the HLA immunogenetic background, KIR ligands are responsible for GvHD. Further investigations with longer follow-up are needed to verify the role of KIR receptor-ligand balance.