ASSOCIATION BETWEEN HLA CLASS I, KIR GENOTYPES AND MISSING KIR LIGAND AND CLINICAL OUTCOME IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES RECEIVING HLA-IDENTICAL HSCT

Abstract

Killer cell immunoglobulin-like receptors (KIRs) are subpopulation of receptors on NK cells. The ligands for most KIRs are HLA class I. The lack of HLA ligand for KIR receptor known as missing KIR ligand plays a role in the elimination of malignant cells by a graft-versus leukemia (GVL) effect. The aim of this study was to analyze the impact of missing KIR ligand on clinical outcome. This study was a retrospective analysis in patients undergoing T-replete hematopoietic stem cell transplant from HLA-identical sibling donors. We investigated 66 patients, including 40 patients with AML, 12 patients with ALL and 14 patients with CML. The KIR genes and HLA ligands were typed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP). We found that as high as 58 patients (87.9%) had at least one missing KIR ligand, while only 8 patients (12.1%) had no missing KIR ligand. There was no significant association of 1 or more than 1 missing KIR ligand on the clinical outcome regarding relapse, GVHD, and survival. However, the 2 or more than 2 missing KIR ligands could improve patient outcome e.g., reducing relapse (p-value=0.035), particularly in the AML patients (p-value=0.033). Moreover, this model could influent clinical outcome by reducing acute GVHD (p-value=0.005). In AML patients, significant association could also be found with increased survival rate (p-value=0.018). In addition, a dose effect of missing KIR ligand could impact AML patients clinical outcome on relapse, aGVHD and survival. This result is important for the considering of KIR missing ligand in the donor selection along with HLA matching and the development of NK adoptive therapy for AML treatment.