Negative Impact of Unidirectional Host-versus-Graft Killer Cell Immunoglobulin-like Receptor Ligand Mismatch on Transplantation Outcomes after Unmanipulated Haploidentical Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia.

Abstract

This study explored the influence of mismatched inhibitory killer cell immunoglobulin-like receptor (KIR) ligands on the outcome of haploidentical transplantation using T cell-replete, granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in adult patients with acute myeloid leukemia (AML). Three groups were examined: unidirectional graft-versus-host KIR ligand mismatched (GVH-KIR-MM; n= 33), bidirectional KIR ligand matched (KIR-M; n= 41), and unidirectional host-versus-graft KIR ligand mismatched (HVG-KIR-MM; n= 26). All recipients were treated with the same conditioning regimen (800 cGy total body irradiation, fludarabine, busulfan, and antithymocyte globulin). After a median follow-up of 26 months, the 2-year cumulative incidence of relapse was significantly higher in HVG-KIR-MM (40.3% ± 10.3%) versus others (18.9% ± 4.8%, P= .044). In the standard-risk group, the 2-year disease-free survival (DFS) was significantly lower in HVG-KIR-MM (51.8% ± 11.2%) compared with GVH-KIR-MM (88% ± 8.1%, P= .025). Multivariate analysis showed that HVG-KIR-MM was significantly associated with higher relapse (hazard ratio [HR], 10.7; P= .002) and lower DFS (HR, 3.4; P= .012). Subgroup analysis revealed increased DFS with higher doses of CD3(+)CD8(+) and CD3(-)CD56(+) grafts in GVH-KIR-MM (90.9% ± 8.7%, P= .006); there was no such effect in the other groups. Although our conclusions are limited by the absence of donor KIR genotype data, our study suggests unidirectional KIR ligand incompatibility in the host-versus-graft vector has a detrimental effect on T cell-replete haploidentical transplantation outcomes in adult patients with AML.