Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission

J Tanaka,Y Kanda,T Yabe,K Oba,K Miyamura,H Ogawa,S Takahashi,K Kato,Y Takahashi,Y Morishima,H Kanamori,S Kato,S Taniguchi,Y Onishi,N Aotsuka,Y Atsuta

doi:10.1038/bcj.2013.62

Abstract

To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand incompatibility on outcomes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in complete remission after single cord blood transplantation (CBT), we assessed the outcomes of CBT registered in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of 643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized according to their KIR ligand incompatibility by determining whether or not they expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient–donor pairs were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139 patient–donor pairs were incompatible in the host-versus-graft (HVG) direction. Univariate and multivariate analyses showed no significant differences between the KIR ligand-incompatible and compatible groups in the GVH direction for both AML and ALL patients of overall survival, disease-free survival, relapse incidence, non-relapse mortality and acute GVH disease. However, KIR incompatibility in the HVG direction ameliorated engraftment in ALL patients (hazard ratio 0.66, 95% confidence interval 0.47–0.91, P=0.013). Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. However, it is necessary to pay attention to KIR incompatibility in the HVG direction for engraftment.

Highlights

Killer cell immunoglobulin-like receptor (KIR) ligand incompatibility may have some important roles in transplantation outcomes such as leukemia relapse and leukemia-free survival.[1,2,3,4] Ruggeri et al.[5,6] reported surprisingly good clinical results that indicated no relapse, no rejection and no acute graft-versus-host disease (GVHD) after human leukocyte antigen (HLA) haplotypemismatched transplantations with killer cell immunoglobulin-like receptor (KIR) ligand incompatibility in the GVH direction for acute myeloid leukemia (AML) patients
There were no significant differences in overall survival (OS), disease-free survival (DFS), relapse incidence, non-relapse mortality (NRM), engraftment and acute GVHD between the KIR
The role of KIR ligand incompatibility in allo SCT is controversial with various diseases and conditionings.[16,17]

Summary

INTRODUCTION

Killer cell immunoglobulin-like receptor (KIR) ligand incompatibility may have some important roles in transplantation outcomes such as leukemia relapse and leukemia-free survival.[1,2,3,4] Ruggeri et al.[5,6] reported surprisingly good clinical results that indicated no relapse, no rejection and no acute graft-versus-host disease (GVHD) after human leukocyte antigen (HLA) haplotypemismatched transplantations with KIR ligand incompatibility in the GVH direction for acute myeloid leukemia (AML) patients. They reported that donor allogeneic natural killer (NK) cells attacked host antigen-presenting cells (APCs), resulting in the suppression of GVHD.

Transplant procedures

RESULTS

DISCUSSION