Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT.

Abstract

Natural killer (NK) cells can alter the outcome of hematopoietic cell transplantation (HCT) if donor alloreactivity targets the recipient. Since most NK cells express inhibitory killer-immunoglobulin receptors (KIRs), we hypothesized that the susceptibility of recipient cells to donor NK cell-mediated lysis is genetically predetermined by the absence of known KIR ligands. We analyzed data from 2062 patients undergoing unrelated donor HCT for acute myeloid leukemia (AML; n = 556), chronic myeloid leukemia (CML; n = 1224), and myelodysplastic syndrome (MDS; n = 282). Missing 1 or more KIR ligands versus the presence of all ligands protected against relapse in patients with early myeloid leukemia (relative risk [RR] = 0.54; n = 536, 95% confidence interval [CI] 0.30-0.95, P = .03). In the subset of CML patients that received a transplant beyond 1 year from diagnosis (n = 479), missing a KIR ligand independently predicted a greater risk of developing grade 3-4 acute graft-versus-host disease (GVHD; RR = 1.58, 95% CI 1.13-2.22; P = .008). These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia.

• Authors: Jeffery S Miller, Sarah Cooley, Peter Parham, Sherif S Farag, Michael R Verneris, Karina L McQueen, Lisbeth A Guethlein, Elizabeth A Trachtenberg, Michael Haagenson, Mary M Horowitz, John P Klein, Daniel J Weisdorf
• Journal: Blood (Blood) Vol. 109 Issue 11 Pg. 5058-61 (Jun 01 2007) ISSN: 0006-4971 [Print] United States
• PMID: 17317850 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ligands
• Receptors, Immunologic
• Receptors, KIR

Topics

• Genetic Predisposition to Disease
• Graft vs Host Disease (diagnosis, metabolism)
• Humans
• Killer Cells, Natural (cytology)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, immunology)
• Leukemia, Myeloid, Acute (blood, immunology)
• Ligands
• Myelodysplastic Syndromes (blood, immunology)
• Receptors, Immunologic (chemistry, immunology)
• Receptors, KIR
• Recurrence
• Registries
• Risk
• Transplantation, Homologous (methods)
• Treatment Outcome