Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell–replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA–matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P =.05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P =.007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR],.63, P =.02) and improved PFS (RR,.71, P =.008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA–matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation.
Bibliographical noteFunding Information:
Research reported in this publication was supported by the National Center for Advancing Translational Sciences and the National Institutes of Health (NIH) Award Number UL1TR000114 (V.B.) and National Cancer Institute P01 111412 (D.J.W., T.W., S.G.E.M., E.T., M.H., S.R.S., L.A.G., M.L., P.P., J.S.M., S.C.). This work was supported in part by NIH P30 CA77598 utilizing the Masonic Cancer Center, University of Minnesota Oncology Medical Informatics and Services shared resource. The Center for International Blood and Marrow Transplant Research (T.W., M.H., and S.R.S.) is supported by Public Health Service grant/cooperative agreement U24-CA076518 from the National Cancer Institute (NCI) , the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) ; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS) ; 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research ; and others. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government.
© 2016 American Society for Blood and Marrow Transplantation
- Allogeneic transplantation
- Killer immunoglobulin-like receptor
- Natural killer (NK) cells
- Non-Hodgkin lymphoma