Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation

Biol Blood Marrow Transplant. 2016 Sep;22(9):1602-1607. doi: 10.1016/j.bbmt.2016.05.016. Epub 2016 May 21.

Abstract

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.

Keywords: Allogeneic transplantation; Genotype; Killer immunoglobulin-like receptor; Natural killer (NK) cells; Non-Hodgkin lymphoma.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Bone Marrow Transplantation / methods
  • Bone Marrow Transplantation / mortality
  • Disease-Free Survival
  • Female
  • Genotype*
  • HLA Antigens
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Histocompatibility
  • Humans
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / methods
  • Peripheral Blood Stem Cell Transplantation / mortality
  • Receptors, KIR / genetics*
  • Transplantation Conditioning / methods
  • Transplantation Conditioning / mortality
  • Unrelated Donors
  • Young Adult

Substances

  • HLA Antigens
  • Receptors, KIR