Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation

Biol Blood Marrow Transplant. 2015 Sep;21(9):1589-96. doi: 10.1016/j.bbmt.2015.05.002. Epub 2015 May 8.

Abstract

Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2(+) patients. AML patients with KIR2DS1(+), HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.

Keywords: AML/MDS; Killer immunoglobulin-like receptor (KIR); Reduced-intensity conditioning HCT.

Publication types

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

MeSH terms

  • Adult
  • Disease-Free Survival
  • Female
  • Genotype*
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control
  • HLA-C Antigens / genetics*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / mortality
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / mortality
  • Myelodysplastic Syndromes* / therapy
  • Receptors, KIR2DL1 / genetics*
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning*

Substances

  • HLA-C Antigens
  • HLA-C*02 antigen
  • KIR2DL1 protein, human
  • Receptors, KIR2DL1