Faculty Collaboration Database

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

Date

05/12/2015

Pubmed ID

25960307

Pubmed Central ID

PMC4537837

DOI

10.1016/j.bbmt.2015.05.002

Scopus ID

2-s2.0-84938960931 (requires institutional sign-in at Scopus site)   35 Citations

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.

Author List

Sobecks RM, Wang T, Askar M, Gallagher MM, Haagenson M, Spellman S, Fernandez-Vina M, Malmberg KJ, Müller C, Battiwalla M, Gajewski J, Verneris MR, Ringdén O, Marino S, Davies S, Dehn J, Bornhäuser M, Inamoto Y, Woolfrey A, Shaw P, Pollack M, Weisdorf D, Milller J, Hurley C, Lee SJ, Hsu K

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Disease-Free Survival
Female
Genotype
Graft vs Host Disease
HLA-C Antigens
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Myelodysplastic Syndromes
Receptors, KIR2DL1
Retrospective Studies
Survival Rate
Transplantation Conditioning