TY - JOUR
T1 - Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation
AU - Sobecks, Ronald M.
AU - Wang, Tao
AU - Askar, Medhat
AU - Gallagher, Meighan M.
AU - Haagenson, Michael
AU - Spellman, Stephen
AU - Fernandez-Vina, Marcelo
AU - Malmberg, Karl Johan
AU - Müller, Carlheinz
AU - Battiwalla, Minoo
AU - Gajewski, James
AU - Verneris, Michael R.
AU - Ringdén, Olle
AU - Marino, Susana
AU - Davies, Stella
AU - Dehn, Jason
AU - Bornhäuser, Martin
AU - Inamoto, Yoshihiro
AU - Woolfrey, Ann
AU - Shaw, Peter
AU - Pollack, Marilyn
AU - Weisdorf, Daniel
AU - Milller, Jeffrey
AU - Hurley, Carolyn
AU - Lee, Stephanie J.
AU - Hsu, Katharine
N1 - Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbmt.2015.05.002
DO - 10.1016/j.bbmt.2015.05.002
M3 - Article
C2 - 25960307
AN - SCOPUS:84938960931
SN - 1083-8791
VL - 21
SP - 1589
EP - 1596
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -