Impact of KIR and HLA genotypes on outcomes after reduced-intensity conditioning hematopoietic cell transplantation Journal Article


Authors: Sobecks, R. M.; Wang, T.; Askar, M.; Gallagher, M. M.; Haagenson, M.; Spellman, S.; Fernandez Vina, M.; Malmberg, K. J.; Müller, C.; Battiwalla, M.; Gajewski, J.; Verneris, M. R.; 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, S. J.; Hsu, K.
Article Title: Impact of KIR and HLA genotypes on outcomes after reduced-intensity conditioning hematopoietic cell transplantation
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. © 2015 American Society for Blood and Marrow Transplantation.
Keywords: adult; cancer chemotherapy; controlled study; treatment outcome; aged; unclassified drug; major clinical study; mortality; bone marrow; genotype; hematopoietic stem cell transplantation; retrospective study; acute graft versus host disease; myelodysplastic syndrome; whole body radiation; donor; peripheral blood stem cell; acute myeloblastic leukemia; graft versus host reaction; reduced intensity conditioning; natural killer cell; killer cell immunoglobulin like receptor; hla c antigen; hla antigen; alemtuzumab; thymocyte antibody; alloimmunity; hla c2 antigen; human; male; female; article; aml/mds; killer immunoglobulin-like receptor (kir); reduced-intensity conditioning hct
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 21
Issue: 9
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2015-09-01
Start Page: 1589
End Page: 1596
Language: English
DOI: 10.1016/j.bbmt.2015.05.002
PROVIDER: scopus
PMCID: PMC4537837
PUBMED: 25960307
DOI/URL:
Notes: Export Date: 2 September 2015 -- Source: Scopus
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  1. Katharine C Hsu
    152 Hsu