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Activating killer‐cell immunoglobulin‐like receptor haplotype influences clinical outcome following HLA‐matched sibling haematopoietic stem cell transplantation

Citation

Heatley, SL and Mullighan, CG and Doherty, K and Danner, S and O'Connor, GM and Hahn, U and Szer, J and Schwarer, A and Bradstock, K and Sullivan, LC and Bardy, PG and Brooks, AG, Activating killer‐cell immunoglobulin‐like receptor haplotype influences clinical outcome following HLA‐matched sibling haematopoietic stem cell transplantation, HLA, 92, (2) pp. 74-82. ISSN 2059-2302 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 John Wiley & Sons

DOI: doi:10.1111/tan.13327

Abstract

Natural killer cells are thought to influence the outcome of hematopoietic stem cell transplant (HSCT), impacting on relapse, overall survival, graft versus host disease and the control of infection, in part through the complex interplay between the large and genetically diverse killer immunoglobulin-like receptor (KIR) family and their ligands. This study examined the relationship between KIR gene content and clinical outcomes including the control of opportunistic infections such as cytomegalovirus in the setting of human leucocyte antigen (HLA)-matched sibling HSCT in an Australian cohort. The presence of the KIR B haplotype which contain more activating receptors in the donor, in particular centromeric B haplotype genes (Cen-B), was associated with improved overall survival of patients with acute myeloid leukemia (AML) undergoing sibling HSCT and receiving myeloablative conditioning. Donor Cen-B haplotype was also associated with reduced acute graft versus host disease grades II-IV whereas donor telomeric-B haplotype was associated with decreased incidence of CMV reactivation. In contrast, we were not able to demonstrate a reduced rate of relapse when the donor had KIR Cen-B, however relapse with a donor Cen-A haplotype was a competing risk factor to poor overall survival. Here we show that the presence of donor activating KIR led to improved outcome for the patient, potentially through reduced relapse rates and decreased incidence of acute GvHD translating to improved overall survival.

Item Details

Item Type:Refereed Article
Keywords:B haplotype, KIR, natural killer cells, sibling HSCT
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Doherty, K (Dr Kathleen Doherty)
ID Code:127924
Year Published:2018
Web of Science® Times Cited:5
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2018-08-22
Last Modified:2019-04-01
Downloads:0

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