Presence of donor-encoded centromeric KIR B content increases the risk of infectious mortality in recipients of myeloablative, T-cell deplete, HLA-matched HCT to treat AML.

Bultitude, Will P and Schellekens, Jennifer and Szydlo, Richard M and Anthias, Chloe and Cooley, Sarah A and Miller, Jeffrey S and Weisdorf, Daniel J and Shaw, Bronwen E and Roberts, Chrissy H and Garcia-Sepulveda, Christian A and Lee, Julia and Pearce, Rachel M and Wilson, Marie C and Potter, Michael N and Byrne, Jenny L and Russell, Nigel H and MacKinnon, Stephen and Bloor, Adrian J and Patel, Amit and McQuaker, I Grant and Malladi, Ram and Tholouli, Eleni and Orchard, Kim and Potter, Victoria T and Madrigal, J Alejandro and Mayor, Neema P and Marsh, Steven G E (2020) Presence of donor-encoded centromeric KIR B content increases the risk of infectious mortality in recipients of myeloablative, T-cell deplete, HLA-matched HCT to treat AML. Bone marrow transplantation. ISSN 1476-5365.

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Official URL: https://www.nature.com/articles/s41409-020-0858-9

Abstract

The reported influence of donor Killer-cell Immunoglobulin-like Receptor (KIR) genes on the outcomes of haematopoietic cell transplantation (HCT) are contradictory, in part due to diversity of disease, donor sources, era and conditioning regimens within and between different studies. Here, we describe the results of a retrospective clinical analysis establishing the effect of donor KIR motifs on the outcomes of 119 HLA-matched, unrelated donor HCT for adult acute myeloid leukaemia (AML) using myeloablative conditioning (MAC) in a predominantly T-cell deplete (TCD) cohort. We observed that HCT involving donors with at least one KIR B haplotype were more likely to result in non-relapse mortality (NRM) than HCT involving donors with two KIR A haplotypes (p = 0.019). Upon separation of KIR haplotypes into their centromeric (Cen) and telomeric (Tel) motif structures, we demonstrated that the Cen-B motif was largely responsible for this effect (p = 0.001). When the cause of NRM was investigated further, infection was the dominant cause of death (p = 0.006). No evidence correlating donor KIR B haplotype with relapse risk was observed. The results from this analysis confirm previous findings in the unrelated, TCD, MAC transplant setting and imply a protective role for donor-encoded Cen-A motifs against infection in allogeneic HCT recipients.

Item Type: Article
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Mrs Yolande Brookes
Date Deposited: 03 Apr 2020 10:28
Last Modified: 03 Apr 2020 10:28
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2954

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