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

Potter, Michael N.; Wilson, Marie C.; Pearce, Rachel M.; Lee, Julia; Garcia-Sepulveda, Christian A.; Bloor, Adrian J.; Roberts, Chrissy H.; Shaw, Bronwen E.; McQuaker, I. Grant; Weisdorf, Daniel J.; Miller, Jeffrey S.; Cooley, Sarah A.; Potter, Victoria T.; Szydlo, Richard M.; Madrigal, J. Alejandro; Mayor, Neema P.; Bultitude, Will P.; Marsh, Steven G. E.; Schellekens, Jennifer; Anthias, Chloe; Orchard, Kim; Tholouli, Eleni; Malladi, Ram; Patel, Amit; MacKinnon, Stephen; Russell, Nigel H.; Byrne, Jenny L.

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.

Citation

Potter, M. N., Wilson, M. C., Pearce, R. M., Lee, J., Garcia-Sepulveda, C. A., Bloor, A. J., …Byrne, J. L. (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, 55, 1975–1984. https://doi.org/10.1038/s41409-020-0858-9

• Journal Article Type: Article
• Acceptance Date: Mar 2, 2020
• Online Publication Date: Mar 13, 2020
• Publication Date: 2020-10
• Deposit Date: Mar 6, 2020
• Publicly Available Date: Sep 14, 2020
• Journal: Bone Marrow Transplantation
• Print ISSN: 0268-3369
• Electronic ISSN: 1476-5365
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 55
• Pages: 1975–1984
• DOI: https://doi.org/10.1038/s41409-020-0858-9
• Keywords: Transplantation; Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/4095129
• Publisher URL: https://www.nature.com/articles/s41409-020-0858-9
• Additional Information: Received: 24 September 2019; Revised: 29 February 2020; Accepted: 2 March 2020; First Online: 13 March 2020; : ; : The authors declare that they have no conflict of interest.