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

被引:10
作者
Bultitude, Will P. [1 ,2 ]
Schellekens, Jennifer [1 ,2 ]
Szydlo, Richard M. [1 ,3 ]
Anthias, Chloe [1 ,4 ]
Cooley, Sarah A. [5 ]
Miller, Jeffrey S. [6 ]
Weisdorf, Daniel J. [6 ]
Shaw, Bronwen E. [7 ,8 ]
Roberts, Chrissy H. [9 ]
Garcia-Sepulveda, Christian A. [10 ]
Lee, Julia [11 ]
Pearce, Rachel M. [11 ]
Wilsonm, Marie C. [1 ,11 ]
Potter, Michael N. [4 ]
Byrne, Jenny L. [12 ]
Russell, Nigel H. [12 ]
MacKinnon, Stephen [13 ]
Bloor, Adrian J. [14 ]
Patel, Amit [15 ]
McQuaker, I. Grant [16 ]
Malladi, Ram [17 ]
Tholouli, Eleni [18 ]
Orchard, Kim [19 ]
Potter, Victoria T. [20 ]
Madrigal, J. Alejandro [1 ,2 ]
Mayor, Neema P. [1 ,2 ]
Marsh, Steven G. E. [1 ,2 ]
机构
[1] Royal Free Hosp, Anthony Nolan Res Inst, London, England
[2] UCL, Canc Inst, Royal Free Campus, London, England
[3] Imperial Coll London, London, England
[4] Royal Marsden Hosp, Surrey, England
[5] Fate Therapeut, San Diego, CA USA
[6] Univ Minnesota, Haematol Oncol & Transplantat, Minneapolis, MN USA
[7] CIBMTR, Milwaukee, WI USA
[8] Froedtert & Med Coll Wisconsin Clin Canc Ctr, Milwaukee, WI USA
[9] London Sch Hyg & Trop Med, London, England
[10] Univ Autonoma San Luis Potosi, Fac Med, Lab Genom Viral & Humana, San Luis Potosi, San Luis Potosi, Mexico
[11] Guys Hosp, British Soc Blood & Marrow Transplantat & Cellula, London, England
[12] Nottingham Univ Hosp, Nottingham, England
[13] Univ Coll London Hosp NHS Fdn Trust, London, England
[14] Christie NHS Fdn Trust, Manchester, Lancs, England
[15] Liverpool Univ Hosp, Liverpool, Merseyside, England
[16] Gartnavel Royal Hosp, West Scotland Canc Ctr, Glasgow, Lanark, Scotland
[17] Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England
[18] Manchester Univ NHS Fdn Trust, Manchester, Lancs, England
[19] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England
[20] Kings Coll Hosp London, London, England
基金
美国国家卫生研究院;
关键词
NATURAL-KILLER-CELLS; UNRELATED TRANSPLANTATION; CLINICAL-OUTCOMES; SUPERIOR SURVIVAL; LIGAND MISMATCH; RECEPTOR GENES; ALLOREACTIVITY; RELAPSE; IMPACT; HAPLOTYPES;
D O I
10.1038/s41409-020-0858-9
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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.
引用
收藏
页码:1975 / 1984
页数:10
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