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.
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.
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DOI：
10.1038/s41409-020-0858-9
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发表时间：
2020-10
影响因子：
4.8
通讯作者：
Marsh SGE
中科院分区：
文献类型：
--
作者：
Bultitude WP;Schellekens J;Szydlo RM;Anthias C;Cooley SA;Miller JS;Weisdorf DJ;Shaw BE;Roberts CH;Garcia-Sepulveda CA;Lee J;Pearce RM;Wilson MC;Potter MN;Byrne JL;Russell NH;MacKinnon S;Bloor AJ;Patel A;McQuaker IG;Malladi R;Tholouli E;Orchard K;Potter VT;Madrigal JA;Mayor NP;Marsh SGE
供体杀伤细胞免疫球蛋白样受体（KIR）基因对造血细胞移植（HCT）结果的影响是相互矛盾的，部分原因是不同研究中疾病、供体来源、时代和预处理方案的多样性。在这里，我们描述了一项回顾性临床分析的结果，该分析建立了供体KIR基序对119例HLA匹配的无关供体HCT的结果的影响，这些HCT用于在主要T细胞耗竭（TCD）队列中使用清髓性预处理（MAC）治疗成人急性髓性白血病（AML）。我们观察到涉及具有至少一种KIR B单倍型的供体的HCT比涉及具有两种KIR A单倍型的供体的HCT更可能导致非复发死亡率（NRM）（p=0.019）。在将KIR单倍型分离成它们的着丝粒（Cen）和端粒（Tel）基序结构后，我们证明Cen-B基序在很大程度上负责这种效应（p=0.001）。当进一步研究NRM的原因时，感染是死亡的主要原因（p=0.006）。没有观察到供体KIR B单倍型与复发风险相关的证据。该分析的结果证实了先前在无关、TCD、MAC移植设置中的发现，并暗示了供体编码的Cen-A基序对同种异体HCT接受者中的感染的保护作用。
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.
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影响因子：
20.3
作者：
Kollman, Craig;Spellman, Stephen R.;Eapen, Mary
通讯作者：
Eapen, Mary
影响因子：
20.3
作者：
Cooley, S;McCullar, V;Miller, JS
通讯作者：
Miller, JS
影响因子：
20.3
作者：
Cooley, Sarah;Trachtenberg, Elizabeth;Weisdorf, Daniel J.
通讯作者：
Weisdorf, Daniel J.
影响因子：
4.4
作者：
Fischer, Johannes C.;Ottinger, Hellmut;Uhrberg, Markus
通讯作者：
Uhrberg, Markus
DOI：
10.1016/s1470-2045(12)70004-9
发表时间：
2012-04
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Fleischhauer K;Shaw BE;Gooley T;Malkki M;Bardy P;Bignon JD;Dubois V;Horowitz MM;Madrigal JA;Morishima Y;Oudshoorn M;Ringden O;Spellman S;Velardi A;Zino E;Petersdorf EW;International Histocompatibility Working Group in Hematopoietic Cell Transplantation
通讯作者：
International Histocompatibility Working Group in Hematopoietic Cell Transplantation