Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation
Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation
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DOI：
10.1182/blood-2009-08-236943
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发表时间：
2010-04-15
期刊：
影响因子：
20.3
通讯作者：
Hsu, Katharine C.
中科院分区：
文献类型：
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作者：
Venstrom, Jeffrey M.;Gooley, Ted A.;Hsu, Katharine C.
自然杀伤细胞受体 KIR3DS1 与恶性肿瘤、感染和自身免疫性疾病的预后改善相关，但 KIR3DS1 对 HSCT 影响的数据并不一致。使用国家骨髓捐赠计划的基因组 DNA，我们对 1087 名接受无关造血干细胞移植的患者进行了捐赠者 KIR 基因分型。共有 33% 的捐赠者为 KIR3DS1(+)。与 KIR3DS1(-) 供者相比，供者 KIR3DS1 与较低级别的 II-IV 期急性移植物抗宿主病相关（GVHD；比值比 = 0.71；95% 置信区间，0.55-0.92；P=.009），但与复发无关（风险比 = 0.97；95% 置信区间，0.73-1.29；P=.009）。 P=.82)。此外，随着供体 KIR3DS1 拷贝数的增加，II-IV 级急性 GVHD、总死亡率和移植相关死亡率均下降（分别为 P=.007、P=.03 和 P=.02），其中供体 KIR3DS1 纯合子患者的失败率最低。选择带有 KIR3DS1 的供体可以减少急性 GVHD，而不影响无复发生存，从而将移植物抗肿瘤效应与不需要的 GVHD 分开。 （血。2010；115(15):3162-3165）
The natural killer cell receptor KIR3DS1 is associated with improved outcome in malignancies, infections, and autoimmune diseases, but data for the impact of KIR3DS1 in HSCT are inconsistent. Using genomic DNA from the National Marrow Donor Program, we performed donor KIR genotyping for 1087 patients who received an unrelated hematopoietic stem cell transplantation. A total of 33% of donors were KIR3DS1(+). Compared with KIR3DS1(-) donors, donor KIR3DS1 was associated with lower-grade II-IV acute graft-versus-host disease (GVHD; odds ratio = 0.71; 95% confidence interval, 0.55-0.92; P=.009), but not with relapse (hazard ratio = 0.97; 95% confidence interval, 0.73-1.29; P=.82). Furthermore, grade II-IV acute GVHD, overall mortality, and transplantation-related mortality all decreased as the number of copies of donor KIR3DS1 increased (P=.007, P=.03, and P=.02, respectively), with the lowest failure rate occurring among patients homozygous for donor KIR3DS1. Selection of donors with KIR3DS1 may decrease acute GVHD without compromising relapse-free survival, separating the graft-versus-tumor effect from unwanted GVHD. (Blood. 2010;115(15):3162-3165)