Blood:半相合HSCT后应用环磷酰胺管理对NK细胞的影响。

2017-10-08 qinqiyun MedSci原创

移植后应用环磷酰胺(PT-Cy)来预防移植物抗宿主病(GvHD)为半相合HSCT带来革命性的变化,使移植未处理过的T淋巴细胞可安全进行。PT-Cy选择性地清除增殖的同种异体反应的T细胞,但PT-Cy怎样且如何影响NK细胞及其同种异体反应性基本尚不清楚。

中心点:

移植后应用环磷酰胺可清除移植中的大部分成熟的供体NK细胞,包括同种异体反应的NK细胞。

HSCT后早期,高水平的白介素-15可为成熟的供体NK细胞的过渡提供良好的环境。

摘要:

移植后应用环磷酰胺(PT-Cy)来预防移植物抗宿主病(GvHD)为半相合HSCT带来革命性的变化,使移植未处理过的T淋巴细胞可安全进行。PT-Cy选择性地清除增殖的同种异体反应的T细胞,但PT-Cy怎样且如何影响NK细胞及其同种异体反应性基本尚不清楚。

研究人员在两个独立的中心对17位接受未经处理的半相合移植(包括大量成熟NK细胞)的患者的NK细胞的动力学进行表征。

HSCT后密切记录供者衍生的NK细胞的增殖情况。注射环磷酰胺后,NK细胞的增殖出现明显下降,表明环磷酰胺可选择性的清除分裂细胞。

在体外,增殖的NK细胞不表达醛脱氢酶,并可被PT-Cy杀死,支持上述推论。

从HSCT后15天开始,成熟的NK细胞被清除后,在高水平的白介素-15的作用下,未成熟的NK细胞(CD62L+NKG2A+KIR-)明显增多,可能是直接来源于注射的HSCs。

此外还推测同种异体反应的单KIR+的NK细胞也可被PT-Cy清除,其数目和抗白血病的潜能在HSCT后30天出现降低。

在用PT-Cy管理的另外99例单-HSCT中,有无预测NK同种异体反应性的患者之间的无进展生存期无显着差异(42% vs 52%)。

数据表明在PT-Cy管理下,未经处理的移植物中的大部分成熟NK细胞会丧失,NK细胞的同种异体反应性也会钝化。

原始出处:

Antonio Russo,et al.NK cell recovery after haploidentical HSCT with post-transplant cyclophosphamide: dynamics and clinical implications.Blood.October 06,2017.https://doi.org/10.1182/blood-2017-05-780668

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    2018-07-07 智智灵药
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    2017-10-09 Y—xianghai

    学习了新知识

    0

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    2017-10-09 飛歌

    不错学习了很有用

    0

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已有研究表明,口服12个月的环磷酰胺 vs 安慰剂,可改变硬皮病相关间质性肺疾病的进展。但是毒性情况如何?且不继续治疗的话,疗效是否会小时?我们假设,相比环磷酰胺,霉酚酸酯治疗2年是安全的,且具有更好的耐受性,并能产生更为持久的改善。 这项随机、双盲、平行对照试验,纳入了来自14个美国医疗中心的硬皮病相关肺间质病变患者,符合呼吸困难、肺功能及高分辨率CT(HRCT)诊断标准。将患者随机分配到