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同种异体造血干细胞移植后患者中扭转型病毒的动态变化和免疫标志物特征:一项前瞻性纵向研究。

Torquetenovirus Dynamics and Immune Marker Properties in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Longitudinal Study.

机构信息

Division of Blood and Marrow Transplantation, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Division of Blood and Marrow Transplantation, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

出版信息

Biol Blood Marrow Transplant. 2018 Jan;24(1):194-199. doi: 10.1016/j.bbmt.2017.09.020. Epub 2017 Oct 12.

Abstract

Torquetenovirus (TTV) has been proposed as a marker of immune function in patients receiving immunosuppression after solid organ transplantation. This study aimed to define TTV plasma dynamics and investigate clinical associations in patients following allogeneic hematopoietic stem cell transplantation (HSCT). This was a single-center prospective longitudinal study involving 50 consecutive patients treated with HSCT between March 2015 and April 2016. TTV plasma DNA levels were measured with quantitative PCR at 12 consecutive time points during the first year after HSCT. Forty of the 50 patients (80%) had detectable TTV viremia before HSCT (median level, 5.37 log10 copies/mL; interquartile range [IQR], 3.51-6.44 log10 copies/mL). All patients subsequently developed TTV viremia during the follow-up period. Plasma viral loads evolved dynamically over time, with a peak of 8.32 log10 copies/mL (IQR, 7.33-9.35 log10 copies/mL) occurring at 79 days (IQR, 50-117 days) following HSCT and a stable plateau toward the end of the follow-up period. The type of malignancy, the use of antithymocyte globulin during conditioning, and the occurrence of acute graft-versus-host disease requiring systemic therapy had temporary effects on TTV dynamics. TTV levels showed a significant correlation with absolute lymphocyte counts following engraftment (r = -.27; P < .01) and with cytomegalovirus (CMV; r=.39; P < .01) and Epstein-Barr virus (EBV; r=.45; P = .02) viral loads during phases of viremia. Immune-related clinical events were not predicted by TTV levels. TTV viremia occurred universally and was sustained throughout the first year after HSCT. Several variables and events before and after HSCT were correlated with TTV levels and hint toward immune marker properties of TTV, but their complex interactions might perturb the capability of TTV to predict immune-related complications in this population.

摘要

Torquetenovirus (TTV) 已被提议作为实体器官移植后接受免疫抑制治疗的患者免疫功能的标志物。本研究旨在定义 TTV 血浆动力学,并在异基因造血干细胞移植 (HSCT) 后患者中调查临床相关性。这是一项涉及 2015 年 3 月至 2016 年 4 月期间接受 HSCT 的 50 例连续患者的单中心前瞻性纵向研究。在 HSCT 后第一年的 12 个连续时间点用定量 PCR 测量 TTV 血浆 DNA 水平。在 HSCT 前,50 例患者中的 40 例(80%)可检测到 TTV 病毒血症(中位数水平为 5.37 log10 拷贝/mL;四分位距 [IQR],3.51-6.44 log10 拷贝/mL)。所有患者随后在随访期间均发生 TTV 病毒血症。血浆病毒载量随时间动态变化,在 HSCT 后 79 天(IQR,50-117 天)出现 8.32 log10 拷贝/mL(IQR,7.33-9.35 log10 拷贝/mL)的峰值,并在随访末期趋于稳定。恶性肿瘤的类型、在调理期间使用抗胸腺细胞球蛋白以及需要系统治疗的急性移植物抗宿主病的发生对 TTV 动力学具有暂时影响。TTV 水平与植入后的绝对淋巴细胞计数呈显著相关性(r = -.27;P < .01),与病毒血症期间的巨细胞病毒(CMV;r=.39;P < .01)和 EBV(r=.45;P = .02)病毒载量呈显著相关性。免疫相关临床事件不受 TTV 水平预测。HSCT 后普遍发生 TTV 病毒血症,并持续整个第一年。HSCT 前后的几个变量和事件与 TTV 水平相关,并暗示 TTV 具有免疫标志物特性,但它们的复杂相互作用可能会干扰 TTV 预测该人群中免疫相关并发症的能力。

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