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异基因造血干细胞移植受者全血和血浆中巨细胞病毒和 EBV 病毒 DNA 动力学。

Cytomegalovirus and Epstein-Barr Virus DNA Kinetics in Whole Blood and Plasma of Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

机构信息

Microbiology Unit, Laboratory of Virology, Department of Specialized, Experimental, Diagnostic Medicine, St. Orsola-Malpighi Polyclinic, University of Bologna, Bologna, Italy.

Molecular Virology Unit, Microbiology and Virology Department, Foundation IRCCS Polyclinic San Matteo, Pavia, Italy.

出版信息

Biol Blood Marrow Transplant. 2018 Aug;24(8):1699-1706. doi: 10.1016/j.bbmt.2018.03.005. Epub 2018 Mar 12.

Abstract

Currently, no consensus has been reached on the optimal blood compartment to be used for surveillance of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia. Although several comparative studies have been performed correlating CMV and EBV DNA loads in whole blood (WB) versus plasma, to our knowledge, no studies to date have analyzed the kinetics of both viruses in the 2 blood compartments. In this retrospective noninterventional multicenter cohort study, the kinetics of CMV and EBV DNA in 121 hematopoietic stem cell transplantation (HSCT) recipients were investigated by analyzing in parallel 569 and 351 paired samples from 80 and 58 sequential episodes of CMV and EBV DNAemia, respectively. Unlike previous studies, this study used a single automated molecular method that was CE-marked and Food and Drug Administration-approved for use in quantifying CMV and EBV DNA in both plasma and WB. Furthermore, the complete viral replication kinetics of all episodes (including both the ascending and the descending phases of the active infection) was examined in each patient. The previously observed overall correlation between CMV DNA levels in WB and plasma was confirmed (Spearman's ρ = .85; P < .001). However, although WB and plasma CMV DNAemia reached peak levels simultaneously, in the ascending phase, the median CMV DNA levels in plasma were approximately 1 log10 lower than WB. Furthermore, in patients who received preemptive therapy, CMV DNA showed a delayed decrease in plasma compared with WB. A lower correlation between EBV DNA levels in plasma versus WB was found (Spearman's ρ = .61; P < .001). EBV DNA kinetics was not consistent in the 2 blood compartments, mostly due to the lower positivity in plasma. Indeed, in 19% of episodes, EBV DNA was negative at the time of the EBV DNA peak in WB. Our results suggest a preferential use of WB for surveillance of CMV and EBV infection in HSCT recipients.

摘要

目前,对于监测巨细胞病毒 (CMV) 和 Epstein-Barr 病毒 (EBV) 病毒血症,尚未达成最佳血液检测部位的共识。尽管已经进行了几项比较研究,将全血 (WB) 与血浆中的 CMV 和 EBV DNA 载量进行了相关分析,但据我们所知,迄今为止尚无研究分析过这两种病毒在这两种血液中的动力学。在这项回顾性、非干预性多中心队列研究中,通过同时分析 80 例连续 CMV 病毒血症和 58 例 EBV 病毒血症患者各 569 例和 351 对配对样本,研究了 121 例造血干细胞移植 (HSCT) 受者的 CMV 和 EBV DNA 动力学。与之前的研究不同,本研究使用了一种经 CE 标记和美国食品药品监督管理局批准的用于定量检测血浆和 WB 中 CMV 和 EBV DNA 的单一自动化分子方法。此外,在每个患者中都检查了所有感染期(包括感染活跃期的上升和下降阶段)的完整病毒复制动力学。之前观察到的 WB 和血浆中 CMV DNA 水平之间的总体相关性得到了证实(Spearman's ρ=.85;P<.001)。然而,尽管 WB 和血浆中的 CMV 病毒血症同时达到峰值,但在上升阶段,血浆中的 CMV DNA 水平中位数比 WB 低约 1 log10。此外,在接受抢先治疗的患者中,与 WB 相比,血浆中的 CMV DNA 下降延迟。在血浆中 EBV DNA 与 WB 之间发现的相关性较低(Spearman's ρ=.61;P<.001)。在这两种血液检测部位中,EBV DNA 的动力学并不一致,主要是由于血浆中的阳性率较低。实际上,在 19%的感染期,在 WB 中的 EBV DNA 峰值时,血浆中的 EBV DNA 呈阴性。我们的结果表明,在 HSCT 受者中,WB 更适合监测 CMV 和 EBV 感染。

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