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同种异体干细胞移植背景下初次及复发性巨细胞病毒(CMV)感染急性期患者的 CMV 血浆 DNA 血症动力学:对设计抢先性抗病毒治疗策略的影响。

Dynamics of cytomegalovirus (CMV) plasma DNAemia in initial and recurrent episodes of active CMV infection in the allogeneic stem cell transplantation setting: implications for designing preemptive antiviral therapy strategies.

机构信息

Microbiology Service Hospital Clínico Universitario, Valencia, Spain.

出版信息

Biol Blood Marrow Transplant. 2011 Nov;17(11):1602-11. doi: 10.1016/j.bbmt.2011.08.014. Epub 2011 Aug 24.

Abstract

Preemptive antiviral therapy strategies for active cytomegalovirus (CMV) infection occurring in allogeneic stem cell transplant recipients should be optimized to avoid overtreatment. The current study was aimed at determining whether the analysis of the kinetics of CMV DNA load in plasma may provide useful information for the therapeutic management of active CMV infection in this setting. A total of 59 consecutive patients were included in the study, of which 40 (67.8%) developed 1 (n = 21) or more (n = 19) episodes of CMV DNAemia. The need for antiviral therapy for initial or secondary episodes of CMV DNAemia could not be predicted on the basis of the CMV DNA load value in the first plasma testing positive by polymerase chain reaction (PCR). In contrast, in the absence of antiviral therapy, an increase of ≥3-fold between the baseline CMV DNA load and that measured a median of 6 days later discriminated between initial episodes eventually requiring antiviral treatment and those resolving spontaneously (sensitivity, 76.4%; specificity, 89.4%; positive predictive value, 86.6%; negative predictive value, 80.9%). This criterion was not useful for identifying recurrent episodes of CMV DNAemia that required antiviral therapy. The CMV doubling time and CMV DNA loads at the time of the first positive PCR and at initiation of preemptive therapy did not differ significantly between episodes that responded immediately to antiviral therapy from those showing a delayed response. The analysis of the dynamics of CMV DNA load in plasma in the absence of antiviral therapy allowed early recognition of episodes of CMV DNAemia that eventually needed to be treated, but did not permit prediction of the kinetics of CMV DNA clearance in response to antiviral therapy.

摘要

对于异基因干细胞移植受者中发生的活动性巨细胞病毒 (CMV) 感染,应优化预防性抗病毒治疗策略以避免过度治疗。本研究旨在确定分析血浆中 CMV DNA 负荷的动力学是否可为该环境中活动性 CMV 感染的治疗管理提供有用信息。共纳入 59 例连续患者,其中 40 例(67.8%)发生 1 次(n=21)或更多次(n=19)CMV DNA 血症。基于聚合酶链反应 (PCR) 首次检测到阳性的血浆中 CMV DNA 负荷值,无法预测初始或继发 CMV DNA 血症的抗病毒治疗需求。相比之下,在未进行抗病毒治疗的情况下,基线 CMV DNA 负荷与中位时间为 6 天后测量的 CMV DNA 负荷之间的增加≥3 倍,可区分最终需要抗病毒治疗的初始发作与自发消退的发作(敏感性,76.4%;特异性,89.4%;阳性预测值,86.6%;阴性预测值,80.9%)。该标准对于识别需要抗病毒治疗的复发性 CMV DNA 血症发作并不有用。首次 PCR 阳性时和开始预防性治疗时的 CMV 倍增时间和 CMV DNA 载量在立即对抗病毒治疗有反应的发作与表现出延迟反应的发作之间没有显著差异。在没有抗病毒治疗的情况下分析 CMV DNA 负荷的动力学,可以早期识别最终需要治疗的 CMV DNA 血症发作,但不能预测抗病毒治疗后 CMV DNA 清除的动力学。

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