Einsele H, Ehninger G, Hebart H, Wittkowski K M, Schuler U, Jahn G, Mackes P, Herter M, Klingebiel T, Löffler J, Wagner S, Müller C A
Medizinische Klinik und Poliklinik, Abteilung II, Universität Tübingen, Germany.
Blood. 1995 Oct 1;86(7):2815-20.
Culture-based preemptive therapy with ganciclovir was shown to reduce the incidence of cytomegalovirus (CMV) disease after bone marrow transplantation (BMT). Culture techniques did not detect CMV in 12% to 13% of patients before the onset of CMV disease. In a prospective study, 71 patients either received preemptive therapy based on polymerase chain reaction (PCR) technique (37 patients) or on culture assays (34 patients). In both groups, therapy was continued until clinical signs disappeared and PCR negativity was documented. Twenty-two patients in the PCR group and 15 patients in the culture group received antiviral therapy. PCR allowed detection of the virus (median day, +32 v day +49; P = .006) and introduction of antiviral therapy (median day, +44 v day +54; P = .02) earlier than did culture assays. The incidences of CMV disease (2 of 37 v 8 of 34 in PCR group v culture group, respectively; P = .02) and CMV-associated mortality (0 of 37 v 5 of 34 in PCR group v culture group, respectively; P = .02) were decreased, and the duration of ganciclovir therapy (P < .001) was shorter in the PCR-monitored group. Incidence and median duration of severe neutropenia (less than 500/microL) were lower in the PCR group (two v eight episodes, P = .02; median duration, 1.5 v 5 days, P = .04), as was the incidence of nonviral infections during/after antiviral therapy (2 of 37 v 9 of 34; P = .012). Thus, preemptive therapy based on more sensitive detection methods such as the PCR assay reduces the incidence of CMV disease and CMV-related mortality. Additionally, stopping and withholding antiviral therapy in a PCR-negative patient is safe and allows reduction of the duration and side effects of antiviral therapy.
更昔洛韦基于培养的抢先治疗被证明可降低骨髓移植（BMT）后巨细胞病毒（CMV）疾病的发生率。在CMV疾病发作前，培养技术在12%至13%的患者中未检测到CMV。在一项前瞻性研究中，71例患者要么接受基于聚合酶链反应（PCR）技术的抢先治疗（37例患者），要么接受基于培养检测的治疗（34例患者）。在两组中，治疗持续至临床症状消失且记录到PCR阴性。PCR组的22例患者和培养组的15例患者接受了抗病毒治疗。与培养检测相比，PCR能更早地检测到病毒（中位天数，+32天对+49天；P = 0.006）并开始抗病毒治疗（中位天数，+44天对+54天；P = 0.02）。PCR组的CMV疾病发生率（分别为37例中的2例对培养组34例中的8例；P = 0.02）和CMV相关死亡率（分别为37例中的0例对培养组34例中的5例；P = 0.02）均降低，且在PCR监测组中更昔洛韦治疗的持续时间更短（P < 0.001）。PCR组严重中性粒细胞减少（低于500/μL）的发生率和中位持续时间更低（分别为2次对8次发作，P = 0.02；中位持续时间，1.5天对5天，P = 0.04），抗病毒治疗期间/之后非病毒感染的发生率也是如此（37例中的2例对34例中的9例；P = 0.012）。因此，基于更敏感检测方法（如PCR检测）的抢先治疗可降低CMV疾病的发生率和CMV相关死亡率。此外，在PCR阴性的患者中停止和停用抗病毒治疗是安全的，且可减少抗病毒治疗的持续时间和副作用。
