Department of Clinical Medicine, Faculty of Medical Sciences, University of Campinas, P.O. Box 6111, Zipe Code 13083-970, Campinas, SP, Brazil.
BMC Infect Dis. 2010 Jun 1;10:147. doi: 10.1186/1471-2334-10-147.
Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications.
During the first 150 days after allogeneic HSTC, thirty patients were monitored weekly for active CMV infection by pp65 antigenemia, nested-PCR and real-time PCR assays. Receiver operating characteristic (ROC) plot analysis was performed to determine a threshold value of the CMV DNA load by real-time PCR.
Using ROC curves, the optimal cutoff value by real-time PCR was 418.4 copies/104 PBL (sensitivity, 71.4%; specificity, 89.7%). Twenty seven (90%) of the 30 analyzed patients had active CMV infection and two (6.7%) developed CMV disease. Eleven (40.7%) of these 27 patients had acute GVHD, 18 (66.7%) had opportunistic infection, 5 (18.5%) had chronic rejection and 11 (40.7%) died - one died of CMV disease associated with GVHD and bacterial infection.
The low incidence of CMV disease in HSCT recipients in our study attests to the efficacy of CMV surveillance based on clinical routine assay. The quantification of CMV DNA load using real-time PCR appears to be applicable to the clinical practice and an optimal cutoff value for guiding timely preemptive therapy should be clinically validated in future studies.
异基因造血干细胞移植(HSCT)后,人类巨细胞病毒(CMV)感染仍可导致显著的发病率和死亡率。因此,对 HSCT 患者进行主动 CMV 感染的诊断和监测极其重要,确定需要抗病毒药物干预的病毒复制的 CMV DNA 水平,以便准确预防 CMV 疾病和进一步相关并发症。
在异基因 HSTC 后的前 150 天内,通过 pp65 抗原血症、巢式 PCR 和实时 PCR 检测每周监测 30 例患者的活动性 CMV 感染。采用受试者工作特征(ROC)曲线分析确定实时 PCR 中 CMV DNA 载量的阈值值。
使用 ROC 曲线,实时 PCR 的最佳截断值为 418.4 拷贝/104 PBL(灵敏度为 71.4%,特异性为 89.7%)。分析的 30 例患者中有 27 例(90%)患有活动性 CMV 感染,其中 2 例(6.7%)发生 CMV 疾病。这 27 例患者中有 11 例(40.7%)患有急性移植物抗宿主病,18 例(66.7%)患有机会性感染,5 例(18.5%)患有慢性排斥反应,11 例(40.7%)死亡 - 1 例死于与 GVHD 和细菌感染相关的 CMV 疾病。
本研究中 HSCT 受者 CMV 疾病的发生率较低,证明了基于临床常规检测的 CMV 监测的有效性。使用实时 PCR 定量 CMV DNA 载量似乎适用于临床实践,未来研究中应在临床上验证指导及时抢先治疗的最佳截断值。