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骨髓移植患者巨细胞病毒载量的纵向波动:病毒载量峰值、供体/受体血清学状态、急性移植物抗宿主病与巨细胞病毒疾病之间的关系

Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease.

作者信息

Gor D, Sabin C, Prentice H G, Vyas N, Man S, Griffiths P D, Emery V C

机构信息

Department of Virology, Royal Free Hospital and School of Medicine, London, UK.

出版信息

Bone Marrow Transplant. 1998 Mar;21(6):597-605. doi: 10.1038/sj.bmt.1701139.

DOI:10.1038/sj.bmt.1701139
PMID:9543064
Abstract

Quantitative competitive PCR was used to monitor the quantity of cytomegalovirus (HCMV) in 1647 blood samples from 110 BMT recipients. DNAemia was detected in 49/110 (45%) of the patients, of whom 15/49 experienced HCMV disease. Peak virus load during surveillance was elevated in symptomatic (median 4.5 log10 genomes/ml) vs asymptomatic patients (median 3.6 log10 genomes/ml, P=0.002) and was also significantly elevated in HCMV seropositive recipients of seronegative marrow, (R+D-, median 5.0 log10), compared to those in the R-D- and R+D+ groups (P < 0.01 and <0.005). Odds ratios for disease per 0.25 log10 increase in viral load, recipient seropositivity and aGVHD were 1.43 (P=0.004), 6.60 (P=0.05) and 3.17 (P=0.08), respectively. In multivariate logistic regression analysis only elevated viral load remained a significant risk factor for HCMV disease. The computed disease probability viral load curve showed a rapid increase in disease risk at viral loads between 3.8 and 5.5 log10 genomes/ml in blood, and odds ratios for disease were determined for different threshold viral loads. These data demonstrate the central role of viral load in the pathogenesis of HCMV in BMT recipients and provide an additional marker for targeting and monitoring therapy.

摘要

采用定量竞争性聚合酶链反应(PCR)监测110例骨髓移植(BMT)受者的1647份血样中的巨细胞病毒(HCMV)数量。110例患者中有49例(45%)检测到病毒血症,其中15例发生HCMV疾病。有症状患者监测期间的病毒载量峰值(中位数为4.5 log10基因组/ml)高于无症状患者(中位数为3.6 log10基因组/ml,P=0.002),HCMV血清学阴性骨髓的HCMV血清学阳性受者(R+D-,中位数为5.0 log10)的病毒载量峰值也显著高于R-D-和R+D+组(P<0.01和<0.005)。病毒载量每增加0.25 log10、受者血清学阳性和急性移植物抗宿主病(aGVHD)的疾病比值比分别为1.43(P=0.004)、6.60(P=0.05)和3.17(P=0.08)。在多因素逻辑回归分析中,只有病毒载量升高仍然是HCMV疾病的显著危险因素。计算得出的疾病概率-病毒载量曲线显示,血液中病毒载量在3.8至5.5 log10基因组/ml之间时,疾病风险迅速增加,并针对不同的病毒载量阈值确定了疾病比值比。这些数据证明了病毒载量在BMT受者HCMV发病机制中的核心作用,并为靶向治疗和监测提供了一个额外的标志物。

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