Gärtner Barbara C, Schäfer Hansjörg, Marggraff Katja, Eisele Günter, Schäfer Marco, Dilloo Dagmar, Roemer Klaus, Laws Hans-Jürgen, Sester Martina, Sester Urban, Einsele Hermann, Mueller-Lantzsch Nikolaus
Department of Virology, University of Homburg/Saar, Homburg/Saar, Germany.
J Clin Microbiol. 2002 Feb;40(2):351-8. doi: 10.1128/JCM.40.2.351-358.2002.
Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disease (PTLD) continues to be a serious complication following transplantation. The aim of the present study was to evaluate the EBV load as a parameter for the prediction and monitoring of PTLD. The EBV load was analyzed by a quantitative competitive PCR with 417 whole-blood samples of 59 patients after allogeneic stem cell transplantation (SCT). The EBV load was positive for all 9 patients with PTLD and for 17 patients without PTLD. The viral loads of patients with manifest PTLD differed from the loads of those without PTLD (median loads, 1.4 x 10(6) versus 4 x 10(4) copies/microg of DNA; P < 0.0001). A threshold value of 10(5) copies/microg of DNA showed the best diagnostic efficacy (sensitivity, 87%; specificity, 91%). However, in patients with less than three major risk factors for PTLD, the positive predictive value of this threshold was rather low. One week prior to the manifestation of PTLD, the EBV load was as low in patients who developed PTLD as in patients without disease (median, 2.2 x 10(4) copies/microg of DNA; P was not significant). EBV DNA tested positive first at 20 to 71 days prior to the clinical manifestation of PTLD and occurred with the same delay after transplantation regardless of disease (median delay, 52 versus 63 days; P was not significant). EBV DNA was detected earlier in patients with primary infections than in those with reactivations (33 versus 79 days; P = 0.01), but the peak levels were similar in the two groups. EBV primary infection or EBV reactivation is frequent in patients after allogeneic SCT but results in PTLD only in a subgroup of patients. Although evaluation of the EBV load has limitations, the EBV load represents a valuable parameter to guide therapy.
爱泼斯坦-巴尔病毒（EBV）所致的移植后淋巴细胞增生性疾病（PTLD）仍是移植后的一种严重并发症。本研究的目的是评估EBV载量作为预测和监测PTLD的一个参数。采用定量竞争PCR分析了59例异基因干细胞移植（SCT）后患者的417份全血样本的EBV载量。9例PTLD患者和17例无PTLD患者的EBV载量均为阳性。有明显PTLD的患者的病毒载量与无PTLD的患者不同（中位载量，1.4×10⁶对4×10⁴拷贝/μg DNA；P<0.0001）。DNA拷贝数/μg为10⁵的阈值显示出最佳诊断效能（敏感性，87%；特异性，91%）。然而，在PTLD主要危险因素少于三个的患者中，该阈值的阳性预测值相当低。在PTLD出现前一周，发生PTLD的患者的EBV载量与未患病患者一样低（中位值，2.2×10⁴拷贝/μg DNA；P无显著性）。EBV DNA在PTLD临床表现前20至71天首次检测为阳性，且移植后出现延迟的时间相同，与疾病无关（中位延迟，52天对63天；P无显著性）。原发性感染患者比再激活患者更早检测到EBV DNA（33天对79天；P = 0.01），但两组的峰值水平相似。异基因SCT后患者中EBV原发性感染或EBV再激活很常见，但仅在部分患者亚组中导致PTLD。尽管评估EBV载量有局限性，但EBV载量是指导治疗的一个有价值的参数。
