Hubácek P, Cinek O, Kulich M, Zajac M, Keslová P, Formánková R, Starý J, Sedlácek P
Klinika dĕtské hematologie a onkologie 2, LF UK a FNM, Praha.
Cas Lek Cesk. 2006;145(4):301-6.
Patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) are endangered by developing Epstein-Barr virus-related post-transplant lymfoprolipherative disease (EBV-LPD). The aims of the study were to retrospectively characterise the viral loads in four patients who died of this complication, and to test possible risk factors for EBV reactivation in a prospectively observed cohort of children after AHSCT.
Serial DNA samples extracted from whole blood from four patients who died of post-transplant EBV-LPD in year 2000 were retrospectively analysed for EBV load using quantitative real-time PCR. First detection of EBV activation preceded death by 24-91 days. All four patients exceeded a viral load of one million EBV copies per 100,000 human genome equivalents. A cohort of 72 children undergoing AHSCT between 2001-2004 was prospectively followed-on using the same quantification method from regularly obtained samples of whole blood, and clinical and laboratory data were recorded on a weekly basis, totalling at 3,896 person-weeks of observation. Approximately one half of the cohort experienced at least one episode of EBV reactivation during the first 100 days after AHSCT, four of the episodes being accompanied with viral loads higher than our provisional threshold of 10,000 copies per 100,000 human genome equivalents. Three of the four patients developed EBV-LPD and were successfully treated by intravenous administration of anti-CD20 antibody. Testing of possible clinical and laboratory predictors of EBV reactivation did not reveal any clinically useful association.
The cornerstone of predicting EBV-LPD in AHSCT is a regular monitoring of EBV viral load using quantitative methods. Using this strategy with a threshold of 10,000 EBV copies per 100,000 human genome equivalents was proved to be effective, as shown by no death of EBV for the study period, compared to four cases in the year before the quantitative monitoring.
接受异基因造血干细胞移植（AHSCT）的患者面临发生与 Epstein-Barr 病毒相关的移植后淋巴细胞增殖性疾病（EBV-LPD）的风险。本研究的目的是回顾性分析 4 例死于该并发症患者的病毒载量，并在前瞻性观察的 AHSCT 后儿童队列中检测 EBV 重新激活的可能危险因素。
对 2000 年死于移植后 EBV-LPD 的 4 例患者的全血提取的系列 DNA 样本进行回顾性分析，使用定量实时 PCR 检测 EBV 载量。首次检测到 EBV 激活发生在死亡前 24 - 91 天。所有 4 例患者的病毒载量均超过每 100,000 人类基因组当量 100 万份 EBV 拷贝。对 2001 年至 2004 年间接受 AHSCT 的 72 例儿童队列进行前瞻性随访，使用相同的定量方法对定期采集的全血样本进行检测，并每周记录临床和实验室数据，总计观察 3896 人周。大约一半的队列在 AHSCT 后的前 100 天内至少经历了一次 EBV 重新激活，其中 4 次发作的病毒载量高于我们临时设定的每 100,000 人类基因组当量 10,000 拷贝的阈值。4 例患者中有 3 例发生了 EBV-LPD，并通过静脉注射抗 CD20 抗体成功治疗。对 EBV 重新激活的可能临床和实验室预测指标的检测未发现任何具有临床意义的关联。
预测 AHSCT 中 EBV-LPD 的关键是使用定量方法定期监测 EBV 病毒载量。与定量监测前一年的 4 例病例相比，本研究期间未发生 EBV 相关死亡，证明使用每 100,000 人类基因组当量 10,000 份 EBV 拷贝的阈值的这一策略是有效的。
