Gandhi Maher K, Lambley Eleanore, Burrows Jacqueline, Dua Ujjwal, Elliott Suzanne, Shaw Peter J, Prince H Miles, Wolf Max, Clarke Kerrie, Underhill Craig, Mills Tony, Mollee Peter, Gill Devinder, Marlton Paula, Seymour John F, Khanna Rajiv
Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia.
Clin Cancer Res. 2006 Jan 15;12(2):460-4. doi: 10.1158/1078-0432.CCR-05-2008.
Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and quantitation of EBV viral DNA could potentially be used as a biomarker of disease activity.
Initially, EBV-DNA viral load was prospectively monitored from peripheral blood mononuclear cells (PBMC) in patients with HL. Subsequently, we analyzed viral load in plasma from a second cohort of patients. A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long-term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples were analyzed.
EBV-DNA was detectable in the plasma of all EBV-positive patients with HL prior to therapy. However, viral DNA was undetectable following therapy in responding patients (P = 0.0156), EBV-positive HL patients in long-term remission (P = 0.0011), and in all patients with EBV-negative HL (P = 0.0238). Conversely, there was no association seen for the EBV-DNA load measured from PBMC in patients with active EBV-positive HL patients as compared with EBV-negative HL, or patients in long-term remission. EBV-DNA load in matched plasma/PBMC samples were not correlated.
We show that free plasma EBV-DNA has excellent sensitivity and specificity, and can be used as a noninvasive biomarker for EBV-positive HL and that serial monitoring could predict response to therapy. Additional prospective studies are required to further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring response to treatment in patients with EBV-positive HL.
在大约三分之一的霍奇金淋巴瘤（HL）病例的恶性细胞中发现了潜伏性爱泼斯坦-巴尔病毒（EBV）基因组。EBV病毒DNA的检测和定量可能用作疾病活动的生物标志物。
最初，对HL患者外周血单个核细胞（PBMC）中的EBV-DNA病毒载量进行前瞻性监测。随后，我们分析了第二批患者血浆中的病毒载量。共检测了58例HL患者（31例新诊断患者、6例复发患者和21例长期缓解患者）。使用实时PCR分析了43份PBMC和52份血浆样本。
所有EBV阳性的HL患者在治疗前血浆中均可检测到EBV-DNA。然而，在有反应的患者（P = 0.0156）、长期缓解的EBV阳性HL患者（P = 0.0011）以及所有EBV阴性HL患者（P = 0.0238）中，治疗后病毒DNA检测不到。相反，与EBV阴性HL患者或长期缓解患者相比，在活跃的EBV阳性HL患者中，从PBMC测得的EBV-DNA载量没有相关性。匹配的血浆/PBMC样本中的EBV-DNA载量不相关。
我们表明游离血浆EBV-DNA具有出色的敏感性和特异性，可作为EBV阳性HL的非侵入性生物标志物，并且连续监测可预测治疗反应。需要进一步的前瞻性研究来进一步评估游离血浆EBV-DNA作为监测EBV阳性HL患者治疗反应生物标志物的用途。
