The Viral Load of Epstein–Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma

Abstract

Purpose: The Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL.Experimental Design: EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n ¼ 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n ¼ 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels.Results: Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68þ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers.Conclusion: Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL. Clin Cancer Res; 17(9); 2885-92. Ó2011 AACR.

Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy

“…21 Circulating cell-free EBV-DNA levels can be detected using real-time quantitative RT-PCR in the blood of patients with EBV-associated tumors, such as nasopharyngeal carcinoma and Hodgkin lymphoma. [27][28][29] Previous studies have demonstrated that the EBV-DNA load correlates with clinical stage and can be used to monitor disease progression and predict prognosis. [27][28][29][30] Because of the rarity of the disease, the correlation between EBV-DNA levels and prognosis has been explored in small cohorts (n Ͻ 40) of NKTCL patients with different pathologic subtypes, clinical stages, primary locations, and treatment regimens.…”

“…[27][28][29] Previous studies have demonstrated that the EBV-DNA load correlates with clinical stage and can be used to monitor disease progression and predict prognosis. [27][28][29][30] Because of the rarity of the disease, the correlation between EBV-DNA levels and prognosis has been explored in small cohorts (n Ͻ 40) of NKTCL patients with different pathologic subtypes, clinical stages, primary locations, and treatment regimens. [31][32][33][34][35] The predictive value of potential biomarkers is dependent on the primary treatment, especially with the use of primary radiotherapy for earlystage NKTCL.…”

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

“…[19][20][21] Subsequent studies have been conducted to characterize the potential clinical applications of circulating EBV DNA in plasma for early detection and prognostic assessment of NPC. [22][23][24][25][26] It was reported that the circulating EBV DNA load can be used as an independent prognostic factor to UICC staging in NPC, while combining EBV DNA data with UICC staging data leads to alteration of the risk definitions for patient subsets. 24 However, no standardized EBV DNA test is currently available for clinical diagnosis of NPC.…”

Clinical Significance of Quantitative Analysis of Plasma Epstein-Barr Virus DNA in Patients of Xinjiang Uygur Nationality with Hodgkin's Lymphoma

“…EBV-DNA level of Uygur patients with HL was closely related to disease process. Hohaus et al (2011) researched 18 cases of HL and found that if patients with EBV-related HL had B symptom, median load of dissociated EBV-DNA in plasma could reach14380 copies/ml. While the copy median of EBV-DNA of patients without this symptom was 0 (P=0.001).…”