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

• Published in: Clinical cancer research 2011-05, Vol.17 (9), p.2885-2892
• Main Authors: HOHAUS, Stefan, SANTANGELO, Rosaria, VOSO, Maria Teresa, FADDA, Giovanni, LEONE, Giuseppe, LAROCCA, Luigi M, GIACHELIA, Manuela, VANNATA, Barbara, MASSINI, Giuseppina, CUCCARO, Annarosa, MARTINI, Maurizio, CESARINI, Valeriana, CENCI, Tonia, D'ALO, Francesco
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biopsy; Cancer; Cell number; copy number; Data processing; DNA, Viral - analysis; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - virology; Female; Geriatrics; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - growth & development; Hodgkin Disease - complications; Hodgkin Disease - diagnosis; Hodgkin Disease - drug therapy; Hodgkin Disease - virology; Hodgkin's disease; Humans; Immunosurveillance; Infectious diseases; Interleukin 6; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (mononuclear); Lymph nodes; Macrophages; Male; Medical sciences; Middle Aged; Peripheral blood; Pharmacology. Drug treatments; Polymerase chain reaction; Prognosis; Serology; Viral diseases; Viral Load - physiology; Young Adult
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-10-3327

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. 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 = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n = 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels. 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 CD68+ 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. 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.