Quantification of EBV DNA In Whole Blood In Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma

Epstein-Barr virus (EBV) is a well-known oncogenic virus associated with the development of several lymphoproliferative disorders. The quantification of EBV viral load in plasma and peripheral blood mononuclear cells has been reported as a useful biomarker for EBV-associated non-Hodgkin lymphoma (NHL). The role of EBV in diffuse large B-cell lymphoma (DLBCL) is unclear at this time. METHODS: In the present prospective study, using real-time quantitative polymerase chain reaction (RQ-PCR), whole blood specimens from patients with a new diagnosis of DLBCL were used to quantitatively determine EBV viral load. Consecutive patients who presented from January 1, 2009 to December 30, 2009 were selected for this study. The pathological samples from the patients showing elevated EBV DNA levels were then investigated for the presence of EBV-encoded RNA (EBER) using a chromogenic in situ hybridization (CISH) technique. Clinical data from these patients was collected and analyzed, and will be presented using descriptive statistics. Overall survival estimates were obtained using the Kaplan-Meier method.

Forty six patients with a new diagnosis of DLBCL were included in our study; from which five cases showed elevated levels of EBV DNA by RQ-PCR (10.8%). These five patients (100%) were positive for EBER expression within the tumoral cells by EBER CISH. One patient was evaluated at the end of treatment and blood EBV DNA level was undetectable. All EBV DNA-positive cases were male with a median age of 69 years (range 25–73 years); only one case was younger than 50 years. The median EBV DNA viral load was 59 copies/uL (range 0.225–43200 copies/uL). Three patients (60%) presented with advanced clinical stage (III or IV) and three patients (60%) had a primary extranodal site of involvement. Four patients (80%) received CHOP-based chemotherapy regimens. The three patients with advanced stage have deceased with a survival of <3 months. The two patients with early stage experienced a complete response with immunochemotherapy and are alive 6 and 9 months after diagnosis, respectively. The median overall survival is 4 months.

These results, although preliminary, suggest that whole blood EBV DNA quantification might be useful at detecting patients with EBV-positive DLBCL. Further studies are needed to investigate the potential diagnostic and/or prognostic value of EBV DNA in DLBCL.

No relevant conflicts of interest to declare.