Circulating Epstein-Barr virus DNA and cell-free DNA in pediatric lymphomas

Background and objectives. Quantification of serum Epstein-Barr virus (EBV) DNA and/or cell-free total DNA (cf-DNA) may become valuable sources for prognosis evaluation and monitoring treatment response in lymphomas. We aimed to investigate their roles as potential markers in pediatric Hodgkin (HL) and non-Hodgkin lymphomas (NHL). Method. Between the years 2005-2008, 34 patients with HL and 45 with NHL were prospectively included. Serum samples were collected upon diagnosis, after 1-3 and 4-6 months and at the end of treatment, or at disease recurrence. RT-PCR determination of cf-DNA and EBV DNA were performed using amplification of BAMH1W region of EBV genome and of human beta-globin gene. Results were analyzed for correlation with clinical and pathological characteristics. Results. Median ages were 8.9 years for HL and 8.8 years for NHL cases. Twenty-three healthy children cured from various childhood cancers served as the control group. In the controls, median serum EBV DNA copy number was '0' and median serum cf-DNA level was 50 ng/ml. At initial diagnosis, serum EBV DNA copy numbers were elevated in 20/34 HL and 8/45 NHL cases (p<0.001). Median serum EBV DNA copy numbers were 15987/mL (125-6032075) and 25162 (1475-1214550) for HL and NHL cases, respectively (p= 0.9). Median serum cf-DNA levels were 435 ng/ml (2.3-17306) in HL and 700 ng/ml (4.9-14009) in NHLs (p= 0.12). Serum EBV DNA copy numbers and cf-DNA levels decreased significantly after induction treatment and in the follow-up. In 10/13 NHL cases with a relapse, marked elevations were detected in serum cf-DNA levels at recurrences. No significant differences were detected between median cf-DNA levels according to disease stages, response status to treatment or presence of recurrent disease. Conclusion. Serum EBV DNA copy numbers and cf-DNA levels were elevated at initial diagnosis in both HLs and NHLs and decreased parallel to treatment response. In NHL cases, remarkable elevation of cf-DNA levels at recurrences indicated that cf-DNA levels might be useful in the follow-up of pediatric NHLs.