The Turkish Journal of Pediatrics 2020 , Vol 62 , Num 4
Circulating Epstein-Barr virus DNA and cell-free DNA in pediatric lymphomas
Bilgehan Yalçın 1 ,Tezer Kutluk 1-2 ,Serpil Kahraman Ağbaba 2 ,Çetin Demir 2 ,Beril Talim 3
1 Department of Pediatric Oncology, Hacettepe University Cancer Institute and Faculty of Medicine, Ankara, Turkey
2 Drug Resistance Laboratory, Hacettepe University Oncology Hospital, Ankara, Turkey
3 Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
DOI : 10.24953/turkjped.2020.04.003 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 β-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. Keywords : Hodgkin lymphoma, non-Hodgkin lymphoma, serum Epstein-Barr virus, serum cell-free DNA, children

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