Blood Res.  2021 Jun;56(2):65-71. 10.5045/br.2021.2021028.

Clinical impact of cell-free serum Epstein–Barr virus status in patients with newly diagnosed malignant lymphoma

  • 1Departments of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
  • 2Departments of Laboratory Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
  • 3Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, School of Medicine, Chonnam National University, Hwasun, Korea


We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma.
We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study.
Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033).
We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.


Epstein‒Barr virus; Lymphoma; Prognosis; Biomarker


  • Fig. 1 Kaplan–Meier curves for long-term survival outcomes. Patients with positive serum EBV status showed inferior (A) PFS and (B) OS compared with EBV-negative patients.

  • Fig. 2 Kaplan–Meier curves for long-term survival outcomes. In the B-cell lymphoma group, serum EBV-positive patients showed inferior (A) PFS and (B) OS compared with EBV-negative patients.

  • Fig. 3 Kaplan–Meier curves for long-term survival outcomes. In the T-cell lymphoma group, serum EBV positivity was not a significant factor affecting (A) PFS. However, EBV-positive patients showed inferior (B) OS.


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