Clinical impact of cell-free serum Epstein–Barr virus status in patients with newly diagnosed malignant lymphoma
Dong Won Baek1, Jung Min Lee1, Juhyung Kim1, Hee Jeong Cho1, Sang Kyun Sohn1, Ji Yeon Ham2, Soon Hee Chang2, Joon Ho Moon1, Deok-Hwan Yang3
1Department of Hematology/Oncology, 2Department of Laboratory Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, 3Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, School of Medicine, Chonnam National University, Hwasun, Korea
Correspondence to: Joon Ho Moon, M.D., Ph.D.
Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea
E-mail: jhmoon@knu.ac.kr
Deok-Hwan Yang, M.D., Ph.D.
Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, School of Medicine, Chonnam National University, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeonnam 58128, Korea
E-mail: drydh1685@hotmail.com
Published online: May 25, 2021.
© The Korean Journal of Hematology. All rights reserved.

Abstract
Background : We analyzed cell-free serum Epstein–Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma.
Patients and Methods: 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.
Results: 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).
Conclusion: 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.
Keywords: Epstein–Barr virus, Lymphoma, Prognosis, Biomarker


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