Clinical Significance of Plasma and Peripheral Blood Mononuclear Cell EBV-DNA in Lymphoma

Epstein Barr virus (EBV) is a ubiquitous virus that establishes latent infection in the host and plays a critical role in the development and prognosis of lymphomas. The presence of EBV-DNA in peripheral blood is a widely used tumor marker. However, there is no consensus on the preferred blood compartment for EBV-DNA testing.

We retrospectively analyzed data from 256 lymphoma patients, including 21 with Hodgkin lymphoma, 96 with B-cell lymphoma, and 139 with T-cell or NK/T-cell lymphoma. Complete matched PBMC and plasma EBV-DNA datasets were available, allowing correlation analysis and assessment of their respective clinical significance.

Detectable pretreatment EBV-DNA in either plasma or PBMCs was significantly associated with worse survival outcomes (p < 0.001), with the worst prognosis observed in patients positive in both compartments. Longitudinal monitoring demonstrated that patients with negative EBV-DNA or declining viral loads in PBMCs or plasma had significantly improved progression-free survival compared to those with persistent positivity or increasing copy numbers (p < 0.001). Notably, changes in plasma EBV-DNA levels showed higher accuracy than PBMC EBV-DNA in reflecting treatment response. Multivariate analysis identified PBMC EBV-DNA positivity as an independent prognostic factor for inferior OS (p = 0.031) and PFS (p = 0.003).

Both plasma and PBMC EBV-DNA are valuable for prognostic evaluation in lymphoma patients. Plasma EBV-DNA demonstrates superior utility for monitoring treatment response, whereas PBMC EBV-DNA provides stronger prognostic information. Selection of the appropriate sample type should be tailored to the clinical context.