Extranodal NK/T-cell lymphoma (ENKTCL) is a unique hematological malignancy characterized by predominantly extranodal involvement and invariably Epstein-Barr virus (EBV) positivity. EBV infection of lymphoma cells is the pathogenic basis of ENKTCL, and the presence of EBV-DNA in peripheral blood is a tumor marker widely used for response evaluation and relapse monitoring. EBV-DNA levels at diagnosis and at the end of treatment have been documented to correlate well with prognosis [1, 2]. Elevated EBV-DNA levels prior to and after treatment are associated with poorer survival [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. However, there is no consensus on which blood compartment is preferred for EBV-DNA testing. Both plasma [3], [4], [5], [6] and whole blood [7], [8], [9], [10], [11], [12] are used clinically as testing specimens. Most reported data tested viral load in only one of these two blood compartments. A recent study comparatively analyzed the prognostic value of plasma and whole blood EBV-DNA in 60 patients with ENKTCL. There were 37 pairs of matched whole blood and plasma EBV-DNA data at diagnosis and 23 pairs at the end of treatment. The results showed that plasma EBV-DNA positivity but not whole blood EBV-DNA positivity was independently associated with poor survival [13]. It is unknow why the discrepancy existed. In addition, discordance between EBV-based disease assessment and imaging-based assessment is common in practice. When faced with positive EBV-DNA and negative imaging or negative EBV-DNA and positive imaging, it is difficult for practitioners to interpret the results and thus make informed decisions.

We attempted to address the above-mentioned issues in this retrospective study. Whole blood EBV-DNA load consists of two sources: plasma EBV-DNA and peripheral blood mononuclear cell (PBMC) EBV-DNA. Our institution routinely tests PBMC and plasma EBV-DNA, not whole blood EBV-DNA, so we compared the clinical relevance of plasma and PBMC EBV-DNA.