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A pilot trial of quantitative Epstein–Barr virus polymerase chain reaction in patients undergoing treatment for their malignancy: potential use of Epstein–Barr virus polymerase chain reaction in multiple cancer types

Epstein – Barr virus (EBV) is a herpes virus that infects over 90% of the world ’ s population. After primary infection, the virus enters an asymptomatic latent phase that typically lasts the remainder of life. However, under certain circumstances – such as extreme age or in the setting of immunosuppression – the virus may reactivate and express genes that contribute to neoplastic transformation. A variety of malignancies have been associated with EBV reactivation, including Hodgkin lymphoma, several non-Hodgkin lymphoma subtypes (Burkitt lymphoma, post-transplant lymphoproliferative disorder [PTLD] and EBV-associated diff use large B-cell lymphoma [DLBCL] of the elderly) and nasopharyngeal carcinoma [1 – 5]. In patients with EBV-driven malignancy, EBV can be detected within malignant cells as well as in the patient ’ s blood. Quantitative EBV viral load measurement by polymerase chain reaction (EBV PCR) has been used as a marker for disease activity in selected EBV-associated malignancies. In acquired immune defi ciency syndrome (AIDS)-related lymphomas and PTLD, the presence and degree of EBV viremia has been established as a marker of disease activity, facilitating both diagnosis and response assessment [6,7]. In Hodgkin lymphoma, the presence of EBV viremia has been shown to be prognostic at baseline and post-treatment [8]. EBV PCR has shown promise in these diseases as a tool for conveniently and non-invasively monitoring the activity of an EBV-associated tumor. While EBV PCR has been found to be clinically useful in the management of some EBV-associated lymphomas, there are malignancies for which the association with EBV is uncertain, and for which the use of EBV viral load assessment for diagnosis and response monitoring is unknown. To explore the use of EBV PCR for the diagnosis and monitoring of malignancy, we conducted an institutional review board approved prospective clinical trial of quantitative whole blood (WB) and plasma (P) EBV PCR