A Prospective Clinical Trial of a Novel Epstein-Barr Virus (EBV) PCR Panel in Patients with EBV Associated Malignancies.

EBV is known to be detectable within a number of different tumors, though the exact relationship between the malignant cells and the EBV virus is unknown in most cases. In post-transplant lymphoproliferative disorders, which are clearly EBV-driven, EBV PCR of peripheral blood has proven to be a clinically useful tumor marker. The goal of our study is to determine the utility of novel EBV PCR panel in EBV associated malignancies. Subjects with suspected active or untreated EBV-associated malignancies were evaluated with a 6 assay EBV PCR panel targeting LMP-1, EBER-1 and EBNA-1 within both whole blood cells and plasma. EBV positive subjects and EBV negative control tumor samples are tested for LMP and EBER using traditional histochemical staining. LDH, SPEP, and traditional EBV serology are also measured. Of the 40 patients who were evaluated to date, 18 subjects showed evidence of elevated blood EBV viral load: 3/5 nasopharyngeal carcinoma, 3/4 angioimmunoblastic lymphomas, 3/6 Hodgkin’s lymphomas, 4/10 peripheral T-cell lymphomas, 3/3 allogeneic bone marrow transplant lymphoproliferative disorders, 1/4 diffuse large B-cell lymphomas, 1/1 non-langerhans histiocytosis, and 0/7 low-grade B-cell NHL. Median DNA PCR copies/ml and ranges in EBV positive patients: EBNA plasma 500 (0–134,000), EBNA whole blood 700 (0–6,200), EBER plasma 200 (0–19,700), EBER whole blood 200 (0–1,000), LMP plasma 0 (0–600), LMP whole blood 0 (0–100). Patients were monitored with EBV PCR as they proceeded through treatment and 12 subjects are evaluable for response. Changes in viral load appear to be highly correlated with clinical tumor response (p=0.0013). 7/7 patients achieving CR had concurrent resolution of their plasma and whole blood EBV viral load. 5/5 patients with persistent disease had persistent elevated plasma and whole blood viral load. EBV histologic studies on the tumor samples are pending. Our data suggests that EBV PCR may be useful in the management of patients with EBV positive malignancies. Further patient enrollment and evaluation is ongoing.