Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin's lymphomas

Purpose: This study aimed at correlating Epstein-Barr virus (EBV) infection of systemic AIDS-related non-Hodgkin lymphomas (AIDS-NHL) with the develop ment of a CNS localization of the tumor, Patients and Methods: Demographic, epidemiologic, clinical, histologic, and virologic features were collected for all systemic AIDS-NHL patients inclu ded in the study(n = 50), pathologic specimens were classified according to the working formulation for NHL and the Revised European-American Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV s mall encoded RNA in situ hybridization; EBV-DNA detection in CSF was carrie d out by nested polymerase chain reaction using Epstein-Barr nuclear antige n-1-specific primers. In addition, selected EBV-positive lymphomas were sub jected to a detailed characterization of EBV molecular heterogeneity. Results: Eleven patients had a CNS involvement at some point during their c linical history (four at diagnosis and seven at relapse). Thirty patients ( 11 with CNS involvement and 19 without) harbored EBV infection of the tumor . Sensitivity, specificity, and positive and negative predictive values of EBV-DNA detection in CSF for CNS involvement by lymphoma were 90%, 100%, 10 0%, and 97.6%, respectively. Factors significantly predictive of CNS involv ement were EBV infection of the tumor (P =.003), an extranodal disease at d iagnosis other than CNS (P =.006), and a non-CNS relapse (P =.01), In four cases of CNS involvement, EBV-DNA in CSF preceded any other sign of disease by a mean of 35 days. Conclusion: These results show that EBV infection of the tumor clone signif icantly increases the risk of CNS involvement by systemic AIDS-NHL, without regard of specific molecular features. The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with higher risk of CNS involvement and, therefore, may prove useful in the therapeutic stratification of these tumors. J Clin Oncol 18:3325-3330. (C) 2000 by American Society of Clinica l Oncology.