Zidovudine-based lytic-inducing chemotherapy for Epstein - Barr virus-related lymphomas

Treatment of Epstein – Barr virus (EBV)-related lymphomas with lytic-inducing agents is an attractive targeted approach for eliminating virus-infected tumor cells. Zidovudine (AZT) is an excellent substrate for EBV-thymidine kinase: it can induce EBV lytic gene expression and apoptosis in primary EBV lymphoma cell lines. We hypothesized that the combination of AZT with lytic-inducing chemotherapy agents would be eff ective in treating EBV lymphomas. We report a retrospective analysis of 19 patients with aggressive EBV non-Hodgkin lymphoma, including nine cases of acquired immune defi ciency syndromeassociated primary central nervous system lymphoma (AIDSPCNSL) treated with AZT-based chemotherapy. Our results demonstrate that high-dose AZT – methotrexate is effi cacious in treating highly aggressive systemic EBV lymphomas in the upfront setting. In primary EBV lymphoma cell lines, the combination of AZT with hydroxyurea resulted in synergistic EBV lytic induction and cell death. Further, AZT – hydroxyurea treatment resulted in dramatic responses in patients with AIDSPCNSL. The combination of AZT with chemotherapy, especially lytic-inducing agents, should be explored further in clinical trials for the treatment of EBV-related lymphomas.