Zidovudine-based lytic-inducing chemotherapy for Epstein–Barr virus-related lymphomas. Issue 4 (April 2014)

• Record Type: Journal Article
• Authors: Bayraktar, Ulas Darda; Diaz, Luis A.; Ashlock, Brittany; Toomey, Ngoc; Cabral, Lisa; Bayraktar, Soley; Pereira, Denise; Dittmer, Dirk P.; Ramos, Juan Carlos
• Is Part Of: Leukemia & lymphoma. Volume 55:Issue 4(2014:Apr.)
• Page Start: 786
• Page End: 794
• Publication Date: 2014-04
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.818142
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>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 effective in treating EBV+ lymphomas. We report a retrospective analysis of 19 patients with aggressive EBV+ non-Hodgkin lymphoma, including nine cases of acquired immune deficiency syndrome-associated primary central nervous system lymphoma (AIDS-PCNSL) treated with AZT-based chemotherapy. Our results demonstrate that high-dose AZT–methotrexate is efficacious 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 AIDS-PCNSL. The combination of AZT with chemotherapy, especially lytic-inducing agents, should be explored further in clinical trials for the treatment of EBV-related lymphomas.</p> </abstract>