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

Ulas Darda Bayraktar, Luis A. Diaz, Brittany Ashlock, Ngoc Toomey, Lisa Cabral, Soley Bayraktar, Denise Pereira, Dirk P. Dittmer, Juan Carlos Ramos

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 syndromeassociated primary central nervous system lymphoma (AIDSPCNSL) 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 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.

Original languageEnglish (US)
Pages (from-to)786-794
Number of pages9
JournalLeukemia and Lymphoma
Volume55
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Epstein-Barr virus
  • Human immunodeficiency virus
  • Non-Hodgkin lymphoma
  • Plasmablastic lymphoma
  • Primary central nervous system lymphoma
  • Zidovudine

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Bayraktar, U. D., Diaz, L. A., Ashlock, B., Toomey, N., Cabral, L., Bayraktar, S., Pereira, D., Dittmer, D. P., & Ramos, J. C. (2014). Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. Leukemia and Lymphoma, 55(4), 786-794. https://doi.org/10.3109/10428194.2013.818142