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 L Pereira, Dirk P. Dittmer, Juan Carlos Ramos

Research output: Contribution to journalArticle

11 Citations (Scopus)

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
Pages (from-to)786-794
Number of pages9
JournalLeukemia and Lymphoma
Volume55
Issue number4
DOIs
StatePublished - Jan 1 2014

Fingerprint

Zidovudine
Human Herpesvirus 4
Lymphoma
Drug Therapy
Hydroxyurea
Central Nervous System
Virus Activation
Cell Line
Oncogenic Viruses
Thymidine Kinase
Methotrexate
Non-Hodgkin's Lymphoma
Cell Death
Therapeutics
Clinical Trials
Apoptosis
Gene Expression

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

Cite this

Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. / Bayraktar, Ulas Darda; Diaz, Luis A.; Ashlock, Brittany; Toomey, Ngoc; Cabral, Lisa; Bayraktar, Soley; Pereira, Denise L; Dittmer, Dirk P.; Carlos Ramos, Juan.

In: Leukemia and Lymphoma, Vol. 55, No. 4, 01.01.2014, p. 786-794.

Research output: Contribution to journalArticle

Bayraktar, UD, Diaz, LA, Ashlock, B, Toomey, N, Cabral, L, Bayraktar, S, Pereira, DL, Dittmer, DP & Carlos Ramos, J 2014, 'Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas', Leukemia and Lymphoma, vol. 55, no. 4, pp. 786-794. https://doi.org/10.3109/10428194.2013.818142
Bayraktar UD, Diaz LA, Ashlock B, Toomey N, Cabral L, Bayraktar S et al. Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. Leukemia and Lymphoma. 2014 Jan 1;55(4):786-794. https://doi.org/10.3109/10428194.2013.818142
Bayraktar, Ulas Darda ; Diaz, Luis A. ; Ashlock, Brittany ; Toomey, Ngoc ; Cabral, Lisa ; Bayraktar, Soley ; Pereira, Denise L ; Dittmer, Dirk P. ; Carlos Ramos, Juan. / Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. In: Leukemia and Lymphoma. 2014 ; Vol. 55, No. 4. pp. 786-794.
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