期刊
LEUKEMIA & LYMPHOMA
卷 55, 期 4, 页码 786-794出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2013.818142
关键词
Zidovudine; Epstein-Barr virus; human immunodeficiency virus; non-Hodgkin lymphoma; plasmablastic lymphoma; primary central nervous system lymphoma
资金
- Leukemia and Lymphoma Society
- PHS grant [CA019014]
- NIH-Center for AIDS Research grant [5P30AI073961-05]
- University of Miami Sylvester Comprehensive Cancer Center
- NIH-NCI [5R01CA112217, 2U01CA121947, PO1-CA-128115-01A2]
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.
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