title: Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas.
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 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.
authors.affiliation: Division of Hematology/Oncology.
authors.forename: Ulas Darda
authors.initials: UD
authors.lastname: Bayraktar
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Brittany
authors.initials: B
authors.lastname: Ashlock
authors.forename: Ngoc
authors.initials: N
authors.lastname: Toomey
authors.forename: Lisa
authors.initials: L
authors.lastname: Cabral
authors.forename: Soley
authors.initials: S
authors.lastname: Bayraktar
authors.forename: Denise
authors.initials: D
authors.lastname: Pereira
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramos
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D012074:Remission Induction; D012189:Retrospective Studies; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D015215:Zidovudine; D008727:Methotrexate