title: Sodium valproate in combination with ganciclovir induces lysis of EBV-infected lymphoma cells without impairing EBV-specific T-cell immunity.
abstract: Histone deacytelase inhibitiors (HDACi) represent a new class of anti-lymphoma therapeutics. Data in the clinical setting regarding on- and off-target effects of these agents are limited. Epstein-Barr virus (EBV)-positive lymphomas represent a highly defined system in which to make these observations. We present a case of a patient with multiple relapsed EBV-positive Diffuse Large B-cell Lymphoma that was chemo-refractory to anthracylcines, alkylating agents and rituximab. Treatment was commenced with the HDACi sodium valproate (VPA) in combination with the anti-viral nucleoside analogue ganciclovir (GCV). Therapy resulted in detectable cell-free unencapsulated circulating EBV-DNA providing supportive evidence for the first-time that lysis of virus infected lymphoma cells is induced using this therapeutic combination. EBV-specific CD8+ effector T-cell immunity was not impaired by VPA/GCV. Although GCV/VPA was insufficient to induce clinical remission, our data furthers the rationale that more potent HDAC inhibitors such as butyrate or gemcitabine together with GCV, perhaps in combination with chemotherapy, should be further investigated as therapy in relapsed/refractory EBV-positive lymphomas.
authors.affiliation: Clinical Immunohaematology Lab, Queensland Institute of Medical Research, Brisbane, Qld, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Nourse
authors.forename: G
authors.initials: G
authors.lastname: Corbett
authors.forename: M K
authors.initials: MK
authors.lastname: Gandhi
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D017809:Fatal Outcome; D015774:Ganciclovir / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D013601:T-Lymphocytes / Q000821:virology; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D015774:Ganciclovir