title: Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report.
abstract: Histone deacetylase inhibitors are a class of anti-neoplastic agents that induce growth arrest, differentiation, and/or apoptotic cell death of transformed cells in vitro and in vivo. A phase II study exploring the efficacy of romidepsin, an histone deacetylase inhibitor, in patients with cutaneous or peripheral T-cell lymphomas was initiated at the National Cancer Institute. To date, over 120 patients with T-cell lymphoma have been treated on a multi-institutional phase II trial of romidepsin. Reactivation of latent DNA viruses including EBV, HBV, and VZV is well described as a consequence of the immune suppression associated with systemic chemotherapy. The incidence of viral reactivation in patients treated with histone deacetylase inhibitors is not yet known. We report the observation of EBV-associated illnesses in 2 patients and the reactivation of HBV in an additional patient treated with romidepsin. These cases may represent reactivation of DNA viruses due to histone deacetylase inhibitor induced immunosuppression, or direct promotion of viral replication via histone deacetylase inhibitor induced chromatin remodeling, or, alternatively, may be related to the underlying disease process. These observations suggest that vigilance for DNA virus reactivation is needed to quantify the risk in patients treated with histone deacetylase inhibitors.
authors.affiliation: Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria 3002, Australia. david.ritchie@petermac.org
authors.forename: David
authors.initials: D
authors.lastname: Ritchie
authors.forename: Richard L
authors.initials: RL
authors.lastname: Piekarz
authors.forename: Piers
authors.initials: P
authors.lastname: Blombery
authors.forename: Laszlo J
authors.initials: LJ
authors.lastname: Karai
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004267:DNA Viruses / Q000502:physiology*; D047630:Depsipeptides / Q000009:adverse effects*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000150:complications / Q000188:drug therapy; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; C087123:romidepsin