title: Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia--a report of five cases.
abstract: Disease-stabilizing therapy with the histone deacetylase inhibitor valproic acid and all-trans retinoic acid (ATRA) has been investigated in acute myelogenous leukemia (AML) in a number of trials. Experimental studies suggest that valproic acid induces a broad chemoresistant phenotype in human AML cells; however, clinical observations combining valproic acid with conventional therapy in a disease-stabilizing setting have not been reported that would confirm this as a clinical issue. We describe five patients receiving oral treatment with low-dose oral 6-mercaptopurin and/or hydroxyurea together with ATRA+valproric acid+theophylline. Hyperleukocytosis was controlled by low doses of the cytotoxic drugs, no unexpected toxicity appeared and the increases in normal peripheral blood cell counts induced by ATRA+valproic acid+theophylline were maintained during therapy. In two patients increasing blast counts later occurred during chemotherapy; a change to the alternative cytotoxic drug was then effective in controlling hyperleukocytosis. We conclude that valproic acid+ATRA+theophylline combined with 6-mercaptopurin or hydroxyurea can be safe and effective in palliative treatment of human AML.
authors.affiliation: Section for Hematology, Institute of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Fredly
authors.forename: Camilla
authors.initials: C
authors.lastname: Stapnes Bjørnsen
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008875:Middle Aged; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D015122:Mercaptopurine; D006918:Hydroxyurea