title: Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid.
abstract: Valproic acid (VPA) has been shown to inhibit histone deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in the differentiation induction of acute myelogenous leukemia (AML) blasts in vitro. We treated 18 patients with myelodysplastic syndromes (MDS) and AML secondary to MDS (sAML/MDS) with VPA monotherapy (serum concentrations 346-693 microM [50-100 microg/mL]). Five patients received VPA and ATRA (80 mg/m(2)/d, days 1-7, every other week). Response according to international working group (IWG) criteria was observed in 8 patients (44%) on VPA monotherapy, including 1 partial remission. Median response duration was 4 months (range, 3-9 months). Four of 5 patients relapsing were treated with VPA + ATRA, 2 of them responding again. Among 5 patients receiving VPA + ATRA from the start, none responded according to IWG criteria, but 1 patient with sAML/MDS achieved a marked reduction in peripheral and marrow blasts. Thus, VPA is of therapeutic benefit for patients with MDS, and ATRA may be effective when added later.
authors.affiliation: Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany. andrea@ta2000.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuendgen
authors.forename: Corinna
authors.initials: C
authors.lastname: Strupp
authors.forename: Manuel
authors.initials: M
authors.lastname: Aivado
authors.forename: Alf
authors.initials: A
authors.lastname: Bernhardt
authors.forename: Barbara
authors.initials: B
authors.lastname: Hildebrandt
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Norbert
authors.initials: N
authors.lastname: Gattermann
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage*; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D014212:Tretinoin; D014635:Valproic Acid