Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid.
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.
Kuendgen
Andrea
A
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany. andrea@ta2000.de
Strupp
Corinna
C
Aivado
Manuel
M
Bernhardt
Alf
A
Hildebrandt
Barbara
B
Haas
Rainer
R
Germing
Ulrich
U
Gattermann
Norbert
N
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*
D000927:Anticonvulsants; D000970:Antineoplastic Agents; D014212:Tretinoin; D014635:Valproic Acid