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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2005-12-1
pubmed:abstractText
Valproic acid (VPA) inhibits histone deacetylase activity and induces differentiation of acute myeloid leukemia (AML) blasts in vitro. We observed clinical responses to VPA in patients with myelodysplastic syndrome (MDS) and AML. Here, we report follow-up data on 75 patients. Of these, 66 were started on VPA monotherapy, with later addition of all-trans retinoic acid (ATRA) in patients who did not respond or relapsed. Nine patients were treated with VPA + ATRA from the start. Median treatment duration was 4 months for VPA and 2 months for ATRA. Hematological improvement, according to international working group criteria for MDS, was observed in 18 patients (24%). Median response duration was 4 months. ATRA exerted no additional effect in patients receiving the combination from the start or benefited primary VPA nonresponders. However, of ten VPA responders who relapsed, four achieved a second response after addition of ATRA. Response rates were strongly dependent on disease type according to WHO classification. We found a response rate of 52% in MDS patients with a normal blast count (refractory sideroblastic anemia, refractory cytopenia with multilineage dysplasia, and refractory sideroblastic cytopenia with multilineage dysplasia). The response rate was 6% in refractory anemia with excess blasts (I + II), 16% in AML, and 0% in chronic myelomonocytic leukemia. Bone marrow blast count was the only variable that predicted responses. We conclude that VPA is clinically useful in low-risk MDS. For patients with high-risk MDS, VPA may be combined with chemotherapy or demethylating drugs. If patients relapse after an initial response to VPA, ATRA has the potential to induce a prolonged second response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1432-0584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
84 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-6
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16270213-Acute Disease, pubmed-meshheading:16270213-Adult, pubmed-meshheading:16270213-Aged, pubmed-meshheading:16270213-Aged, 80 and over, pubmed-meshheading:16270213-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:16270213-Cell Differentiation, pubmed-meshheading:16270213-Female, pubmed-meshheading:16270213-Histone Deacetylase Inhibitors, pubmed-meshheading:16270213-Histone Deacetylases, pubmed-meshheading:16270213-Humans, pubmed-meshheading:16270213-Kaplan-Meier Estimate, pubmed-meshheading:16270213-Leukemia, Myeloid, pubmed-meshheading:16270213-Male, pubmed-meshheading:16270213-Middle Aged, pubmed-meshheading:16270213-Myelodysplastic Syndromes, pubmed-meshheading:16270213-Remission Induction, pubmed-meshheading:16270213-Treatment Outcome, pubmed-meshheading:16270213-Tretinoin, pubmed-meshheading:16270213-Valproic Acid
pubmed:year
2005
pubmed:articleTitle
Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia.
pubmed:affiliation
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany. kuendgen@med.uni-duesseldorf.de
pubmed:publicationType
Journal Article, Comparative Study, Clinical Trial, Phase II