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.

Détails

ID Serval
serval:BIB_87D4BAE36763
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Annals of hematology
Auteur(s)
Kuendgen A., Knipp S., Fox F., Strupp C., Hildebrandt B., Steidl C., Germing U., Haas R., Gattermann N.
ISSN
1432-0584 (Electronic)
ISSN-L
0939-5555
Statut éditorial
Publié
Date de publication
12/2005
Peer-reviewed
Oui
Volume
84 Suppl 1
Pages
61-66
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Comparative Study ; Journal Article
Publication Status: ppublish
Résumé
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.
Mots-clé
Acute Disease, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Cell Differentiation/drug effects, Female, Histone Deacetylase Inhibitors, Histone Deacetylases/drug effects, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid/drug therapy, Male, Middle Aged, Myelodysplastic Syndromes/drug therapy, Remission Induction, Treatment Outcome, Tretinoin/administration & dosage, Valproic Acid/therapeutic use
Pubmed
Web of science
Création de la notice
16/07/2019 12:30
Dernière modification de la notice
21/08/2019 5:37
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