Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-11-04

AUTHORS

Andrea Kuendgen, Sabine Knipp, Frank Fox, Corinna Strupp, Barbara Hildebrandt, Christian Steidl, Ulrich Germing, Rainer Haas, Norbert Gattermann

ABSTRACT

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. More... »

PAGES

61-66

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00277-005-0026-8

DOI

http://dx.doi.org/10.1007/s00277-005-0026-8

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16270213


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68 effect
69 excess blasts
70 follow
71 hematological improvement
72 high-risk myelodysplastic syndrome
73 histone deacetylase activity
74 improvement
75 inhibits histone deacetylase activity
76 initial response
77 latest addition
78 leukemia
79 lower-risk myelodysplastic syndromes
80 marrow blast count
81 median response duration
82 median treatment duration
83 monotherapy
84 months
85 myelodysplastic syndrome
86 myeloid leukemia
87 myelomonocytic leukemia
88 nonresponders
89 only variable
90 patients
91 phase 2 study
92 potential
93 rate
94 refractory acute myeloid leukemia
95 refractory anemia
96 responders
97 response
98 response duration
99 response rate
100 results
101 retinoic acid
102 second response
103 start
104 study
105 syndrome
106 trans retinoic acid
107 treatment duration
108 types
109 valproic acid
110 variables
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