Severe Hematologic Toxicity of Valproic Acid

Ganick, Dorothy J.; Sunder, Theodore R.; Finley, James M.

doi:10.1097/00043426-199021000-00016

Cited by 62 publications

(29 citation statements)

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“…Hematologic toxicity has been reported to rarely occur during anticonvulsive therapy with VPA. 28,29 The hematologic For personal use only. on May 11, 2018.…”

Section: Discussionmentioning

confidence: 99%

Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients

Tassara

Döhner

Brossart

et al. 2014

Blood

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Key Points• The addition of valproic acid to intensive induction therapy in combination with all-trans retinoic acid did not result in an improvement of clinical outcome.• Valproic acid-related hematologic toxicity and higher death rates were observed when valproic acid and idarubicin were given in parallel.The outcome of patients with acute myeloid leukemia who are older than 60 years has remained poor because of unfavorable disease characteristics and patient-related factors.The randomized German-Austrian AML Study Group 06-04 protocol was designed on the basis of in vitro synergistic effects of valproic acid (VPA) and all-trans retinoic acid with chemotherapy. Between 2004 and 2006, 186 patients were randomly assigned to receive 2 induction cycles with idarubicin, cytarabine, and all-trans retinoic acid either with VPA or without (STANDARD). In all patients, consolidation therapy was intended. Complete remission rates after induction tended to be lower in VPA compared with STANDARD (40% vs 52%; P 5 .14) as a result of a higher early death rate (26% vs 14%; P 5 .06). The main toxicities attributed to VPA were delayed hematologic recovery and grade 3/4 infections, observed predominantly during the second induction cycle. After restricting VPA to the first induction cycle and reducing the dose of idarubicin, these toxicities dropped to rates observed in STANDARD. After a median follow-up time of 84 months, event-free and overall survival were not different between the 2 groups (P 5 .95 and P 5 .57, respectively). However, relapse-free-survival was significantly superior in VPA compared with STANDARD (24.4% vs 6.4% at 5 years; P 5 .02). Explorative subset analyses revealed that AML with mutated Nucleophosmin 1 (NPM1) may particularly benefit from VPA. This trial was registered at www.clinicaltrials.gov as #NCT00151255. (Blood. 2014;123(26):4027-4036)

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“…Hematologic toxicity has been reported to rarely occur during anticonvulsive therapy with VPA. 28,29 The hematologic For personal use only. on May 11, 2018.…”

Section: Discussionmentioning

confidence: 99%

Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients

Tassara

Döhner

Brossart

et al. 2014

Blood

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“…Serious, but reversible, hematologic toxicity resembling a myelodysplastic syndrome (MDS) has also been reported. Four patients were reported to have thrombocytopenia, macrocytosis, the Pelger-Huet abnormality, and trilineage dysplasia in the bone marrow associated with valproic acid [7]. Hongeng et al reported a case of anemia, thrombocytopenia, and myelodysplastic changes in the marrow, which resolved with a decrease in valproic acid dose [8].…”

Section: Introductionmentioning

confidence: 99%

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

et al. 2005

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Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase. Am.

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“…In previous study, the reported frequency of VPA-induced thrombocytopenia has varied greatly and ranged from 0% to 32%. 7,10,[12][13][14][15][16][17][18][19] The strength of our study is that we conducted a longitudinal observational study in which the sequential assessment of platelets counts was done monthly to analyze the effect of VPA on platelet count.…”

Section: Discussionmentioning

confidence: 99%

Occurrences of thrombocytopenia with valproic acid used for psychiatric indication

Sahu

Hishikar

Sahu

et al. 2015

Int J Basic Clin Pharmacol

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Severe Hematologic Toxicity of Valproic Acid

Cited by 62 publications

References 0 publications

Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients

Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

Occurrences of thrombocytopenia with valproic acid used for psychiatric indication

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