Valproic Acid for the Treatment of Myeloid Malignancies W e read with interest Drs. Kuendgen and Gattermann's recent review on valproic acid (VPA) for the treatment of myeloid malignancies. 1 We suggest that response to VPA in myelodysplastic syndrome (MDS) patients may be underestimated in current literature because of relatively short durations of treatment in published studies. 2 At our institution, we conducted a pilot study of VPA monotherapy in MDS. 3 Patient response was assessed after 4-6 weeks of VPA at serum concentrations of 50-100 mg/mL. Of evaluable patients (n ΒΌ 15), 4 (27%) showed hematologic improvement (HI) per International Working Group criteria, 4 with responses seen only in patients with low-risk disease, consistent with results of Kuendgen et al. 1,2 One such subject, a 38-year-old female with no significant past medical history, presented with a 50-lb weight loss and symptomatic anemia. A diagnostic bone marrow revealed myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD). Her International Prognostic Scoring System (IPSS) score was 0 (3% blasts on aspirate; normal female karyotype; Hg, 9.3). She required red cell (PRBC) transfusions every 3 weeks. During Months 1-7 of VPA therapy, her median Hg rose to 9.8; she received 1 PRBC transfusion. Between Months 7-12 of therapy, her hemoglobin improved by an additional 3.1 g/dL. She reported increased energy and appetite and demonstrated a 23-lb weight gain. Her response at 4-6 weeks was characterized as HI-erythroid. 4 Her best response to VPA, a complete peripheral blood remission, occurred, however, after 7.5 months of continuous therapy and is sustained, now 32 months after initiation of therapy, with a median Hg of 13.2 during the last 2 years.
Our experience with VPA suggests that sustained responses to VPA monotherapy are possible; furthermore, similar to other epigenetic agents used in MDS, responses to VPA may not be apparent for months. 5 Patients with stable disease and minor responses may need treatment for longer durations before a final assessment is made. This observation may be important in designing future VPA and other HDAC-I studies for low-risk MDS patients.