Valproic Acid for the Treatment of Myeloid Malignancies

Abstract

We 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 μg/mL. Of evaluable patients (n = 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. Payal Shah BA*, Anthony Mato MD*, Selina M. Luger MD*, * Leukemia Program, Division of Hematology-Oncology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.