Lack of Efficacy of Pyridoxine (Vitamin B6) Treatment In Acquired Idiopathic Sideroblastic Anemia, Including Refractory Anemia with Ring Sideroblasts

Abstract 2919 Background: Sideroblastic anemias can be either hereditary due to congenital mutations in factors critical for iron processing or heme biosynthesis, or acquired; acquired sideroblastic anemias may be induced by alcohol or medications, but are usually idiopathic. Pyridoxine, a form of vitamin B6, plays a critical role in heme synthesis as a cofactor for δ-aminolevulinic acid synthetase (ALAS). Some subtypes of congenital sideroblastic anemia, such as those associated with mutations in the ALAS2 gene encoding the erythrocyte-expressed isoform of ALAS, may respond to pyridoxine therapy at doses ranging from 5–500 mg/day. Anecdotal reports of improvement with pyridoxine therapy in cases of acquired idiopathic sideroblastic anemia (AISA) have led to widespread clinical use of this agent in patients with refractory anemia with ring(ed) sideroblasts (RARS) and refractory cytopenia with multilineage dysplasia associated with ring sideroblasts (RCMD-RS). However, there are no systematic studies of the effectiveness of pyridoxine in AISA. Methods: We reviewed clinical and laboratory data from 231 adult patients with marrow aspirate-proven AISA (i.e., RARS or RCMD-RS, based on 2001 WHO criteria) evaluated at our institution between 1994 and 2007. Responses to pyridoxine were assessed using 2006 International Working Group (IWG) standardized criteria for MDS (erythroid response with hemoglobin increase by 91.5 mg/dl). The relationship between response to pyridoxine and disease subtype or International Prognostic Scoring System (IPSS) stratification was assessed using χ2 test, using a p-value limit of Results: 86 of the 231 patients (42%) were treated with pyridoxine for an average of 19 months (range 1–114 months) at a mean dose of 167 mg/day (range 50–600 mg/day). Sufficient follow-up data to allow response evaluation were available from 74 (86%) of the 86 patients who received pyridoxine. Only 5/86 patients (6.8%) receiving pyridoxine met IWG response criteria for hematological improvement, but 3 of these 5 patients also received erythropoetin and 1 also received prednisone concomitantly with pyridoxine therapy. Therefore, only 1/86 (1.4%) patient9s improvement in hemoglobin could be attributed to pyridoxine monotherapy. ALAS2 genotype data were not available from these 5 patients. The dose of pyridoxine was not associated with response to therapy (187.5 mg daily in responders vs. 157 mg daily in non-responders (p=0.60). Patients with RCMD-RS were more likely to be treated with vitamin B6 compared to patients with RARS (p= Conclusions: Pyridoxine is commonly prescribed to patients with AISA in clinical practice, and this agent is often continued for a long period of time despite lack of evidence of objective response. Pyridoxine is an ineffective therapy in AISA that induces symptomatic peripheral neuropathy in some patients. Therefore, pyridoxine therapy should be limited to patients with known or suspected congenital mutations that confer pyridoxine responsiveness, and therapeutic trials should be brief to avoid adverse effects. Disclosures: No relevant conflicts of interest to declare.