Oxidative stress markers and tissue iron overload after 12-months vitamin E supplementation for children with transfusion-dependent β-thalassemia on different iron chelators: A randomized placebo-controlled trial.

Abstract

BACKGROUND: Vitamin E is an anti-oxidant depleted in thalassemia as a result of iron overload. AIM: We investigated the efficacy and safety of vitamin E as an adjuvant therapy to iron chelators in transfusion-dependent thalassemia patients in relation to tissue iron overload and examine its potential corrective value to oxidative stress markers including peroxiredoxin-2 (PRDX2). METHODS: This randomized prospective study included 180 pediatric patients with transfusion-dependent β-thalassemia who were equally divided into three groups to either receive desferrioxamine (DFO), deferiprone (DFP) or deferasirox (DFX). Patients in each group were further randomized to receive vitamin E supplementation (400 mg daily) or matching placebo. Patients were followed-up for 12 months with assessment of oxidative stress markers (malondialdehyde [MDA], reduced glutathione, superoxide dismutase, glutathione peroxidase and PRDX2), serum ferritin (SF), liver iron content (LIC) and cardiac T2∗ by magnetic resonance imaging. The primary endpoint was the change between groups from baseline to 12 months as regards LIC. RESULTS: After vitamin E therapy, transfusion index, SF and LIC were significantly decreased while hemoglobin and cardiac T2∗ were elevated compared with baseline levels or placebo group. MDA levels were decreased while the studied antioxidants were improved after vitamin E supplementation compared with baseline levels or placebo. DFX-treated patients had the highest hemoglobin level with the lowest SF, LIC and MDA levels compared with DFO or DFP subgroups. CONCLUSIONS: Vitamin E is a safe adjuvant anti-oxidant therapy that potentiates the efficacy of DFX in reducing iron burden in transfusion-dependent β-thalassemia patients. This trial was registered under ClinicalTrials.gov Identifier no. NCT06509581.