Cardiac damage caused by iron overload is the main cause of death in thalassemia. An increased risk of iron-induced cardiac disease is observed with liver iron concentration (LIC) values above 15mg of iron per gram of dry weight of liver, and in patients with serum ferritin values above 2500 microgram/liter. The rate of iron loading depends mainly on the rate of blood transfusions, which causes a net iron deposition in the body, of about 15-20 mg/day. In practice, the goal of chelation therapy is to achieve an iron balance by accessing two iron pools, namely intracellular labile iron pool (LIP) and iron from red cell catabolism [2].

After the introduction of deferoxamine in 1963, several efforts were made to synthesize orally active iron chelators. Following the screening of more than 700 chelators from various chemical classes, deferasirox emerged as a highly selective chelator for iron with high oral potency and tolerability. Deferasirox mobilizes iron stores by binding selectively to the ferric form of iron and enters most of the cells to reach the major intracellular sites of iron accumulation. For myocardial iron, deferasirox has the ability to enter myocardial cells and chelate iron from these cells. It was also observed from myocyte cultures that it rapidly gains entry in the myocytes and binds to labile intracellular iron, leading to decreased free radical production.

In recent years, clinical trials have been conducted to evaluate the effect of deferasirox on myocardial iron and the left ventricular ejection fraction (LVEF). Of the 23 patients who received deferasirox 10-30 mg/kg/day, for 13.1 (±0.78) months; the mean myocardial T2* measurement was inversely related to myocardial iron content. Deferasirox treatment led to significant reductions in mean serum ferritin concentrations and LICs, while no changes in LVEF were noted [3]. Study conducted by Pathare, et al. [4] monitored cardiac siderosis using T2 MRI in 19 heavily iron overloaded patients with β–thalassemia major receiving iron chelation therapy with deferasirox over an 18 months period. Deferasirox therapy significantly improved means cardiac T2 from a baseline of 17.2 (10.8) to 21.5 (12.8) ms. A concomitant reduction in median serum ferritin, and mean LIC was also noted. Improvements were seen in patients with various degrees of cardiac siderosis, including myocardial iron in those patients with a baseline cardiac T2 of <10ms, indicative of high cardiac iron burden [4].

Studies on long term use, dose, efficacy and safety profile of deferasirox have concluded that deferasirox in doses of 20-30 mg/kg/day could effectively reduce iron burden [5]. Further, efficacy of available chelators on myocardial iron and biventricular function by quantitative MRI in 550 thalassemics concluded that oral deferasirox has better global systolic ventricular function compared to oral deferiprone and subcutaneous desferoxamine [6].

In the background of such global studies, this prospective, open label, single arm study on 30 patients by Merchant, et al. [7] reported good safety profile of deferasirox, and showed that it effectively chelates myocardial iron, more efficacious in moderate to severe cardiac iron overload. In addition, there was a significant decrease in serum ferritin in those patients with cardiac T2* <10 ms and between 10-20 ms. Similar cardiac findings have also been reported by other researchers [4]. Although the sample size is small, this study adds that for Indian population, deferasirox is a safe and efficacious iron chelator without any significant adverse effect even with doses of >30 mg/kg/day. Thus, the data shows promising results of deferasirox on cardiac iron and quantifies myocardial iron by non-invasive method. Presently, many thalassemia centers monitor cardiac iron with T2 weighted MRI imaging, but routine application of this technology has not been implemented across all centers.

Funding: None; Competing interests: None stated.

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4. Pathare A, Taher A, Daar S. Deferasirox (Exjade ®) significantly improves cardiac T2* in heavily iron overload patients with â thalassemia major. Ann Hematol. 2010,89:405-9.

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6. Pepe A, Meloni A, Capra M, Clanciulli P, Prossomariti L, Malaventura C, et al. Deferasirox, deferiprone and desferoxamine treatment in thalasemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging. Haematologica. 2011;96:41-7.