Successful chelation therapy with the combination of deferasirox and deferiprone in a patient with thalassaemia major and persisting severe iron overload after single‐agent chelation therapies

Iron overload occurs commonly in patients with beta-thalassaemia major (TM) mainly as a result of the frequent blood transfusions. Without adequate iron chelation therapy, almost all patients will accumulate potentially fatal iron levels that are toxic to the heart, liver and endocrine glands. Deferoxamine has been the standard of care for transfusional iron overload for more than 40 years, although subcutaneous infusion negatively affects patient compliance (Delea et al, 2007). The oral iron chelators, deferiprone and deferasirox, are effective in reducing iron burden, while at the same time they improve compliance and patients’ quality of life (Cappellini et al, 2006; Roberts et al, 2007). Combinations of one oral chelator with deferoxamine have been used to increase the efficacy and induce negative iron balance in some patients with severe iron overload (Galanello et al, 2010). However, there are very limited data in the literature for effective combinations of two oral chelators. We report here a case of TM who had refractory severe iron overload and was successfully chelated with the combination of the two available oral agents, deferiprone and deferasirox. A 34-year-old female with beta TM (IVSI-110/IVSI-110) had been regularly transfused with two units of packed red blood cell, every 20 d, from the age of 2 years. The patient was put on chelation therapy with deferoxamine but the she failed to comply with the treatment. Given that the liver and cardiac magnetic resonance imaging (MRI) T2* were 1Æ11 and 9Æ36 ms respectively (both indicative of severe iron overload; normal values of heart T2* are >20 ms) and serum ferritin was persistently more than 2800 lg/l, the patient started on deferasirox, in 2006. MRI was performed as previously described (Voskaridou et al, 2004). The patient was started on deferasirox, at a dose of 20 mg/ kg/d, without major improvement of her iron overload status. The liver and cardiac MRI T2* were 3Æ33 ms and 10Æ59 ms respectively, after 12 months of treatment (Fig 1A). Thus, deferasirox dose was increased to 30 mg/kg/d and the patient was routinely followed up. Two years later, serum ferritin was persistently high (2080 lg/l; Fig 1B). Liver and cardiac MRI T2* values (7Æ81 and 13Æ76 ms respectively) were still compatible with moderate liver and severe heart siderosis, although there was improvement from the baseline values of 3 years earlier (Fig 1A). Due to the continuously elevated serum ferritin, the persistence of moderate liver and cardiac overload and the presence of a severe episode of atrial fibrillation 3Æ2 years post-deferasirox initiation, it was suggested that the patient started combined chelation therapy with both deferasirox and deferiprone. After giving written consent, the patient received therapy with a combination of the two