Moreover, the treating haematologist will also ensure compliance to the chelation therapy. Chelation drug Potential adverse effects Deferoxamine

EtOH Deferoxamine may cause injection site reactions, systemic reactions (eg, abdominal pain, arthralgia, nausea, vomiting), cardiovascular reactions (eg, hypotension with too rapid IV infusion, tachycardia, shock), hypersensitivity reactions (eg, anaphylactic reaction with or without shock, angio-oedema, generalised rash, urticaria), haematological reactions (eg, thrombocytopaenia and leucopaenia), hepatic dysfunction, musculoskeletal reactions (eg, muscle spasms, growth retardation and bone changes including metaphyseal dysplasia are common in doses ≥60 mg/kg, especially those who begin iron chelation in the first 3 years of life; reduced risk if doses are kept to ≤40 mg/kg) and neurological disturbances (eg, dizziness, peripheral sensory, motor, or mixed neuropathy, paraesthesias, seizures; exacerbation or precipitation of aluminium-related dialysis encephalopathy), and respiratory reactions (eg, acute respiratory distress syndrome with dyspnoea, cyanosis and/or interstitial infiltrates) (chelation therapy protocol as per online supplementary appendix A or C and D). Deferasirox Deferasirox does not appear to present any increased overall burden in adverse effects when compared with placebo (chelation therapy

protocol as per online supplementary appendix A or C and D). When compared with deferoxamine, there is an absence of injection site effects, but an increase in GI effects, which occurs in about 15% of patients.

Other common effects include transient rises in serum creatinine, back pain and rash. The haematology team as per their standard clinical practice will deal with adverse effects and the cost incurred will also be borne by the patient. Study procedures and monitoring Eligible patients meeting the inclusion/exclusion criteria will be recruited over a 4-month period (following registration on clinicaltrials.gov). Each patient will be randomised into either of two study arms: amlodipine plus chelation or chelation alone. All patients will undergo the following Dacomitinib tests at baseline and at 6 and 12 month follow-up visits: Myocardial iron content using cardiac MRI and T2* imaging;27 32 Liver iron content using MRI and T2* imaging;27 32 Myocardial systolic function using standard measures (EF) and diastolic function using conventional and tissue Doppler imaging; Myocardial function using speckled tracking derived strain and strain rate analysis; Serum ferritin levels. The cost of the aforementioned investigations is budgeted through the grant except for the cost of the serum ferritin levels which will be borne by the patient. In addition, patients will receive standard care and have follow-up appointments as dictated by the chelation therapy.