Thalassemia major between liver and heart: Where we are now.

The aim of the study was to assess the current state in terms of liver and heart iron overload as well as of liver and heart related morbidity and mortality in a large cohort of thalassemia patients. Myocardial iron loading was present in 28.9% patients, which was severe in 3.2%. Liver iron was normal in 9.3% and severe in 15%. The rate of cardiac deaths started to decrease between 2000 and 2003 and dropped significantly afterwards. The prescription of combination therapy soon after the hospital admission for decompensated heart failure was associated with a decrease in the short-term mortality. In 111 adult patients who underwent liver elastometry, 14 HCVRNA positive subjects and 2 HCVRNA negative, had stiffness values suggestive of cirrhosis. No cases of hepatocarcinoma were reported. Liver "iron free foci" occurred in a HCV negative patient and the occurrence of a malignant epithelioid hemangioendothelioma led to liver transplantation in another. The study suggests that a subset of patients continues to develop progressive hemosiderosis that may lead to cardiac disease and death. Beyond its key role in preventing myocardial iron overload, liver iron chelation is essential for hampering the onset of hepatic tumors, which may not be limited to hepatocarcinoma.

Impact of heart magnetic resonance imaging on chelation choices, compliance with treatment and risk of heart disease in patients with thalassaemia major.

This study aimed to verify the impact of heart magnetic resonance imaging on chelation choices and patient compliance in a single-institution cohort as well as its predictive value for heart failure and arrhythmias. Abnormal cardiac T2* values determined changes in treatment in most subjects. Heart T2* was confirmed to be highly predictive over 1 year for heart failure and arrhythmias. The choice of chelation regimens known to remove heart iron efficiently was not sufficient by itself to influence the risk. Compliance with treatment had a more remarkable role.

Combined therapy with deferiprone and desferrioxamine in thalassemia major.

BACKGROUND AND OBJECTIVES: Effective and convenient iron chelation remains one of the main targets of clinical management of thalassemia major. The combined treatment with desferrioxamine and deferiprone could have an increased chelation efficacy and sometimes allow drug doses and toxicity to be reduced and the number of days of desferrioxamine infusion to be decreased, improving compliance and quality of life. DESIGN AND METHODS: We used combined therapy with desferrioxamine and deferiprone to treat 79 patients with severe iron overload (serum ferritin higher than 3000 ng/mL) who had low compliance with subcutaneous desferrioxamine. RESULTS: Total therapy exposure was 201 patient-years. Three patients developed agranulocytosis and seven mild neutropenia. Other adverse effects were nausea, vomiting, abdominal pain, increased concentrations of liver transaminases and joint pain. The efficacy of combined therapy was evaluated in 64 patients treated for at least 12 months. Ferritin decreased from 5243+/-2345 to 3439+/-2446 ng/mL, p<0.001). Mean urinary iron excretion during combined therapy was double that with desferrioxamine or deferiprone monotherapy. In 20 patients receiving heart therapy at baseline, left ventricular ejection fraction increased from 48.6+/-9% to 57+/-6% (p=0.0001) over 12 to 57 months, without modifying the cardiac treatment. INTERPRETATION AND CONCLUSIONS: Continuous deferiprone treatment with intermittent administration of subcutaneous desferrioxamine is a practical and effective procedure to decrease severe iron overload in patients with thalassemia major. This study also shows that the combined therapy is associated with an improvement in heart function.