Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases.

ABSTRACT

In the last few years we have witnessed the emergence of oral chelation which is a new form of therapy for transfusional iron-loaded patients in thalassaemia and other refractory anaemias. The need for a cheap, non-toxic, orally effective iron chelator is paramount because it could potentially save the lives of many thousands of patients. At present, less than 10% of the patients requiring iron chelation therapy worldwide receive the widely used chelating drug desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or INN Deferiprone), which has so far been taken by over 450 patients in 15 countries, and in some cases daily for over 4 years with very promising results. L1 was shown at 50-100 mg/kg/day to be effective in bringing patients to negative iron balance. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic side effects were mainly encountered at high doses (80-100 mg/kg/day) and include transient agranulocytosis (5 cases), transient musculoskeletal and joint pains (10-20%), gastric intolerance (2-6%) and zinc deficiency (1%). The incidence of these toxic side effects was reduced by using lower doses of 50-75 mg/kg/day. The overall efficacy and toxicity of L1 is comparable to that of DF in animals and humans. Further work is required for identifying susceptible individuals to L1 toxicity, and also optimum dose protocols of L1 which can maximise iron excretion and minimise the incidence of toxic side effects.