Reduction of body iron stores to normal range levels in thalassaemia by using a deferiprone/deferoxamine combination and their maintenance thereafter by deferiprone monotherapy

Abstract

Iron overload and toxicity is the major cause of morbidity and mortality in thalassaemia patients. New chelating drug protocols are necessary to treat completely transfusional iron overload and eliminate associated toxicity. Appropriate deferiprone/deferoxamine combinations could achieve this goal. A single-centre, single-armed, proof-of-concept study of the combination of deferiprone (75-100 mg/kg/d) and deferoxamine (40-60 mg/kg, at least 3 d per week) was carried out in eight patients with thalassaemia major (four men and four women) for 21-68 months. The patients were previously treated with deferoxamine and had variable serum ferritin [geometric (G) mean ± SD = 1446 ± 1035 μg/L] and magnetic resonance imaging relaxation times T2* cardiac (Gmean ± SD = 10.32 ± 6.72 ms) and liver (G mean ± SD = 3.77 ± 4.69 ms). The use of deferiprone (80-100 mg/kg/d) continued for 7-26 months in seven of the eight patients following the combination therapy. Organ function, blood and other biochemical parameters were monitored for toxicity. The deferiprone/deferoxamine combination caused an absolute value increase in cardiac (G mean ± SD = 29.6 ± 6.6 ms, P < 0.00076) and liver (G mean ± SD = 25.9 ± 8.07 ms, P < 0.00075) T2* and reduction in serum ferritin (G mean ± SD = 114.7 ± 139.8 μg/L, P < 0.0052) to within the normal body iron store range levels. In two cases, normalisation was achieved within a year. Deferiprone monotherapy was sufficient thereafter in maintaining normal range cardiac (G mean ± SD = 31.4 ± 5.25 ms, P < 0.79) and liver (G mean ± SD = 26.2 ± 12.4 ms, P < 0.58) T2* and normal serum ferritin (G mean ± SD = 150.7 ± 159.1, μg/L, P < 0.17) in five of the seven patients. No serious toxicity was observed. Transfusional iron overload in patients with thalassaemia could be reduced to normal body iron range levels using effective deferiprone/deferoxamine combinations. These levels could be maintained using deferiprone monotherapy.