通过使用地拉罗司/去铁胺联合治疗将地中海贫血患者的体内铁储存降低到正常范围水平，并此后通过地拉罗司单药治疗维持这一水平。

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

机构信息

Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus.

出版信息

Eur J Haematol. 2010 Nov;85(5):430-8. doi: 10.1111/j.1600-0609.2010.01499.x.

DOI:10.1111/j.1600-0609.2010.01499.x

PMID:20662901

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

铁过载和毒性是导致地中海贫血患者发病和死亡的主要原因。需要新的螯合药物方案来治疗完全输血引起的铁过载并消除相关毒性。适当的地拉罗司/去铁胺联合治疗可能实现这一目标。

方法

在 8 名男性和 4 名女性重型地中海贫血患者中进行了一项单中心、单臂、概念验证研究，评估地拉罗司（75-100mg/kg/d）和去铁胺（40-60mg/kg，每周至少 3 天）联合治疗 21-68 个月。这些患者之前接受过去铁胺治疗，血清铁蛋白水平（几何均数±标准差=1446±1035μg/L）和心脏（几何均数±标准差=10.32±6.72ms）和肝脏（几何均数±标准差=3.77±4.69ms）磁共振成像弛豫时间 T2*值存在差异。在联合治疗后，8 名患者中有 7 名继续使用地拉罗司（80-100mg/kg/d）治疗 7-26 个月。监测器官功能、血液和其他生化参数以评估毒性。

结果

地拉罗司/去铁胺联合治疗导致心脏（几何均数±标准差=29.6±6.6ms，P<0.00076）和肝脏（几何均数±标准差=25.9±8.07ms，P<0.00075）T2绝对值增加，并使血清铁蛋白水平（几何均数±标准差=114.7±139.8μg/L，P<0.0052）降低至正常体内铁储存范围。在 2 例患者中，一年内达到正常水平。此后，地拉罗司单药治疗足以维持心脏（几何均数±标准差=31.4±5.25ms，P<0.79）和肝脏（几何均数±标准差=26.2±12.4ms，P<0.58）T2和血清铁蛋白水平正常（几何均数±标准差=150.7±159.1μg/L，P<0.17）。在 7 名患者中有 5 名未观察到严重毒性。