地拉罗司治疗重型β-地中海贫血铁过载患儿临床疗效及安全性研究

目的：探讨铁螯合剂地拉罗司（deferasirox，DFX）治疗重型β-地中海贫血（β-thalassemia major，β-TM）铁过载患儿的疗效及安全性。方法随机选择24例规律输血的β-TM铁过载患儿，参加DFX不同服药剂量的临床研究，调查血清铁蛋白（SF）的变化及不良反应。并将持续服用DFX 5年患儿与同期使用去铁胺联合去铁酮治疗患儿（对照组）的心脏MRI T2*、肝脏MRI T2*值进行比较。结果DFX每日20～30 mg/kg的起始剂量对于铁过载患儿无明显效果，加量至每日30～40 mg/kg 后SF水平下降显著(U=58，P＜0.01)；不良反应以血清肝脏转氨酶升高最为常见，其次为血清肌酐非进行性升高。持续DFX 治疗5年组SF水平明显低于对照组（1748±481 ng/mL vs 3462±1744 ng/mL，P<0.05）；肝脏MRI T2* 值明显高于对照组（8.5±2.9 ms vs 2.7±1.9 ms，P<0.01）。两组心脏MRI T2*均值比较差异无统计学意义。结论DFX能显著降低β-TM 患儿SF水平，并显示出剂量依赖性变化；其对心脏铁负荷的减少未显示出明显优势，而对肝脏铁负荷的减低疗效显著。DFX治疗的不良反应以肝酶升高、血清肌酐非进行性升高为主。

Curative effects and safety of deferasirox in treatment of iron overload in children with β-thalassemia major

Objective To study the effectiveness and safety of deferasirox(DFX) in the treatment of iron overload in children with β-thalassemia major.Methods Twenty-four β-thalassemia major children with iron overload who received regular blood transfusion were randomly enrolled.The serum feritin(SF) levels were measured in the patients after different doses of DFX treatment.The DFX treatment-related adverse events were observed.The values of cardiac MRI T2* and liver MRI T2* were compared between the patients receiving DFX treatment for 5 years and the patients treated with deferoxamine and deferiprone.Results The patients with iron overload did not respond to DFX at the initial dose of 20-30 mg/kg·d.However,the SF level decreased significantly after the dose of DFX increased to 30-40 mg/kg·d(U=58,P<0.01).Serum liver transaminase elevation was the most common adverse effect,followed by non-progressive elevation in serum creatinine level.The mean SF level was significantly lower(1748±481 ng/mL vs 3462±1744 ng/mL;P<0.05),in contrast,the liver MRI T2* value was significantly higher(8.5±2.9 ms vs 2.7±1.9 ms;P<0.01) in patients receiving DFX treatment for 5 years than in the controls.There were no significant differences in the cardiac MRI T2* value between the two groups.Conclusions DFX can reduce SF levels in a dose-dependent manner in children with β-thalassemia major.It can significantly lower liver iron overload but not cardiac overload.Serum liver transaminase elevation and non-progressive elevation in serum creatinine level are major adverse effects in DFX treatment.