Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major
Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major
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DOI：
10.1056/nejm199808133390701
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发表时间：
1998-08-13
影响因子：
158.5
通讯作者：
Fleming, KA
中科院分区：
文献类型：
--
作者：
Olivieri, NF;Brittenham, GM;Fleming, KA
背景去铁酮是一种口服活性铁螯合剂，正在评估其作为重型地中海贫血铁超载的治疗方法。动物模型研究表明，长期治疗与去铁酮疗效下降和肝纤维化加剧有关。方法每年通过肝活检标本的化学分析、磁敏感度测定法或两者同时测定肝铁储存量。三名不了解患者临床状况、获取标本时间和标本铁含量的肝脏病理学家检查了 19 名接受去铁酮治疗一年以上患者的 72 份活检标本。为了进行比较，对取自 20 名接受肠外去铁胺治疗超过一年的患者的 48 份肝活检标本进行了类似审查。结果 在 19 名接受去铁酮治疗的患者中，18 名患者连续接受该药物的平均时间 (+/-SE) 为 4.6+/-0.3 年。最终分析显示，18 例中有 7 例的肝铁浓度至少为每克肝脏湿重 80 μmol（高于该值，重型地中海贫血患者患心脏病和过早死亡的风险会增加）。在 19 名患者中，在一年多的时间里进行了多次活检，其中 14 名可以评估肝纤维化的进展；在 20 名接受去铁胺治疗的患者中，有 12 名可以进行进展评估。 5 名接受去铁酮治疗的患者出现纤维化进展，而接受去铁胺治疗的患者则没有出现纤维化进展（P=0.04）。通过生命表法，我们估计接受去铁酮治疗的患者至纤维化进展的中位时间为 3.2 年。调整初始肝铁浓度后，去铁酮治疗每增加一年，纤维化进展的估计几率就会增加 5.8 倍（95% 置信区间，1.1 至 29.6）。 结论 去铁酮不能充分控制地中海贫血患者的体内铁负荷，并可能加重肝纤维化。 （N Engl J Med 1998；339：417-23。）(C)1998，马萨诸塞州医学会。
Background Deferiprone is an orally active iron-chelation agent that is being evaluated as a treatment for iron overload in thalassemia major. Studies in an animal model showed that prolonged treatment is associated with a decline in the effectiveness of deferiprone and exacerbation of hepatic fibrosis.Methods Hepatic iron stores were determined yearly by chemical analysis of liver-biopsy specimens, magnetic susceptometry, or both. Three hepatopathologists who were unaware of the patients' clinical status, the time at which the specimens were obtained, and the iron content of the specimens examined 72 biopsy specimens from 19 patients treated with deferiprone for more than one year. For comparison, 48 liver-biopsy specimens obtained from 20 patients treated with parenteral deferoxamine far more than one year were similarly reviewed.Results Of the 19 patients treated with deferiprone, 18 had received the drug continuously for a mean (+/-SE) of 4.6+/-0.3 years. At the final analysis, 7 of the 18 had hepatic iron concentrations of at least 80 mu mol per gram of liver, wet weight (the value above which there is an increased risk of cardiac disease and early death in patients with thalassemia major). Of 19 patients in whom multiple biopsies were performed over a period of more than one year, 14 could be evaluated for progression of hepatic fibrosis; of the 20 deferoxamine-treated patients, 12 could be evaluated for progression. Five deferiprone-treated patients had progression of fibrosis, as compared with none of those given deferoxamine (P=0.04). By the life-table method, we estimated that the median time to progression of fibrosis was 3.2 years in deferiprone-treated patients. After adjustment for the initial hepatic iron concentration, the estimated odds of progression of fibrosis increased by a factor of 5.8 (95 percent confidence interval, 1.1 to 29.6) with each additional year of deferiprone treatment.Conclusions Deferiprone does not adequately control body iron burden in patients with thalassemia and may worsen hepatic fibrosis. (N Engl J Med 1998;339:417-23.) (C)1998, Massachusetts Medical Society.