Overview of current chelation practices

Abstract

Deferoxamine (DFO) is reference standard therapy for transfusional iron overload since the 1980s. Although it is a highly effective iron chelator, the compliance problem to subcutaneous administration of DFO remains as the major problem. The oral chelator Deferiprone (DFP) has no marketing licence in North America, however, it has been licensed in India since 1994 and the European Union (EU) granted marketing approval for DFP in 1999, specifically for patients with thalassemia major when DFO is inadequate, intolerable or unacceptable. There are still limited data available on the use of DFP in children between 6 and 10 years of age, and no data on DFP use in children under 6 years of age. Subsequently the oral chelator Deferasirox (DFX) was approved by FDA and EMA for the treatment of patients with transfusional iron overload -older than 2 years of age- as first line therapy, in 2005 and 2006 respectively. The primary objective of iron chelation is to maintain body iron at safe levels at all times but once iron is accumulated, the objective of iron chelation is to reduce tissue iron to safe levels which is a slow process. The chelation regimen, dose and frequency of administration, of the chelator(s) are mainly determined based on body iron burden, presence of myocardial iron and the transfusional iron loading rate. A proper monitoring of chelation is of importance for measuring the response rate to a particular regimen and providing dose adjustments to enhance chelation efficacy and to avoid toxicity. Efficacy of a chelation regimen may exhibit individual variability resulting from factors such as absorbtion and metabolism of the chelator. Tolerability and compliance are also individual variables effecting the response to chelation. Understanding of advantages and limitations of chelators, accurately determining chelation needs of patients with iron overload and designing individualized chelation regimens with less toxicity but optimum efficacy, should provide long-term survival and quality of life for patients with iron loading anemias. The goal of this review is to summarize current concepts in iron chelation therapies based on the considerable amount of prospective data obtained by clinical studies. 去铁胺 （DFO）是自20世纪80年以来输血引起铁过载的参考标准疗法。 虽然它是一种高效的铁螯合剂，但是去铁胺皮下给药的遵从性问题依旧是主要问题。 口服螯合剂去铁酮（DFP）在北美没有销售许可证，但是，它在1994年获得印度许可，1999年欧洲联盟（EU）批准授予去铁酮销售许可证，特别是当去铁胺不足、无法忍受或无法接受时，去铁酮可用于重型地中海贫血患者。 还可获得关于在6岁至10岁之间的儿童身上使用去铁酮的有限数据，但是没有关于在6岁以下儿童身上使用去铁酮的数据。 随后美国食品和药品管理局（FDA）和欧洲药品管理局（EMA）分别在2005年和2006年批准口服螯合剂去铁酮作为第一疗法来治疗2岁以上输血引起铁过载的患者。 铁螯合的主要目的是将身体铁维持在安全水平，但一旦铁累积起来，铁螯合的目标是把组织铁降低到安全级别，这是一个缓慢的过程。 确定螯合剂的螯合方案、剂量和频率管理的主要依据是身体铁负担、心肌铁的状态和输血铁负载速率。 适当监控螯合对测量特殊方案的反应速率和提供计量调整来加强螯合效果和避免毒效尤其重要。 由于一些因素，诸如：螯合剂的吸收和代谢，螯合方案的效果可能呈现个别变化。 耐受性和遵从性也是影响螯合反应的个别变量。 了解螯合剂的优点和局限性，准确确定铁过载患者的螯合需求以及设计毒效更小但效果更优的个性化螯合方案，可以向铁过载贫血患者提供长期的生存和生活质量。 此次调研的目的是在临床研究获得的相当数量预期数据基础上，总结铁螯合疗法的当前概念。

Keywords

• thalassemia, oral chelators.