Department of Pediatrics, Division of Hematology/Oncology, Weill Cornell Medical College, New York, USA.
Curr Opin Hematol. 2019 May;26(3):139-144. doi: 10.1097/MOH.0000000000000499.
For individuals who have transfusion-dependent anemia, iron overload is the long-term complication, which results in significant morbidity. Ameliorating this is now the biggest unmet need. This review specifically addresses this issue.
Over the last decade or so, major advances in the treatment of these individuals, has resulted from novel strategies aimed at reducing transfusion requirement as well as optimizing chelation therapy. This review will summarize these advances and provide insights into some of the therapies in the pipeline. Strategies aimed at reducing transfusion requirement include modulation of erythropoietic regulation by reducing ineffective red cell production through activin trapping, as well as stem cell gene modification approaches, which aim for a cure, and transfusion independence. Refined means of assessing tissue iron and the introduction of oral chelators have facilitated tailoring chelation regimens with closer monitoring and improved compliance. Newer approaches to ameliorate iron toxicity have focused on the hepcidin pathway, all of which would result in increased hepcidin levels and reduction of iron absorption from the intestine, sequestration of iron in normal storage sites and reduced exposure of more susceptible organs, such as the heart and endocrine organs, to the toxic effects of increased iron.
These advances offer the promise of improved management of transfusion-dependent individuals.
对于依赖输血的贫血患者，铁过载是长期的并发症，会导致严重的发病率。改善这一点是目前最大的未满足需求。本综述专门讨论了这个问题。
在过去的十年左右，由于旨在减少输血需求和优化螯合疗法的新策略，这些患者的治疗取得了重大进展。本综述将总结这些进展，并深入探讨一些正在研发中的疗法。旨在减少输血需求的策略包括通过激活素捕获减少无效红细胞生成来调节红细胞生成的调节，以及旨在实现治愈和输血独立性的干细胞基因修饰方法。评估组织铁的更精细方法和口服螯合剂的引入促进了更密切监测和提高依从性的螯合方案的定制。改善铁毒性的新方法侧重于铁调素途径，所有这些方法都将导致铁调素水平升高，减少肠道对铁的吸收，将铁隔离在正常储存部位，并减少心脏和内分泌器官等更敏感的器官暴露于增加的铁的毒性作用。
这些进展为改善依赖输血的个体的管理提供了希望。
