University College London, London, United Kingdom.
Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361.
Transfusion combined with chelation therapy for severe β thalassemia syndromes (transfusion-dependent thalassemia [TDT]) has been successful in extending life expectancy, decreasing comorbidities and improving quality of life. However, this puts lifelong demands not only on the patients but also on the health care systems that are tasked with delivering long-term treatment and comprehensive support. Prevention programs and curative approaches are therefore an important part of overall strategy. Curative treatments alter the dynamic of a patient's health care costs, from financial commitment over 50 years, into a potential "one-off" investment. Since the 1980s, this has usually been available only to the 30% or so of young children with matched sibling donors. By improving the safety of matched related donors and haploidentical hematopoietic stem cell transplants, the potential size of the donor pool for curative therapies may be increased. Recent advances in gene therapy demonstrate that even patients lacking a matched donor can be rendered transfusion independent with an autograft of genetically modified autologous stem cells, with a low short-term risk. Noncurative treatments are also of potential value by decreasing use of blood and chelators and decreasing hospital visits. An example is luspatercept, an activin-receptor trap that modifies transforming growth factor-β signaling, thereby increasing the efficiency of erythropoiesis. This has entered phase 3 clinical trials for TDT and non-TDT and, usefully increases in both Hb and quality of life in non-TDT as well as decreasing transfusion requirements in TDT. Other novel noncurative treatments are entering clinical trials such improvement of erythropoiesis through pharmacological manipulation of hepcidin and iron metabolism.
输血联合螯合疗法治疗严重β地中海贫血综合征（输血依赖型地中海贫血[TDT]）已成功延长了预期寿命，减少了合并症并提高了生活质量。然而，这不仅对患者，而且对负责提供长期治疗和全面支持的医疗保健系统都提出了终身需求。因此，预防计划和治疗方法是整体策略的重要组成部分。治疗方法改变了患者医疗费用的动态，从 50 多年的财务承诺转变为潜在的“一次性”投资。自 20 世纪 80 年代以来，这通常仅适用于有匹配兄弟姐妹供体的 30%左右的年幼儿童。通过提高匹配相关供体和单倍体造血干细胞移植的安全性，治疗性疗法的供体库的潜在规模可能会扩大。基因治疗的最新进展表明，即使没有匹配供体的患者也可以通过自体基因修饰的自体干细胞移植实现输血独立性，并且短期风险较低。非治疗方法也具有潜在的价值，可以减少血液和螯合剂的使用并减少住院次数。例如，luspatercept 是一种激活素受体陷阱，可调节转化生长因子-β信号，从而提高红细胞生成效率。它已进入 TDT 和非 TDT 的 3 期临床试验，并且在非 TDT 中既可以增加 Hb 又可以提高生活质量，同时减少 TDT 的输血需求。其他新型非治疗方法也正在进入临床试验，例如通过药理学手段操纵铁调素和铁代谢来改善红细胞生成。
