Jackson Rosanna K, Irving Julie A E, Veal Gareth J
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
Br J Haematol. 2016 Apr;173(1):13-24. doi: 10.1111/bjh.13924. Epub 2016 Jan 5.
Dexamethasone is a key component in the treatment of childhood acute lymphoblastic leukaemia (ALL). Despite playing a key role in the improved survival of ALL over several decades, intensification of dexamethasone therapy has also contributed to the increased toxicity associated with treatment, which is now seen to be at unacceptable levels given the favourable disease prognosis. Therefore the focus for treatment is now shifting towards reducing toxicity whilst maintaining current survival rates. As approximately 50% of patients were successfully treated on less intensive protocols of the 1980s, it has been questioned whether therapy intensification is necessary in all patients. Furthermore, there remains a subset of children who are still not cured of their disease. New strategies are therefore needed to identify patients who could benefit from dose reduction or intensification. However, adjusting a potentially life threatening therapy is a challenging task, particularly given the heterogeneous nature of ALL. This review focuses on the potential for patient stratification based on our current knowledge of dexamethasone pharmacokinetics, pharmacogenetics and the action of dexamethasone at the cellular level. A carefully designed, combined approach is needed if we are to achieve the aim of improved personalization of dexamethasone therapy for future patients.
地塞米松是儿童急性淋巴细胞白血病（ALL）治疗中的关键组成部分。尽管在过去几十年中，地塞米松对提高ALL患者的生存率起到了关键作用，但强化地塞米松治疗也导致了与治疗相关的毒性增加，鉴于疾病预后良好，目前这种毒性已达到不可接受的水平。因此，治疗重点现在正转向在维持当前生存率的同时降低毒性。由于20世纪80年代约50%的患者通过强度较低的方案得到了成功治疗，人们质疑是否所有患者都需要强化治疗。此外，仍有一部分儿童的疾病尚未治愈。因此，需要新的策略来识别那些可能从剂量减少或强化中获益的患者。然而，调整一种可能危及生命的治疗方法是一项具有挑战性的任务，特别是考虑到ALL的异质性。本综述基于我们目前对地塞米松药代动力学、药物遗传学以及地塞米松在细胞水平上的作用的了解，重点探讨患者分层的可能性。如果我们要实现为未来患者改善地塞米松治疗个性化的目标，就需要精心设计的综合方法。
