Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System and College of Pharmacy, 1111 E. Catherine St., Ann Arbor, MI 48109, USA.
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan C.S. Mott Children's Hospital, 1540 E Hospital Dr, Ann Arbor, MI 48109, USA.
Blood Rev. 2017 Sep;31(5):328-338. doi: 10.1016/j.blre.2017.06.002. Epub 2017 Jul 5.
Asparaginase remains a cornerstone of ALL therapy and is one of the key contributing factors to improved outcomes in adolescent and young adult (AYA) patients treated on pediatric protocols. Asparagine depletion has been associated with improved outcomes in ALL patients; this has led to an increased emphasis on optimizing asparagine depletion in ALL patients of all ages. To ensure adequate asparagine depletion, the use of therapeutic drug monitoring of asparaginase therapy holds much promise, yet remains underutilized in practice. Data regarding asparaginase activity level monitoring and associated outcomes are reviewed, and an evidence-based asparaginase activity level monitoring algorithm is presented. Finally, unique management strategies for key asparaginase toxicities in ALL patients are discussed, as well as a discussion of novel asparaginase formulations on the horizon.
asparaginase 仍然是 ALL 治疗的基石，也是改善儿科方案治疗的青少年和年轻成人 (AYA) 患者治疗结果的关键因素之一。天冬酰胺耗竭与 ALL 患者的改善结果相关；这导致了在所有年龄段的 ALL 患者中更加重视优化天冬酰胺耗竭。为了确保足够的天冬酰胺耗竭，治疗药物监测 asparaginase 治疗具有很大的潜力，但在实践中仍未得到充分利用。审查了关于 asparaginase 活性水平监测和相关结果的数据，并提出了基于证据的 asparaginase 活性水平监测算法。最后，讨论了 ALL 患者中关键 asparaginase 毒性的独特管理策略，以及即将出现的新型 asparaginase 制剂的讨论。
