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在临床实践中管理JAK抑制剂治疗骨髓纤维化的副作用。

Managing side effects of JAK inhibitors for myelofibrosis in clinical practice.

作者信息

Saeed Iram, McLornan Donal, Harrison Claire N

机构信息

a Department of Haematological Medicine , King's College Hospital NHS Foundation Trust , London , UK.

b Department of Haematology , Guy's and St Thomas' NHS Foundation Trust , London , UK.

出版信息

Expert Rev Hematol. 2017 Jul;10(7):617-625. doi: 10.1080/17474086.2017.1337507. Epub 2017 Jun 19.

DOI:10.1080/17474086.2017.1337507
PMID:28571503
Abstract

Myelofibrosis (MF) is characterized by bone marrow fibrosis, abnormalities in peripheral counts, extramedullary hematopoiesis, splenomegaly and an increased risk of transformation to acute myeloid leukaemia. The disease course is often heterogeneous and management can range from observation alone through to allogeneic stem cell transplantation. As of 2017, the only approved medication for MF remains the JAK Inhibitor (JAKi), ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland; Incyte, Wilmington, Detroit, USA) although several others have reached advanced stages of clinical trials. Areas covered: In this review, we focus on the management of both common and uncommon side effects arising from the use of currently approved and clinical trial JAKi. Most of the discussion concerns ruxolitinib although we also cover both pacritinib (CTI BioPharma) and momelotinib (Gilead Sciences, Foster City, California) which have been in recent large, multinational phase III trials. The various approaches to management of JAKi-related side effects are discussed - with particular emphasis to anaemia, thrombocytopaenia and infection risk. Expert commentary: JAK inhibitors are effective in many individuals with MF and have revolutionized the current treatment paradigm. The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications.

摘要

骨髓纤维化(MF)的特征为骨髓纤维化、外周血细胞计数异常、髓外造血、脾肿大以及转化为急性髓系白血病的风险增加。疾病进程通常具有异质性,治疗方法可从单纯观察到异基因干细胞移植。截至2017年,唯一获批用于MF的药物仍是JAK抑制剂(JAKi)鲁索替尼(瑞士巴塞尔诺华制药公司;美国底特律威尔明顿因赛特公司),尽管其他几种药物已进入临床试验后期阶段。涵盖领域:在本综述中,我们重点关注使用当前获批的及处于临床试验阶段的JAKi所产生的常见和罕见副作用的管理。大部分讨论涉及鲁索替尼,不过我们也涵盖了帕西替尼(CTI生物制药公司)和莫洛替尼(加利福尼亚州福斯特城吉利德科学公司),这两种药物近期已进入大型跨国III期试验。本文讨论了管理JAKi相关副作用的各种方法,特别强调了贫血、血小板减少和感染风险。专家评论:JAK抑制剂对许多MF患者有效,彻底改变了当前的治疗模式。在大多数情况下,副作用情况是可预测的,通过高度的临床监测和剂量调整是可控制的。

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