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骨髓纤维化中的贫血:当前及新出现的治疗选择

Anemia in myelofibrosis: Current and emerging treatment options.

作者信息

Passamonti Francesco, Harrison Claire N, Mesa Ruben A, Kiladjian Jean-Jacques, Vannucchi Alessandro M, Verstovsek Srdan

机构信息

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Guy's and St. Thomas' NHS Foundation Trust, London, UK.

出版信息

Crit Rev Oncol Hematol. 2022 Dec;180:103862. doi: 10.1016/j.critrevonc.2022.103862. Epub 2022 Nov 1.

Abstract

Myelofibrosis (MF) is a clonal hematologic malignancy with progressive bone marrow fibrosis. Clinical manifestations of MF include splenomegaly, constitutional symptoms, and anemia, whose pathogenesis is multifactorial and largely due to ineffective erythropoiesis and is clinically associated with poor quality of life and reduced overall survival. The only curative treatment for MF is allogenic stem cell transplantation; however, few patients are eligible. Disease management strategies for MF-related anemia have limited effectiveness, and Janus kinase (JAK) inhibitors may induce or worsen related anemia. Thus, there is a significant unmet need for the treatment of patients with MF-related anemia. This review summarizes current and emerging treatments for anemia in MF, including luspatercept and KER-050 (transforming growth factor-β ligand traps), momelotinib and pacritinib (JAK inhibitors), pelabresib (a bromodomain extra-terminal domain inhibitor), PRM-151 (an antifibrotic agent), imetelstat (a telomerase inhibitor), and navitoclax (a BCL-2/BCL-xL inhibitor). Therapeutic combinations with ruxolitinib may offer another treatment approach.

摘要

骨髓纤维化(MF)是一种伴有进行性骨髓纤维化的克隆性血液系统恶性肿瘤。MF的临床表现包括脾肿大、全身症状和贫血,其发病机制是多因素的,主要归因于无效的红细胞生成,并且在临床上与生活质量差和总生存期缩短相关。MF唯一的治愈性治疗方法是异基因干细胞移植;然而, eligible的患者很少。MF相关性贫血的疾病管理策略效果有限,且JAK抑制剂可能会诱发或加重相关贫血。因此,治疗MF相关性贫血的患者存在重大的未满足需求。本综述总结了MF中贫血的现有和新兴治疗方法,包括罗特西普和KER-050(转化生长因子-β配体陷阱)、莫洛替尼和帕西替尼(JAK抑制剂)、派拉布瑞西(一种溴结构域额外末端结构域抑制剂)、PRM-151(一种抗纤维化药物)、艾美司他(一种端粒酶抑制剂)和纳维托克司(一种BCL-2/BCL-xL抑制剂)。与芦可替尼的治疗联合可能提供另一种治疗方法。 (注:原文中“few patients are eligible”里“eligible”未翻译完整,可补充完整相关语义,比如“符合条件的”)

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