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[慢性髓性白血病患者中与达沙替尼相关的肺部不良事件]

[Dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia].

作者信息

Yang S, Qin Y Z, Lai Y Y, Shi H X, Hou Y, Huang X J, Jiang Q

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2020 Dec 14;41(12):1013-1019. doi: 10.3760/cma.j.issn.0253-2727.2020.12.008.

DOI:10.3760/cma.j.issn.0253-2727.2020.12.008
PMID:33445849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7840556/
Abstract

To explore dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia (CML) . We retrospectively analyzed the incidence of pleural effusion (PE) and pulmonary arterial hypertension (PAH) in patients with CML treated with dasatinib at Peking University People's Hospital from April 2008 to January 2020. A total of 280 patients were collected. The median dasatinib treatment time was 26 (1-142) months. Ninety (32.1%) patients developed PE, including 40 (44.4%) in grade 1, 44 (48.9%) in grade 2, and 6 (6.7%) in grade 3. The incidence of PE increased gradually with the prolongation of treatment. The multivariate analysis showed that increasing age (every 10 years, =1.6; <0.001) , advanced phase when starting dasatinib therapy (=2.2; =0.008) , and cardiovascular comorbidity (ies) (=1.9; =0.018) were significantly associated with developing PE. The advanced phase when starting dasatinib therapy (=3.4; =0.001) , interval from diagnosis to taking TKI for ≤6 months (=2.2; =0.015) , and dose < 100 mg/d when PE was found (=3.1; =0.001) were associated with more severe PE. PE relieved or disappeared after intervention in half of the patients. Among 60 patients with symptoms of cough, chest tightness, and shortness of breath, 49 underwent ultrasonic cardiography; 8 (16.3%) had high probability of PAH, approximately 3.5% in all patients; and 6 (75.0%) of them had PE. PAH was reversible. There was no difference in the incidences of PE and PAH between branded and Chinese generic dasatinib. PE is a common dasatinib-related pulmonary adverse event, and PAH is rare in patients with CML. The identification of individuals with high risk, close monitoring, and timely intervention may help to alleviate PE and PAH.

摘要

为探讨慢性髓性白血病(CML)患者中与达沙替尼相关的肺部不良事件。我们回顾性分析了2008年4月至2020年1月在北京大学人民医院接受达沙替尼治疗的CML患者中胸腔积液(PE)和肺动脉高压(PAH)的发生率。共收集了280例患者。达沙替尼的中位治疗时间为26(1 - 142)个月。90例(32.1%)患者发生PE,其中1级40例(44.4%),2级44例(48.9%),3级6例(6.7%)。PE的发生率随治疗时间延长而逐渐增加。多因素分析显示,年龄增加(每10岁,=1.6;<0.001)、开始达沙替尼治疗时处于晚期(=2.2;=0.008)以及有心血管合并症(=1.9;=0.018)与发生PE显著相关。开始达沙替尼治疗时处于晚期(=3.4;=0.001)、从诊断到开始服用酪氨酸激酶抑制剂(TKI)的间隔时间≤6个月(=2.2;=0.015)以及发现PE时剂量<100 mg/d(=3.1;=0.001)与更严重的PE相关。一半患者经干预后PE缓解或消失。在60例有咳嗽、胸闷和气短症状的患者中,49例接受了超声心动图检查;8例(16.3%)PAH可能性高,在所有患者中约为3.5%;其中6例(75.0%)有PE。PAH是可逆的。原研达沙替尼和国产达沙替尼在PE和PAH的发生率上无差异。PE是与达沙替尼相关的常见肺部不良事件,PAH在CML患者中罕见。识别高危个体、密切监测并及时干预可能有助于缓解PE和PAH。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d714/7840556/5de275c69577/cjh-41-12-1013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d714/7840556/5de275c69577/cjh-41-12-1013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d714/7840556/5de275c69577/cjh-41-12-1013-g001.jpg

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本文引用的文献

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European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia.欧洲白血病网络 2020 年治疗慢性髓性白血病的建议。
Leukemia. 2020 Apr;34(4):966-984. doi: 10.1038/s41375-020-0776-2. Epub 2020 Mar 3.
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[Chinese guidelines for the diagnosis and treatment of pulmonary hypertension 2018].《2018年中国肺动脉高压诊断与治疗指南》
Zhonghua Xin Xue Guan Bing Za Zhi. 2018 Dec 24;46(12):933-964. doi: 10.3760/cma.j.issn.0253-3758.2018.12.006.
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Clinical significance of dasatinib-induced pleural effusion in patients with de chronic myeloid leukemia.
达沙替尼诱发慢性髓性白血病患者胸腔积液的临床意义
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Haematologica. 2019 Jan;104(1):93-101. doi: 10.3324/haematol.2018.188987. Epub 2018 Aug 9.
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7
Pleural effusion and molecular response in dasatinib-treated chronic myeloid leukemia patients in a real-life Italian multicenter series.在意大利一项真实生活的多中心研究中,达沙替尼治疗慢性髓性白血病患者的胸腔积液与分子反应
Ann Hematol. 2018 Jan;97(1):95-100. doi: 10.1007/s00277-017-3144-1. Epub 2017 Oct 2.
8
Analysis of adverse events associated with dasatinib and nilotinib treatments in chronic-phase chronic myeloid leukemia patients outside clinical trials.在临床试验之外的慢性期慢性髓性白血病患者中,对与达沙替尼和尼洛替尼治疗相关的不良事件进行分析。
Int J Hematol. 2017 Aug;106(2):229-239. doi: 10.1007/s12185-017-2225-1. Epub 2017 Apr 4.
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Clin Lymphoma Myeloma Leuk. 2017 Feb;17(2):78-82. doi: 10.1016/j.clml.2016.09.012. Epub 2016 Sep 17.
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