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

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

[Article in Chinese]
S Yang  1 , Y Z Qin  1 , Y Y Lai  1 , H X Shi  1 , Y Hou  1 , X J Huang  1 , Q Jiang  1
Affiliations

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

[Article in Chinese]
S Yang et al. Zhonghua Xue Ye Xue Za Zhi. .

Abstract
in English, Chinese

Objective: To explore dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia (CML) . Methods: 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. Results: 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, HR=1.6; P<0.001) , advanced phase when starting dasatinib therapy (HR=2.2; P=0.008) , and cardiovascular comorbidity (ies) (HR=1.9; P=0.018) were significantly associated with developing PE. The advanced phase when starting dasatinib therapy (HR=3.4; P=0.001) , interval from diagnosis to taking TKI for ≤6 months (HR=2.2; P=0.015) , and dose < 100 mg/d when PE was found (HR=3.1; P=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. Conclusion: 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.

目的： 探索慢性髓性白血病（CML）患者接受达沙替尼治疗中肺部不良反应的发生率、影响因素及治疗转归。 方法： 回顾性分析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患者胸腔积液（PE）和肺动脉高压（PAH）的发生情况。 结果： 共纳入280例患者，中位达沙替尼治疗时间26（1~142）个月，发现PE 90例（32.1%），其中1级40例（44.4%），2级44例（48.9%），3级6例（6.7%）。PE发生率随服药时间延长逐渐升高，多因素分析结果显示，年龄增加（每增加10岁，HR=1.6，P<0.001）、服用达沙替尼时处于进展期（HR=2.2，P=0.008）和有心血管疾病合并症（HR=1.9，P=0.018）与PE发生显著相关。服用达沙替尼时处于进展期（HR=3.4，P=0.001）、确诊至开始服用酪氨酸激酶抑制剂时间≤6个月（HR=2.2，P=0.015）、发现PE时剂量<100 mg/d（HR=3.1，P=0.001）者PE程度更重。经减停达沙替尼、利尿、胸腔穿刺或置管等干预，半数患者PE减少或消失。减量服用达沙替尼的患者中，绝大多数可维持原治疗反应。在有咳嗽、胸闷或气促等症状的60例患者中，49例接受超声心动图（UCG）检查，8例（16.3%）发现PAH高度可能性，约占所有患者中的3.5%，其中6例（75.0%）合并PE，PAH为可逆性。原研与国产达沙替尼的PE和PAH发生率差异无统计学意义（P>0.05）。 结论： 在服用达沙替尼的CML患者中，PE是常见的不良反应，PAH较少见，应注意识别高危人群、密切监测和及时干预。.

Keywords: Dasatinib; Leukemia, myelogenous, chronic, BCR-ABL positive; Pleural effusion; Pulmonary artery hypertension.

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Figures

图1
图1. 国产与原研达沙替尼治疗组（各56例）胸腔积液、转换治疗方式累计发生率比较
See this image and copyright information in PMC

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