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酪氨酸激酶抑制剂长期治疗慢性髓性白血病的疗效和心血管不良事件:长崎 CML 研究组报告。

Efficacy and Cardiovascular Adverse Events of Long-term Treatment with Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia: A Report from the Nagasaki CML Study Group.

机构信息

Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Department of Hematology, Nagasaki University Hospital, Japan.

出版信息

Intern Med. 2021 Jul 15;60(14):2207-2216. doi: 10.2169/internalmedicine.6620-20. Epub 2021 Feb 22.

Abstract

Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs. Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs. Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.0-4.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment. Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a "real-world" setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.

摘要

目的

慢性髓性白血病(CML)的标准治疗方法是持续使用酪氨酸激酶抑制剂(TKI),这使得大多数患者预后良好。最近的研究已经确定心血管疾病(CVDs)是与 TKI 相关的晚期不良事件(AE)。在这项研究中,我们评估了 TKI 的长期疗效和 AE,重点关注 CVDs。

方法

我们对长崎县接受 TKI 治疗的 CML 患者(2001 年至 2016 年确诊)进行了回顾性调查。临床数据来自他们的病历。我们分析了 TKI 治疗的 CML 患者的生存情况、估计 CVD 累积发生率以及 CVD 的危险因素。

结果

264 例接受 TKI 治疗(中位年龄 58 岁)的 CML 患者的总生存率为 89.6%(95%置信区间[CI],84.9-92.9%),分别在 CML 诊断后 5 年和 10 年时为 80.5%(95% CI,73.4-85.9%)。26 例(9.8%,中位年龄 67.5 岁)患者发生 CVD 事件,TKI 治疗中位时间为 65.5 个月。2 年和 5 年的累积发生率分别为 2.4%(95% CI,1.0-4.8%)和 5.2%(95% CI,2.8-8.6%)。CML 诊断时高血压和高 SCORE 图表风险与 TKI 治疗期间的 CVD 事件相关。

结论

在“真实世界”环境中,TKI 治疗有助于长崎县 CML 患者的长期生存,但这些患者 CVD 的发病率似乎有所增加。需要采取适当的方法来管理 CVD 的危险因素,以减少 TKI 治疗期间的 CVD 事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be5/8355380/45dedb4cdde7/1349-7235-60-2207-g001.jpg

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