Department of Internal Medicine I, Division of Hematology & Hemostaseology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria;
Department of Internal Medicine I, Division of Hematology & Hemostaseology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria; Department/Clinic for Companion Animals and Horses, Clinic for Small Animals, Clinical Unit of Internal Medicine, University of Veterinary Medicine Vienna, Vienna, Austria;
Blood. 2015 Feb 5;125(6):901-6. doi: 10.1182/blood-2014-09-594432. Epub 2014 Dec 18.
Vascular safety is an emerging issue in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Whereas imatinib exhibits a well-documented and favorable long-term safety profile without obvious accumulation of vascular events, several types of vascular adverse events (VAEs) have been described in patients receiving second- or third-generation BCR/ABL1 TKIs. Such VAEs include pulmonary hypertension in patients treated with dasatinib, peripheral arterial occlusive disease and other arterial disorders in patients receiving nilotinib, and venous and arterial vascular occlusive events during ponatinib. Although each TKI interacts with a unique profile of molecular targets and has been associated with a unique pattern of adverse events, the mechanisms of drug-induced vasculopathy are not well understood. Here, recent data and concepts around VAEs in TKI-treated patients with CML are discussed, with special reference to potential mechanisms, event management, and strategies aimed at avoiding occurrence of such events in long-term treated patients.
血管安全性是接受酪氨酸激酶抑制剂 (TKI) 治疗的慢性髓性白血病 (CML) 患者的一个新出现的问题。伊马替尼具有良好记录的、有利的长期安全性，没有明显的血管事件积累，然而，在接受第二代或第三代 BCR/ABL1 TKI 治疗的患者中已经描述了几种类型的血管不良事件 (VAEs)。这些 VAEs 包括接受达沙替尼治疗的患者中的肺动脉高压、接受尼洛替尼治疗的患者中的外周动脉闭塞性疾病和其他动脉疾病，以及在接受 ponatinib 治疗期间的静脉和动脉血管闭塞事件。虽然每种 TKI 与独特的分子靶标相互作用，并与独特的不良事件模式相关，但药物诱导性血管病变的机制尚不清楚。在这里，讨论了接受 TKI 治疗的 CML 患者中 VAEs 的最新数据和概念，特别参考了潜在机制、事件管理以及旨在避免长期治疗患者发生此类事件的策略。
