Department of Hematology, Jagiellonian University Medical College, Kraków, Poland
Doctoral School in Medical Sciences and Health Sciences, Jagiellonian University Medical College, Kraków, Poland
Pol Arch Intern Med. 2024 Jun 27;134(6). doi: 10.20452/pamw.16719. Epub 2024 Apr 3.
Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML), but are endowed with negative effects on endothelial function.
We aimed to characterize endothelial function in patients with CML treated with various TKIs.
A total of 48 patients diagnosed with chronic‑phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow‑mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH‑PAT) and flow‑mediated skin fluorescence (FMSF).
Reactive hyperemia index, FMD, reactive hyperemia response (RHR), normoxia oscillatory index, and hyperemic response index did not differentiate between the group of patients with low / moderate risk in the Systematic Coronary Risk Estimation 2 (SCORE2), SCORE2‑Older Persons (SCORE2‑OP), and those with high / very high risk scores. Among the patients with low / intermediate risk based on the SCORE2 algorithm, some had lower (below the first quartile) values of the endothelial parameters, reflecting impaired endothelial function, as compared with the high / very high risk patient population. Lower values of the endothelial function parameters were associated with overall long‑term treatment with TKIs or ponatinib. Importantly, endothelial function assessed by FMSF (RHR) negatively correlated with total duration of TKI treatment, also after adjustment for age.
Endothelial function in CML patients treated with TKIs was not related to cardiovascular risk based on SCORE2/SCORE2‑OP algorithms but correlated with CML‑specific factors, including duration of TKI treatment. FMSF‑based assessment of skin microcirculation was a sensitive method for detecting the vascular effects of TKIs.
酪氨酸激酶抑制剂 (TKI) 彻底改变了慢性髓性白血病 (CML) 的治疗方法，但也对内皮功能产生了负面影响。
我们旨在描述接受各种 TKI 治疗的 CML 患者的内皮功能。
共纳入 48 例接受 TKI（如伊马替尼、博舒替尼、尼洛替尼、帕纳替尼和 ASCiminib）治疗的慢性期 CML 患者。通过血流介导的扩张 (FMD)、反应性充血外周动脉张力计 (RH-PAT) 和血流介导的皮肤荧光 (FMSF) 评估肱动脉和微血管内皮功能。
反应性充血指数、FMD、反应性充血反应 (RHR)、常氧振荡指数和充血反应指数在 SCORE2 低/中危组、SCORE2-老年人 (SCORE2-OP) 和高/极高危评分组的患者之间没有差异。在基于 SCORE2 算法的低/中危患者中，与高/极高危患者人群相比，一些患者的内皮参数值较低（低于第一四分位数），表明内皮功能受损。内皮功能参数值较低与整体长期 TKI 治疗或 ponatinib 治疗相关。重要的是，通过 FMSF（RHR）评估的内皮功能与 TKI 治疗的总持续时间呈负相关，即使在调整年龄后也是如此。
接受 TKI 治疗的 CML 患者的内皮功能与基于 SCORE2/SCORE2-OP 算法的心血管风险无关，但与包括 TKI 治疗持续时间在内的 CML 特异性因素相关。基于 FMSF 的皮肤微循环评估是检测 TKI 血管作用的敏感方法。
