Morsani College of Medicine, University of South Florida, Tampa, FL.
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
JCO Precis Oncol. 2023 Sep;7:e2300208. doi: 10.1200/PO.23.00208.
The main dose-limiting toxicity of anthracyclines is cardiotoxicity. Clonal hematopoiesis (CH), somatic mutations in hematopoietic stem or progenitor cells in patients without hematologic malignancy, is also associated with risk for adverse cardiovascular events and worse outcomes overall. We hypothesize that CH increases risk for doxorubicin-induced cardiotoxicity (DIC).
We conducted a retrospective cohort study in patients treated with doxorubicin for cancer (N = 100). Patients (n = 25) had incident symptomatic heart failure, decline in left ventricular ejection fraction, or arrhythmia. CH was identified using paired peripheral blood and tumor DNA.
After adjusting for age at doxorubicin initiation, diabetes, dyslipidemia, and chest radiation, high cumulative dose of doxorubicin (>240 mg/m; odds ratio [OR], 7.00; 95% CI, 1.77 to 27.74; = .0056), CH (OR, 8.58; 95% CI, 2.05 to 35.99; = .0033), and history of smoking (OR, 3.15; 95% CI, 1.00 to 9.93; = .0495) were associated with DIC.
This study provides preliminary evidence for CH as a predictive risk factor for DIC, which, with further investigation, could serve as an important precision medicine biomarker for the large number of patients with cancer who have CH.
蒽环类药物的主要剂量限制毒性是心脏毒性。克隆性造血（CH），即无血液系统恶性肿瘤的患者造血干细胞或祖细胞中的体细胞突变，也与不良心血管事件风险增加和总体预后较差相关。我们假设 CH 增加了多柔比星引起的心脏毒性（DIC）的风险。
我们对接受多柔比星治疗癌症的患者（N=100）进行了一项回顾性队列研究。患者（n=25）出现症状性心力衰竭、左心室射血分数下降或心律失常。通过配对的外周血和肿瘤 DNA 鉴定 CH。
在调整了多柔比星起始年龄、糖尿病、血脂异常和胸部放疗后，高累积多柔比星剂量（>240mg/m；比值比[OR]，7.00；95%置信区间[CI]，1.77 至 27.74；P=.0056）、CH（OR，8.58；95%CI，2.05 至 35.99；P=.0033）和吸烟史（OR，3.15；95%CI，1.00 至 9.93；P=.0495）与 DIC 相关。
这项研究为 CH 作为 DIC 的预测风险因素提供了初步证据，如果进一步研究，CH 可能成为癌症患者中大量存在 CH 的重要精准医学生物标志物。
