Premature atherosclerosis after treatment for acute lymphoblastic leukemia in childhood

Abstract

Introduction: Late cardiovascular complications are the leading causes of morbidity and mortality in patients treated for common malignancies of childhood. Late cardiotoxicity include increased development of atherosclerosis and atherosclerosis - related diseases. An evaluation of the endothelium can be made based on the measurement of endothelium-derived blood vasoactive factors, such as cytokines and adhesion molecules. Their elevated serum levels may serve as sensitive indicators of early atherosclerotic lesions in high risk patients. Currently, assessment of common carotid intima-media thickness has emerged as one of the more powerful tools for evaluation of subclinical atherosclerosis. The purpose of this study was to compare these parameters between patients after antineoplatic treatment compared to persons not exposed to such factors.

Material and methods: Early progression of atherosclerotic disease was evaluated in 64 survivors treated for Acute Lymphoblastic Leukaemia (ALL) in childhood, and in a control group of 36 healthy volunteers. Blood serum concentrations of selected new biomarkers, indicative of endothelial damage and inflammatory activity, were measured, including intercellular adhesion molecule-1 (sICAM-1), endothelial leukocyte adhesion molecule-1 (E-selectin), thrombomodulin (TM), interleukin 6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The common carotid intima-media thickness (IMT) was also assessed via ultrasound examination.

Results: Significantly higher blood concentrations of sICAM-1 adhesive molecule (229.3±62.2 ng/mL vs. 199.9 ± 63.3 ng/ mL, p=0.0072) and IL-6 (2.1 ± 2.7 pg/mL vs. 1.9 ± 3.6 pg/mL, p=0.0414) were found in ALL survivors compared with control subjects. Concentration of hs-CRP was also higher in the ALL group: 1.3 ± 2.2 ug/mL vs. 0.6 ± 0.9 ug/mL. This difference was close to statistical significance (p=0.0599). The mean IMT values for right and left carotid arteries were higher in ALL patients after antineoplastic therapy, compared with healthy subjects (IMT-R 0.056±0.008 mm vs. 0.052±0.003 mm; p=0.0021; IMT-L 0.057±0.009 mm vs. 0.052±0.003 mm; p=0.0051).

Conclusions: Survivors of childhood ALL in the examined group demonstrated elevated concentrations of selected new biomarkers and increased IMT values, compared to controls, which may confirm the occurrence of endothelial injuries in blood vessels. This study indicates that subjects treated for childhood malignancy are at a higher risk of prematurely developing atherosclerosis.

Keywords: atherosclerosis; biomarkers; intima-media thickness; leukemia; nthracycline cardiotoxicity; survivors.