Pilot study of vascular health in survivors of Hodgkin lymphoma

Background: Vascular-related toxicities have been reported among survivors of Hodgkin lymphoma (HL), but their genesis is not well understood. Procedure: Fasting blood samples from 25 previously irradiated HL survivors were analyzed for biomarkers that can reveal underlying inflammation and/or endothelial cell activation: high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and vascular cell adhesion molecule-1 (VCAM-1) expression. Values were compared to subjects in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CECs and VCAM-1 were compared to healthy controls. Results: Survivors (76% male), median age 17.6 years (5-33) at diagnosis, 33.0 years (19-55) at follow-up, included stages IA (n=6), IIA (n=10), IIB (n=2), IIIA (n=4), and IVA (n=3) patients. Twenty-four received at least chest radiation therapy (RT) (median dose 3,150 cGy; range: 175-4,650 cGy), one received neck only; 14 (56%) had a history of anthracycline exposure (median dose: 124mg/m ² range: 63-200mg/m2). Compared to CARDIA subjects, mean hsCRP (3.0mg/L±2.0 vs. 1.6±1.9), total cholesterol (194.1mg/dl±33.2 vs. 179.4±32.9), lipoprotein (a) (34.2mg/dl±17.5 vs. 13.8±17.5), and fibrinogen (342.0mg/dl±49.1 vs. 252.6±48.4) were significantly elevated. CECs (2.3 cells/ml±1.5 vs. 0.34±1.4) were significantly elevated compared to controls. No difference in VCAM-1 expression (51.1%±36.8 vs. 42.3±35.6) was detected. Conclusion: HL survivors exposed to RT have evidence of vascular inflammation, dyslipidemia, and injury suggestive of early atherogenesis.