BACKGROUND: Adult survivors of childhood acute lymphoblastic leukemia (ALL) have an earlier than expected mortality from cardiovascular disease. This study examined endothelial function in 75 young (age 30.2±7.1 y) adult survivors of childhood ALL who received chemotherapy without cranial radiation (n=25) or chemotherapy combined with cranial radiation (n=50) compared with a healthy control group of similar sex, age, and weight (n=59). PROCEDURE: As part of a clinical follow-up study, endothelial-dependent flow-mediated dilation (FMD: % change in artery diameter after 5 min of occlusion) was assessed using high-resolution ultrasound of the brachial artery. Fifteen minutes after the measurement of FMD, sublingual nitroglycerin (0.4 mg) was administered and the brachial artery was imaged using ultrasound to assess endothelial-independent dilation (EID). All ultrasound imaging data were adjusted for baseline diameter. RESULTS: The healthy comparison group had a significantly greater FMD response (9.5%±2.9%) than both the chemotherapy only (6.5%±2.6%) and chemotherapy combined with radiation (7.1%±2.6%) groups. No statistical differences were observed in nitrate-mediated EID between the healthy comparison group (27.0%±5.0%) and the chemotherapy only (24.7%±6.7%) or chemotherapy combined with radiation (25.2%±7.1%) groups. Among the ALL survivors, female subjects had a significantly greater FMD and nitrate-mediated EID than male subjects even after correcting for baseline brachial artery diameter. CONCLUSIONS: These data suggest that young adults treated for ALL during childhood are at risk for impaired FMD regardless of whether or not they received cranial irradiation. The extent to which this mechanism relates to early development of cardiovascular disease in long-term childhood ALL survivors remains to be determined. © 2008 Lippincott Williams & Wilkins, Inc.