Context: Survivors of childhood acute lymphoblastic leukemia (ALL) become obese and are at increased risk of morbidity and mortality post-therapy.

Objective: We determined the association of cranial radiotherapy (CRT) and/or sex with levels of total, regional, and ectopic fat storage, metabolic risk, insulin-like growth factor-1 (IGF-1) and leptin in adult ALL survivors.

Design, Setting, Patients: A cross-sectional analysis of 52 male (15 CRT treated) and 62 female (24 CRT treated) young adult ALL survivors was conducted.

Main Outcomes: We assessed levels of visceral fat, subcutaneous abdominal and thigh fat, liver and muscle fat using computed tomography; total fat and lean body mass using dual energy x-ray absorptiometry; and IGF-1 and leptin levels by radioimmunoassay.

Results: Controlled for age and race, ALL survivors treated with CRT had higher levels of abdominal and visceral fat, body fat percentage, metabolic risk (insulin resistance and dyslipidemia) and leptin, but lower lean mass and IGF-1 levels than non-CRT survivors (P 0.05 for each). Levels of IGF-1 were inversely associated with total, abdominal and visceral fat in both sexes (P < 0.05 for each). Female ALL survivors had less lean mass and visceral fat but higher total and subcutaneous abdominal fat than males (P < 0.05 for each). Neither sex nor CRT was associated with muscle and/or liver fat content (P > 0.1).

Conclusion: Among young adult ALL survivors, CRT is a risk factor for elevated total, abdominal and visceral adiposity, a reduced fat-free mass, elevated metabolic risk, and altered IGF-1 and leptin levels.