Obesity effects on cyclophosphamide-induced DNA damage in hematopoietic cell transplant recipients

Cyclophosphamide, an alkylating agent, is metabolically activated to phosphoramide mustard, to form toxic DNA-DNA (G-NOR-G) crosslinks. Increased exposure to cyclophosphamide metabolites has been associated with treatment-related toxicity. The effect of obesity on exposure to cyclophosphamide-induced G-NOR-G crosslinks is not known. Therefore we sought to determine whether obesity affects the formation of cyclophosphamide-specific G-NOR-G crosslinks. Plasma cyclophosphamide concentrations and blood cell G-NOR-G amounts were measured. Overweight/obese patients received a significantly higher daily cyclophosphamide dose (median 3000 vs. 4450 mg, p