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The purpose of this pharmacoeconomic analysis was to compare pegaspargase, a newer chemotherapeutic agent used for treating acute lymphoblastic leukemia, with native Escherichia coli l-asparaginase in induction, delayed intensification 1 and delayed intensification 2.A subset of patients with newly diagnosed, standard-risk, acute lymphoblastic leukemia enrolled in the Children's Cancer Group (CCG) study CCG-1962 at seven participating institutions gave consent and was enrolled in our pharmacoeconomic analysis study. Societal (transportation, lodging, missed workdays, food, babysitter) and payer (frequency of encounters) cost data were collected from diaries (n = 27). Additional payer costs, such as drug costs, cost per clinic visit, and cost per inpatient day stay were collected from patients in CCG-1962 and participating institutions. We considered costs of therapy, including higher pegaspargase costs when comparing regimens of pegaspargase versus native E. coli l-asparaginase in induction, delayed intensification 1, and delayed intensification 2.Our results showed that the costs of the two therapies were similar from the payer perspective, with pegaspargase costing 1.8% more than E. coli l-asparaginase. The difference between groups also was small (<1%) from the societal perspective. Inpatient stay accounted for 88% of pegaspargase payer costs and 91% of the native E. coli l-asparaginase costs.We recommend that pegaspargase not be withheld from treatment protocols solely because of its higher pharmacy costs.