OBJECTIVES: Treatment for Acute Lymphoblastic Leukemia (ALL) is complex, involving administration of multiple chemotherapeutic agents across multiple treatment phases. Native E. coli asparaginase, a bacterial-derived enzyme that depletes circulating asparagine on which leukaemic cells depend, is recognised as one of the most valuable drugs in the multi-agent treatment of ALL. This study aimed to compare treatment costs between native E. coli asparaginase and pegaspargase, a pegylated version of the native E. coli asparaginase presenting similar efficacy but longer half-life and less immunogenicity. METHODS: A cost-minimization analysis (CMA) was performed using a decision tree model based upon CAALL-F01, the most recent French protocol for the treatment of ALL in children and adolescents. Risk groups, dosing and administration schedule were derived from CAALL-F01 and only direct drug acquisition costs of the different forms of asparaginases were considered. In case of hypersensitivity reactions (reported in 30% and 2% of patients treated with native E. coli asparaginase and pegaspargase respectively), patients were switched to the second-line Erwinia-derived asparaginase. Other costs, such as day-care hospital admissions, laboratory tests, charges for premedication, and indirect costs were not included. RESULTS: The estimated cost for a patient initiating a treatment sequence with native E. coli asparaginase was €9,940 versus €4,670 with pegaspargase. This difference in cost is mainly due to the lower incidence of immunogenic reactions observed with the use pegaspargase avoiding broad usage of the costly second line Erwinia-derived asparaginase. For France, with an average of 471 children and adolescent diagnosed with de novo ALL per year, the total annual net cost was estimated at €4,681,798 and €2,199,580 for patients treated with native E. coli asparaginase and pegaspargase, respectively. CONCLUSIONS: In France, the use of pegaspargase instead of native E. coli asparaginase for the treatment of childhood ALL could be a cost-saving strategy.