BACKGROUND: New highly effective, but expensive, immunotherapies have revolutionized the treatment of relapsed pediatric acute lymphoblastic leukemia (ALL) but their long-term clinical and economic impact is unclear. We developed the ALL Policy microsimulation model to estimate long-term clinical and economic outcomes for patients with pediatric ALL aged 0-17 in Ontario, Canada. We also illustrate the model's clinical utility through a cost-effectiveness analysis of blinatumomab in relapsed B-cell ALL. METHODS: The ALL Policy model is informed using health administrative data and chart abstracted data from Ontario, Canada, and published literature. The model estimates lifetime risk of relapse, bone marrow transplant (BMT), conditional life expectancy, quality-adjusted life years (QALY), and total healthcare costs for individuals with pediatric ALL, and can be stratified by relevant clinical characteristics (eg, B-cell or T-cell lineage). Additionally, we subset the model to patients with relapsed B-cell ALL to illustrate use of the model in estimating the cost-effectiveness of blinatumomab vs standard chemotherapy. RESULTS: Simulated pediatric ALL patients diagnosed from 2002-2012 had a projected conditional life expectancy of 64.90 years. The lifetime risk of BMT was estimated at 12.5%. Lifetime healthcare costs were 44,433 CAD (95% CI 13,314, 03,430). Treatment with blinatumomab compared to standard chemotherapy post-relapse was estimated to result in 1.08 additional QALYs and an additional cost of 9,410 CAD (incremental cost-effectiveness ratio of 4,885/QALY). CONCLUSION: The ALL policy model can serve as a modeling foundation for timely economic evaluation. Introduction of blinatumomab in relapsed B-cell ALL may be a cost-effective strategy.