The global multi-institutional registration trial (ELIANA) of CD19.41BB.zeta chimeric antigen receptor (CAR) T cell therapy forged the path to the first FDA-approved CAR T product, tisagenlecleucel. Since its approval, extensive post-market experience with CAR T cells in children and young adults has amassed, allowing several multi-institutional efforts to leverage real-world data. Real-world data has validated clinical trial findings and provided insights into CAR T-cell use in patient groups not included in early clinical trials, such as children <
3 years, patients with active CNS and isolated extramedullary disease, and patients treated in first relapse. Data from multi-centered consortia has also identified cohorts who experienced inferior outcomes post-tisagenlecleucel, informing high-risk groups for whom further treatment optimization is needed, and delineating treatment variables, such as CAR T cell dose and lymphodepleting chemotherapy pharmacokinetics, that impact outcomes. In this early stage of CAR T-cell therapies, real-world experience provides an increasingly rich data reservoir and an invaluable resource to investigate and address clinical gaps for CAR T recipients. This review highlights key insights gained from post-market studies that have informed clinical use of CAR T-cell therapy for children and young adults with B-ALL.