Chemotherapy-associated toxicities and poor outcomes are common in patients with Down syndrome-related acute lymphoblastic leukemia (DS-ALL). The researchers calculated tisagenlecleucel in 16 patients with DS-ALL in two phase 2 trials (ELIANA [NCT02435849], ENSIGN [NCT02228096]) and a phase 3b, managed access protocol (B2001X [NCT03123939]). Patients were 5 to 22 years old, with a median of two prior lines of therapy (range, 1 to 4) and four (25%) had previously received stem cell transplants. Complete response (CR) or complete remission with incomplete blood count recovery (CRi) was observed in 14 of 16 patients (88%);the outcome was extremely favorable: of 14 patients with CR/CRi, only 2 (14%) had minimal residual disease-negative. CD19-negative relapses occurred in six patients (43%) during median follow-up of 13.2 months (range, 0.5–49.3) (3 CD19-negative; 3 unknown). Furthermore, 9 patients had ongoing remissions ranging from 6 to 48 months in duration. About 16 and 14 patients experienced any-grade or grade 3/4 AEs, respectively. The incidence of grade 3/4 cytokine release syndrome was 44% among those who experienced any-grade AEs, whereas neurological events occurred in 13% of these people. Furthermore, 44% of patients in the research had a grade 3/4 prolongation of their cytopenias. There were no grade 3/4 infections identified.The long-term persistence of Tisagenlecleucel, as well as the expansion in population size and incidence, were comparable to those previously reported. In children/young adults with DS-ALL, tisagenlecleucel was comparable to ALL patients without DS in terms of remission rates, tolerable adverse effects, and long-term success.