B-cell Acute Lymphoblastic Leukemia (B-ALL) has a 90% overall survival (OS) rate in children and young adults. However, in the relapsed/refractory (R/R) setting, 5-year OS drops to 50% after the first relapse, falling to 20–30% in R/R B-ALL post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). Given this scenario, the ELIANA trial evaluated the CD19-targeting CAR T-cell therapy Tisagenlecleucel (Tisa-Cel) in R/R B-ALL, reporting complete response (CR) rates of 81%. A 3-year follow-up showed event-free survival and OS rates of 44% and 63%, respectively. Among grade 3 or 4 adverse events, Cytokine Release Syndrome (CRS) occurred in 48% of cases and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) in 13%, though real-world studies report lower rates of 16% for CRS and 9% for ICANS. Another less frequent, but more serious, adverse event is Macrophage Activation Syndrome (MAS). Tisa-Cel was approved in Brazil in 2022 for R/R B-ALL patients up to 25 years of age, including post-allo-HSCT. Therefore, this study aims to retrospectively report the cases of patients with R/R B-ALL treated with Tisa-Cel at our institution between 2022 and 2024, based on the analysis of medical records.

We report a series of three R/R B-ALL cases, aged 15 to 24, all heavily pre-treated with a median of 3 therapy lines; two had relapsed post-allo-HSCT. Following leukapheresis, all patients received Fludarabine and Cyclophosphamide lymphodepletion and a Tisa-Cel infusion. With a median follow-up of 10 months (10-13), two of the three patients remain alive and in CR without cytopenias. Patient 1: A 15-year-old male with Philadelphia (Ph)-like B-ALL, refractory to two lines (including use of Blinatumomab), and relapse in central nervous system post-allo-HSCT, received CAR-T therapy while in CR. He had no CRS or ICANS and remains with no evidence of disease. Patient 2: A 23-year-old male with lymphoblastic lymphoma Ph negative localized in the tibia (no medullary involvement), refractory to two lines and not yet submitted to allo-HSCT, received CAR-T in a partial response (PR). He developed grade 1 CRS without ICANS and achieved PR at D30, and CR at D60. Patient 3: A 24-year-old female with Ph positive B-ALL, refractory after more than 3 lines of therapy lines and relapsed post-allo-HSCT, received CAR-T with active disease (7.6% blasts in bone marrow). She developed grade 3 CRS and grade 1 ICANS, managed with IL-1 and IL-6 inhibitors, intensive care and dexamethasone. She achieved CR at D+30 but died at D+55 from complications, including severe fungal infection, occlusive-venous-disease and MAS.

Despite the small cohort, this real-world data contributes to a better understanding of treatment responses and adverse effects. The reported outcomes were similar to those found in the literature, particularly in real-world studies. Therefore, anti-CD19 CAR-T appears to be a potentially curative option in R/R B-cell ALL, even in cases of relapse after allo-HSCT, with the advantage of not requiring an RC prior to its administration.