Efficacy and Safety of Children With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia After Anti-CD19 CAR T-Cell Therapy Without Bridging Transplantation

This study aimed to explore the prognosis of patients with relapsed or refractory B -cell acute lymphoblastic leukemia (R/R B -ALL) after chimeric antigen receptor (CAR) T -cell therapies without bridging transplantation. The MRD status before CAR T -cell infusion was found to be associated with OS, EFS, and toxicity. Patients with MRD >= 1% constituted a distinct high -risk population that may benefit from additional interventions to optimize outcomes mediated by CAR therapy. Furthermore, patients who experienced CD19-negative relapse after infusion exhibited a less favorable OS outcome. Background: Anti-CD19 chimeric antigen receptor (CAR) T -cell therapies have demonstrated significant efficacy in achieving complete remission (CR) in pediatric patients with relapsed/refractory (R/R) B -cell acute lymphoblastic leukemia (B -ALL). However, a considerable number of patients experience relapse within 1 year after CAR T -cell therapy, leading to an extremely poor prognosis, particularly in patients without bridging transplantation. Materials and Methods: In our study, we investigated 42 children with R/R B -ALL who underwent anti-CD19 CAR T -cell therapy without bridging transplantation at our center. All patients were included in the response analysis and evaluated for survival and toxicity. Results: The cohort that received the CAR T -cell infusion exhibited a 100% CR rate by day 28 (d28). The overall survival (OS) at 4 years was 61.3% +/- 8.5%, and the event -free survival (EFS) was 55.9% +/- 7.9%, with a median followup duration of 50.1 months. Minimal residual disease (MRD) >= 1% was associated with inferior outcomes, resulting in lower 4 -year OS ( P = .033) and EFS ( P = .014) compared to MRD < 1%. The incidences of grade >3 cytokine release syndrome (CRS) and neurotoxicity were 26.8% and 23.8%, respectively. Furthermore, MRD >= 1% was identified as an independent factor associated with increased severity of CRS and occurrence of neurotoxicity. Conclusion: These findings suggest that reducing the pre -infusion MRD could serve as an effective treatment strategy to enhance the outcomes of CAR T -cell therapy.