Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and although survival rates in children are high, adult B-lineage ALL (B-ALL) presents with high rates of relapse and refractoriness.[1,2] Chimeric antigen receptor (CAR)-T cell therapy, a form of personalized immunotherapy, has emerged as a revolutionary strategy for hematological cancers, showing transformative results where conventional treatments have failed.[3] This therapy involves genetically modifying a patient's T-cells to recognize and eliminate cancer cells.[3] Given its potential, this study aims to synthesize the current evidence on the efficacy and safety of CAR-T therapy in patients with relapsed or refractory (R/R) B-ALL.

To evaluate and synthesize the results on the efficacy and safety of different CAR-T treatments in patients with refractory B-ALL through a systematic review and meta-analysis of published clinical trials.

A systematic review and meta-analysis were conducted following PRISMA guidelines. A search of PubMed, SciELO, BVS, Cochrane Library, and Web of Science databases was performed for clinical trials published between 2014 and 2025 that evaluated CAR-T therapy for R/R B-ALL. A total of 27 single-arm, non-randomized clinical trials were included. Data on measurable residual disease negativity, cytokine-release syndrome and neurotoxicity were extracted. A meta-analysis of proportions was performed using a random-effects model to calculate pooled estimates and 95% confidence intervals.

The pooled analysis showed an overall MRD-negativity rate of 78.89% (95% CI: 73.17%–84.16%). Subgroup analysis showed rates of 79.70% for anti-CD19 constructs, 83.17% for dual anti-CD19/CD22, and 56.45% for anti-CD22 alone. The incidence of CRS of any grade was 80.91% (95% CI: 74.38%–86.79%), while severe CRS (Grade ≥ 3) occurred in 14.62% (95% CI: 9.35%–20.66%) of patients. Neurotoxicity of any grade was observed in 22.66% (95% CI: 14.17%–32.27%) of patients. Heterogeneity was observed across the analyses (I² from 66%–87%). CAR-T cell therapy induces high rates of complete remission and MRD negativity in adult patients with R/R B-ALL, representing a major advance for this historically poor-prognosis population. However, adverse events such as CRS and neurotoxicity are frequent. The significant heterogeneity among studies highlights the influence of factors like patient characteristics, CAR-T construct, and treatment protocols on outcomes. Future research should focus on optimizing CAR-T cell persistence, overcoming resistance, and refining patient selection to maximize the curative potential of this therapy.