Introduction: B-cell acute lymphoblastic leukemia (B-ALL) has a very high relapse rate, with dismal median overall survival (mOS) and 5-year survival rates afterwards. Recently, numerous trials involving chimeric antigen receptor (CAR) T-cell therapy have demonstrated promising outcomes in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). We aim to explore and analyze the outcomes of available studies involving CAR-T cell therapy and B-ALL.

Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Cochrane, Embase, Google Scholar, and ClinicalTrials.gov (inception to May 2025) was conducted using MeSH terms for “Acute Lymphoblastic Leukemia” and “CAR-T cell therapy.” After screening and excluding review articles, meta-analyses, and studies without a patient population of interest, eight studies reporting the outcomes of CAR-T cell therapy in R/R ALL were selected for inclusion from a total of 537 references. For outcomes reported in two or more studies, a meta-analysis was conducted using a random-effects model. Results were expressed as prevalence estimates with 95% confidence intervals (CIs). Some characteristics were described systematically.

Results: A total of 450 patients with R/R B-ALL from four Phase I, two Phase II, and two Phase I/II trials were included in this study. The median age was 22 years (range, 1.3-81), with the majority (n = 170/323, 53%) being males, and 51% having had a prior stem-cell transplant (SCT) (n = 191/376). ECOG status was reported as 0 (n =65/170, 38%) and 1 (n = 105/170, 62%). CAR-T targets included CD19 antigens (n = 405, 90%), CD22 antigens (n = 18, 4%), and dual CD19/CD22 antigens (n = 27, 6%). The median follow-up time was 21.8 months (range, 1-65). The pooled rates for overall response (ORR), complete remission (CR), complete remission with incomplete hematological recovery were 78% (95% CI, 0.72-0.83, p = 0.24, I2= 29%), 66% (95% CI 0.62-0.70, p = 0.00, 12= 79%), and 20% (95% CI, 0.15-0.25, p = 0.74 I2=0%), respectively.The pooled rates for negative minimal residual disease (MRD) and event-free survival (EFS) were 83% (95% CI, 0.79-0.87, p = 0.00, I2= 86%) and 51% (95% CI 0.45-0.57, p = 0.64, I2= 0%), respectively.The pooled rates for OS at 12 months and 24 months were 69% (95% CI, 0.64-0.73, p = 0.03, 12= 60%) and 61% (95% CI 0.53-0.70, p = 0.05, 12= 75%), respectively. The pooled rates for grade 3 or higher toxicities and cytokine release syndrome (CRS) were 73% (95% CI, 0.67-0.78, p = 0.00, I2 = 95%) and 77% (95% CI, 0.73-0.81, p = 0.00, I2= 82%), respectively.

Conclusion: CAR-T cell therapy shows promising results in patients with R/R B-ALL, with encouraging OS at 1 and 2 years, indicating durable remission. Continued prospective trials with larger patient populations and longer follow-ups are required to consolidate these findings.

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2025
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