Background Blinatumomab has demonstrated its efficacy and safety in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). The objective of this analysis was to describe the responses and toxicities of blinatumomab in pediatric patients with different leukemic burdens in the bone marrow. Methods We enrolled patients aged 0-18 years who were diagnosed with CD19-positive B-ALL and treated with blinatumomab between January 2021 and May 2023 from 14 centers in China. Results A total of 307 patients were enrolled in this analysis. The complete remission (CR) rate was 72.1% among 61 patients with ≥5% blasts(non-complete remission, NCR group), of whom 90.9% achieved minimal residual disease (MRD) negativity. Among 93 patients with <5% blasts but multiparametric flow cytometry MRD (MFC-MRD) positive(MRD+ group), 96.8% achieved MRD negativity. Of the 153 MFC-MRD negative patients(MRD- group), 60.0% and 65.5% turned quantitative polymerase chain reaction MRD (qPCR-MRD) or next-generation sequencing MRD (NGS-MRD) negative, respectively. Additionally, Patients in the MRD+ and MRD- groups had significantly better outcomes than those in the NCR group, with 30-month OS rates of 91.6% (95% CI: 0.857-0.979), 95.3% (95% CI: 0.915-0.993), and 77.6% (95% CI: 0.674-0.894), respectively (P<0.001), and 30-month RFS rates of 90.7% (95% CI: 0.847-0.972), 93.3% (95% CI: 0.890-0.979), and 64.4% (95% CI: 0.495-0.837), respectively (P<0.001). There was no statistically significant difference in OS between the patients who achieved MFC-MRD negativity in the NCR group and those in the MRD+ group, with 30-month OS rates of 85.7% (95% CI: 0.745-0.987) and 93.2% (95% CI: 0.881-0.986), respectively (P=0.270). In this study, 41% of patients experienced grade ≥3 adverse events (AEs), with hematological toxicity being the most common (32.9%). The severe adverse events, such as cytokine release syndrome (CRS) and neurotoxicity, occurred at a low rate, particularly grade ≥3, at 3.6% and 2.6%, respectively. Conclusion Overall, these results indicate that blinatumomab is effective and well-tolerated. Patients with a lower leukemia burden before blinatumomab administration tend to have better overall survival and relapse-free survival with fewer AEs.