{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:40:36Z","timestamp":1777293636084,"version":"3.51.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Blinatumomab, a bispecific T-cell engager targeting CD3+ and CD19+, promotes T cell\u2013mediated cytotoxicity against B-cell precursor acute lymphoblastic leukemia (B-ALL). While its efficacy is established in relapsed\/refractory (R\/R) disease, its role as preemptive therapy for minimal residual disease (MRD)\u2013positive patients or those experiencing chemotherapy delays remains undefined. Predictors of treatment failure also require further investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this multicenter retrospective study, 105 patients who received blinatumomab were enrolled. Of these, 30 had R\/R ALL, 21 were in complete remission (CR) with MRD positivity (CR-MRD<jats:sup>pos<\/jats:sup>), and 54 experienced chemotherapy delays. Eight patients received blinatumomab directly as reinduction therapy and 22 patients received burden-reduction chemotherapy prior to blinatumomab.  In total, 11 children were in R\/R status and 40 were in CR-MRD<jats:sup>pos<\/jats:sup> before treatment. Patients were subsequently bridged to stem cell transplantation, chimeric antigen receptor T-cell therapy (CAR-T), or protocol continuation. Treatment response was analyzed across CR-MRD<jats:sup>pos<\/jats:sup>, R\/R, and CR with MRD negativity (CR-MRD<jats:sup>neg<\/jats:sup>). Immune reconstitution profiles (T-cell subsets, cytokine dynamics), cytogenetic markers, and clinical outcomes were assessed to identify predictors of treatment resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CR rate was 81.8% in R\/R and 82.5% in CR-MRD<jats:sup>pos<\/jats:sup> patients (P = 1.000). Of 74 courses with CR-MRD<jats:sup>neg<\/jats:sup>, 73 remained MRD-negative during treatment. Univariate analysis revealed poor cytogenetics (P = 0.0001), CD19+ B-cell loss (P = 0.046), and BCR-ABL1 positivity (P = 0.002) as predictors of poor response. Cox regression analysis identified high MRD (P = 0.014), BCR\/ABL1 (P = 0.065), and poor cytogenetics (P = 0.025) as independent risk factors. Blinatumomab significantly increased CD3+ T cells [0.96 (0.03\u20133.79) to 1.13 (0.26\u20137.74) \u00d710<jats:sup>9<\/jats:sup>\/L, P = 0.016], along with CD4+ [0.35 (0.01\u20131.39) to 0.47 (0.07\u20132.94) \u00d710<jats:sup>9<\/jats:sup>\/L] and CD8+ T cells [0.41 (0.01\u20132.39) to 0.56 (0.07\u20136.07) \u00d710<jats:sup>9<\/jats:sup>\/L] (P = 0.005 and P = 0.006, respectively).The 1-year event-free survival for CR-MRD<jats:sup>neg<\/jats:sup>, CR-MRD<jats:sup>pos<\/jats:sup>, and R\/R patients was 97.8% \u00b1 2.2%, 86.7% \u00b1 6.2%, and 73.3% \u00b1 8.1%, respectively (P = 0.001), while overall survival was 97.8% \u00b1 2.2%, 100%, and 93.3% \u00b1 4.6% (P = 0.029).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Blinatumomab effectively clears MRD as preemptive therapy and serves as a bridging strategy during chemotherapy delays in pediatric B-ALL, while maintaining high response rates in R\/R cases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1607138","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T05:31:56Z","timestamp":1758173516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Blinatumomab demonstrates MRD eradication in MRD-positive\/chemotherapy-delayed pediatric B-ALL and high response in relapsed\/refractory cases: a multicenter cohort 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