<![CDATA[Acute lymphoblastic leukemia (ALL) non-Philadelphia chromosome–positive (non-Ph+) is a major subtype of leukemia with high relapse rates and significant toxicity from conventional chemotherapy. This study evaluated the efficacy and safety of targeted therapy versus chemotherapy in non-Ph+ ALL. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Five databases were searched for randomized controlled trials (RCTs) comparing both interventions, with outcomes including overall survival (OS), event-free survival (EFS), disease-free survival (DFS), minimal residual disease (MRD), and grade ≥3 adverse events (AEs). Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool, and pooled estimates were calculated using hazard ratios (HRs) and risk ratios (RRs). Six RCTs from 7,154 records were included. Targeted therapy significantly improved OS (HR 0.59; 95% CI 0.42–0.84) and DFS (HR 0.73; 95% CI 0.55–0.96), with a non-significant trend in EFS (RR 0.69; 95% CI 0.48–1.01). MRD negativity increased after sensitivity analysis (RR 1.85; 95% CI 1.44–2.37), while severe adverse events were reduced (RR 0.88; 95% CI 0.80–0.97). Overall, targeted therapy is associated with improved survival with an acceptable safety profile in non-Ph+ ALL]]>
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