Prognosis of Acute Myeloid Leukemia Based on TP53 Mutation Among Adult Patients: A Systematic Review and Meta-Analysis.

Background & Objective: Acute Myeloid Leukemia (AML) is a biologically diverse malignancy influenced by genetic abnormalities, with TP53 mutations playing a key role. Found in 5-10% of de novo AML and more common in therapy-related and secondary AML, TP53 mutations correlate with poor prognosis, chemoresistance, and reduced survival due to defective apoptosis and increased leukemic proliferation. These mutations often coexist with complex karyotypes and are more frequent in older patients, highlighting the need for improved prognostic tools and targeted therapies. This systematic review assessed the prognostic impact of TP53 mutations on overall survival (OS) and relapse-free survival (RFS) in adult AML. Methods: Following PRISMA guidelines, PubMed, Scopus, and Web of Science were searched through January 2025 for studies reporting OS and/or RFS by TP53 mutation status in adult AML. Data on study design, patient demographics, mutation frequency, and outcomes were extracted. Pooled hazard ratios (HRs) for OS and RFS were calculated using a random-effects model. Results: A total of 65 studies comprising over 6,000 adult AML patients were included in this systematic review and meta-analysis. The pooled HR for OS in TP53-mutated patients was 2.22 (95% CI: 2.08-2.37), indicating significantly worse survival than wild-type patients. For RFS, the pooled HR was 2.25 (95% CI: 1.98-2.56), reflecting a higher relapse risk. Heterogeneity was moderate for OS (I²=71%, p<0.01) and low for RFS (I²=0%, p=0.58). Conclusion: TP53 mutations strongly predict poorer overall and relapse-free survival in adult AML, supporting their integration into clinical risk models and emphasizing the need for novel therapeutic approaches in this high-risk subgroup.