Prognostic impact of TP53 mutations in newly diagnosed paediatric B-cell acute lymphoblastic leukaemia: a single-centre study from China

Background Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy with cure rates exceeding 90% under modern treatment protocols. Nevertheless, 10–20% of patients relapse, and post-relapse survival remains poor. Although TP53 mutations are rare at the initial diagnosis, they are enriched at relapse and have been implicated as adverse prognostic markers. However, their clinical significance in newly diagnosed paediatric B-cell acute lymphoblastic leukaemia (B-ALL), particularly in Chinese cohorts, remains unclear. Methods We retrospectively analysed 460 children newly diagnosed with B-ALL enrolled in the Chinese Children’s Cancer Group ALL-2015 extended protocol at the Children’s Hospital of Soochow University (October 2020 to July 2024). Baseline characteristics, cytogenetics, molecular genetics, and treatment outcomes were compared between TP53 wild-type (n = 443) and TP53-mutated (n = 17) patients. Next-generation sequencing was performed to identify mutations. Minimal residual disease (MRD) was assessed using flow cytometry. Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses, and exploratory analyses were used to examine the impact of variant allele frequency (VAF) on relapse and survival. Results TP53 mutations were detected in 3.7% of patients and mainly clustered in the DNA-binding domain. Compared with TP53 wild-type patients, TP53-mutated patients were more frequently aged ≥ 10 years and classified as intermediate risk. OS was comparable between groups (3-year OS 92.3% vs. 98.2%; P = 0.14), whereas RFS was significantly worse in the TP53-mutated group (3-year RFS 49.5% vs. 89.6%; P < 0.001). All relapses occurred in patients with pathogenic variants. In the treatment-evaluable cohort (n = 16), higher VAF was associated with inferior RFS (3-year RFS 0% vs. 64.0% ± 17.5%; P < 0.001). Multivariate Cox analysis confirmed TP53 mutation as an independent adverse prognostic factor for RFS (HR 3.26, 95% CI 1.03–10.34; P = 0.045). Conclusions Although rare at diagnosis, TP53 mutations in paediatric B-ALL are strongly associated with relapse and inferior RFS, underscoring their potential role as high-risk biomarkers. Incorporating TP53 status into risk stratification and exploring targeted or intensified therapeutic strategies may help improve outcomes in this high-risk subset.