Prognostic Impact of TP53 Mutations in Newly Diagnosed Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single-Center Study from China

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric 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 initial diagnosis, they are enriched at relapse and have been implicated as adverse prognostic markers. However, their clinical significance in newly diagnosed pediatric B-ALL, particularly in Chinese cohorts, remains insufficiently defined. Methods: We retrospectively analyzed 460 children with newly diagnosed B-ALL enrolled in the CCCG-ALL2015 extended protocol at the Children’s Hospital of Soochow University (October 2020–July 2024). Baseline characteristics, cytogenetics, molecular genetics, and treatment outcomes were compared between TP53 wild-type (TP53wt, n = 443) and mutant (TP53mut, n = 17) patients. Next-generation sequencing was used to identify mutations. Minimal residual disease (MRD) was assessed by flow cytometry. Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses, and exploratory analyses examined the impact of variant allele frequency (VAF) on relapse and survival. Results: The frequency of TP53 mutations was 3.7%, predominantly clustering in the DNA-binding domain, with hotspot variants at G245, R248, R249, R273, and R282. Compared with TP53wt, patients with TP53mut were more frequently ≥ 10 years old and classified into intermediate-risk group. Kaplan–Meier analysis showed comparable overall survival (OS) between TP53mut and TP53wt patients (3-year OS: 92.3% vs. 98.2%; P  = 0.14), but relapse-free survival (RFS) was significantly worse in the TP53mut group (3-year RFS: 49.5% vs. 89.6%; P  < 0.001). Notably, all relapse events occurred in patients with pathogenic TP53 variants. 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), alongside male sex, KMT2A rearrangements, and intermediate/high-risk classification. For OS, BCR::ABL1 was the only independent risk factor. Conclusions: Although rare at diagnosis, TP53 mutations in pediatric 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.