TP53 deletion as an MRD‐dependent risk factor in childhood B‐ALL: A post hoc analysis from a prospective cohort

Abstract The effect of TP53 alterations on childhood B‐cell acute lymphoblastic leukemia (B‐ALL) remains unclear. To investigate the prognostic value of TP53 deletion ( TP53 del ) and TP53 mutation ( TP53 mut ), this post hoc study used fluorescence in situ hybridization test to detect TP53 del in 907 newly diagnosed B‐ALL patients from a prospective cohort of Chinese Children's Cancer Group ALL‐2015 trial. Targeted gene sequencing was used to identify TP53 mut in 342 out of the 907 patients. TP53 del was detected in 4.4% of patients. The frequency of hypodiploidy was higher in TP53 del subgroup (7.5% vs. 0.5%, p = 0.002), but patients with TP53 del were less likely to have other recurrent genetic abnormalities, including BCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and KMT2A rearrangements. Univariable and multivariable analyses indicated that TP53 del was an independent risk factor for overall survival (OS) and disease‐free survival (DFS). Furthermore, stratification analysis revealed that TP53 del was associated with lower 5‐year DFS in patients with positive minimal residual disease (MRD) after induction in the intermediate‐risk group (0.0% vs. 58.0% [95% confidence interval [CI] 49.2%–68.3%], p < 0.001), suggesting an MRD‐dependent pattern. However, somatic TP53 mut was not associated with poor survival (81.8% [95% CI 61.9%–100.0%] vs. 84.9% [95% CI 81.1%‐89.0%], p = 0.971). In summary, TP53 del may serve as a predictor for poor prognosis in pediatric B‐ALL. In particular, children in the intermediate‐risk group with positive MRD and TP53 del may require more aggressive treatment.