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.