Prognostic significance of TP53 mutations and VAF in ND ALL

Results from a retrospective analysis investigating the prognostic significance of TP53 mutations and their variant allele frequency (VAF) in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) (N = 652) were published in Blood by Azevedo et al.

Key data: TP53 mutations occurred in 17.2% of patients overall. The median age of patients with TP53 mutations was 61 years vs 45 years in patients with wild-type (WT) TP53 (p < 0.001). The median TP53 VAF was 42% (range, 1−94%) and was highest in patients with low-hypodiploid/near-triploid karyotype. In patients aged ≥60 years with Philadelphia chromosome-negative (Ph−) B-cell ALL (B-ALL), 4-year event-free survival (EFS) was 28% for patients with TP53 VAF ≥45% (hazard ratio [HR], 2.24; p = 0.02) vs 57% for patients with TP53 VAF <45% (HR, 0.85; p = 0.67). Four-year overall survival (OS) was 28% for patients with TP53 VAF ≥45% (HR, 2.61; p = 0.009) vs 58.7% for patients with TP53 VAF <45% (HR, 1.04; p = 0.93). Among patients aged <60 years with TP53 mutations, 4-year EFS and OS rates were comparable with those for patients with WT TP53, at 57% and 62%, respectively. 

Key learning: In this study, TP53 VAF ≥45% was identified as a potential prognostic marker for poor outcomes in patients aged ≥60 years with Ph− B-ALL. High VAF may increase the risk of relapse but is not independently associated with reduced survival in younger patients.