Loss-of-function inherited TP53 genetic variants appear to predispose children to acute lymphoblastic leukemia (ALL) and to adverse outcomes with ALL therapy, according to a recent study. Investigators analyzed the TP53 variants’ link with ALL and treatment outcomes in >3,800 participants from 2 Children’s Oncology Group frontline ALL clinical trials. They also looked at the gene’s prevalence in non-ALL controls. Among the results:

• 49 unique nonsilent rare TP53 coding variants were identified in 77 patients sequenced.
• 22 variants were classified as pathogenic.
• Patients with ALL were >5 times more likely than controls to carry TP53 pathogenic variants.
• Children with TP53 pathogenic variants were aged an average of 15.5 years at ALL diagnosis, vs 7.3 years in those without the variants.
• They were also more likely to have hypodiploid ALL (65% v 1%, respectively).
• Carriers were ~4 times more likely to experience inferior event-free and overall survival.
• One-fourth of carriers experienced second cancers, vs <1% of noncarriers.