Impact of TP53 mutation on survival outcomes in acute lymphoblastic leukemia at a tertiary center

Mutations in TP53 in acute lymphoblastic leukemia (ALL) predict poor outcomes, however, the literature in adults remains limited. In a retrospective study at Cleveland Clinic, we investigated the outcomes of 72 patients with next-generation sequencing (NGS) at baseline out of 161 patients from January 2017 to August 2023. Eleven patients had TP53 mutations (muTP53-ALL) (15.3%). Patients with muTP53-ALL were older (65 vs 56 years), had more high-risk cytogenetics (45% vs 16%), and no BCR-ABL1 rearrangements (34% vs 0) compared to wild-type TP53 (wtTP53). The muTP53-ALL group had lower flow-cytometry measurable residual disease (MRD)-negative responses (odds ratio: 0.1, 95%CI 0.01-0.47.8, p = .003) and worse 12-month overall survival (OS) compared to wtTP53 ALL (62% vs 90%, p = 0.023). The muTP53-ALL patients are less likely to achieve deep responses to first-line therapy and have worse long-term OS. Future studies should explore early transplants or the use of front-line immunotherapies to improve outcomes.