Background: The Evolving Landscape of CAR T-Cell Therapy in Pediatric B-ALL
Chimeric antigen receptor T-cell (CAR-T) therapy has fundamentally transformed the therapeutic landscape for pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among the commercially available CD19-directed CAR-T products, tisagenlecleucel has demonstrated remarkable efficacy, with long-term remission rates approaching 60% in previously treated populations. Despite these advances, disease relapse remains the predominant cause of treatment failure, underscoring the urgent need to identify reliable prognostic biomarkers that can stratify patients and guide risk-adapted therapeutic strategies.
While several clinical and biological factors have been associated with inferior outcomes following CAR-T therapy—including high disease burden, prior hematopoietic stem cell transplantation (HSCT), and specific cytogenetic abnormalities—the prognostic significance of tumor suppressor gene alterations, particularly TP53 mutations and deletions, remains incompletely characterized. TP53, encoding the guardian of the genome p53 protein, plays a pivotal role in cellular stress responses, DNA repair, and apoptosis. Germline TP53 mutations are associated with Li-Fraumeni syndrome, a hereditary cancer predisposition condition with markedly elevated leukemia risk. However, the impact of somatic TP53 alterations on CAR-T therapy outcomes in pediatric B-ALL has not been systematically evaluated until recently.
