Clinical evidence and biological mechanisms linking obesity to adverse outcomes in pediatric and adolescent acute lymphoblastic leukemia

This review critically evaluated the relationship between obesity and survival outcomes in Acute Lymphoblastic Leukemia (ALL), highlighting key evidence gaps and exploring the biological mechanisms that may contribute to this association. In patients with ALL, obesity is consistently associated with a higher incidence of severe treatment-related toxicities, increased frequency of therapy delays, and reduced event-free survival. This connection is most pronounced in pediatric and adolescent ALL populations, whereas evidence supporting a similar effect in adults remains limited. Proposed biological mechanisms underlying these adverse outcomes include increased bone marrow adiposity, chronic low-grade inflammation, dysregulated insulin signaling and obesity-associated alterations in the gut microbiome. The current body of evidence identifies obesity as a clinically significant risk factor that defines a vulnerable subgroup of ALL patients, supporting the need for enhanced toxicity surveillance, individualized treatment strategies, and optimized supportive care interventions. Elucidation of the biological pathways linking obesity to adverse ALL outcomes may also inform the development of novel therapeutic approaches aimed at mitigating obesity-driven morbidity and mortality in this high-risk population.