Beyond survival: late effects, inflammaging and potential role of flavonoids in long term care of childhood acute lymphoblastic leukemia survivors

Abstract Survival outcomes for childhood acute lymphoblastic leukaemia (cALL) in Malaysia have improved markedly, with survival rates of >90 % in the best-risk groups reported recently. However, long-term survivorship remains challenged by a high burden of late effects, with many survivors developing severe – and in some cases life-threatening – health complications within two decades of diagnosis. This narrative review discusses the potential main driver of these comorbidities, which is chronic inflammation or ‘inflammaging,’ as well as the potential deregulation of the CD38-NAD-Sirtuins axis, as a consequence of treatment-related insults. Thus, there is an urgent need for effective, evidence-based interventions to mitigate chronic health conditions in this growing population of young adult survivors of childhood cancer. We examine the potential role of dietary flavonoids, which are bioactive compounds abundant in fruits, vegetables, and common daily foods, in reducing long-term treatment-related complications due to their established anti-inflammatory and antioxidant properties. Specifically, we focus on five flavonoids of interest, namely apigenin, quercetin, fisetin, epigallocatechin gallate, and luteolin, and summarise current evidence regarding their mechanistic actions and potential utility as adjunctive strategies to alleviate late effects in childhood cancer survivors.