Chemotherapy-induced oxidative injury in pediatric acute lymphoblastic leukemia: The role of N-acetylcysteine (Review).
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Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. However, intensive chemotherapy frequently leads to notable organ toxicity, much of which is mediated by treatment-induced oxidative stress. Reactive oxygen species (ROS) generated during cytotoxic therapy contribute to tissue damage, including the liver, heart and nervous system. Current adjunctive therapies provide drug-specific protection, such as dexrazoxane for anthracycline-induced cardiotoxicity, but they do not address the shared ROS-generating pathway, a common mechanism of chemotherapy-induced toxicity across multiple agents and tissues. The present narrative review synthesizes the biochemical rationale, preclinical evidence and translational considerations for N-acetylcysteine (NAC) as a redox-modulating adjunct therapy in pediatric ALL. NAC acts as a glutathione precursor, scavenges reactive oxygen and nitrogen species, chelates redox-active metals, and modulates inflammatory signaling pathways. These properties have been associated with cytoprotective effects in preclinical models of chemotherapy-induced cardiotoxicity, hepatotoxicity, neurotoxicity and oxidative injury. Available evidence suggests that NAC can reduce treatment-related toxicity without consistently compromising antitumor efficacy, although outcomes appear to be dependent on timing, dosage and treatment context. While the favorable safety, low cost and accessibility of NAC support its potential clinical utility, current evidence remains limited, particularly in pediatric ALL populations. In conclusion, NAC represents a promising but context-dependent adjunctive strategy for mitigating chemotherapy-induced toxicity in pediatric ALL. Further well-designed clinical studies are required to define its optimal use, including timing, dosing and impact on oncological outcomes.