Effects of chemotherapy for acute lymphoblastic leukemia on cognitive function in animal models of contemporary protocols: A systematic literature review

Survival rates of childhood acute lymphoblastic leukemia (ALL) have improved greatly due to advanced therapies and supportive care. Intrathecal chemotherapy replaced cranial radiation due to radiation-induced neurotoxicity and late-effects. Survivors treated with chemotherapy-only experience neurologic and cognitive problems following cessation of treatment. Very long-term cognitive outcomes remain unclear. Animal models are being generated to assess late-effects of chemotherapy on cognitive function. Although, few address juvenile models of chemotherapy-induced cognitive impairment (CICI) and developing brain, results of this review outline neurocognitive effects of chemotherapy consistent with childhood ALL therapy. Studies demonstrate deficits across cognitive domains including spatial memory, executive function, short-term memory, anxiety and depression. Inflammation, oxidative stress, excitotoxity, and other metabolic disruptions may lead to neurodegeneration associated with cognitive impairment observed in ALL survivors. Interventions directly targeting these mechanisms may prevent and/or promote recovery of cognitive function and improve long-term outcomes. Evidence suggests success of anti-inflammatory and antioxidant treatments in reducing cognitive decline. Animal models provide basis for assessing effects of chemotherapy on neurologic processes to guide future clinical investigations.