儿童急性髓系白血病幸存者化疗相关认知障碍的探讨

Chemotherapy-related cognitive impairment (CRCI) has mainly been explored within the context of childhood ALL survivors, whereas data analyzing for pediatric AML neurocognitive outcomes following chemotherapy remains sparse. Standard induction therapy for pediatric AML involves the use of high dose Ara-C intrathecal chemotherapy for CNS prophylaxis, sometimes combined with Methotrexate, both well-documented causal agents regarding neurotoxicity and their link to CRCI. In order to better understand how standard induction therapy affects neurocognitive outcomes for childhood survivors of AML, we searched PubMed, EMBASE, and PsycINFO (2015-2025) using terms such as “childhood acute myeloid leukemia”, “neurocognitive outcomes”, “ ‘chemo brain' ”, and “cognitive”. Inclusion criteria were limited to pediatric AML-specific cohorts who had undergone validated neuropsychological testing and/or self-reported outcomes. Exclusion criteria were HSCT/cranial RT unless chemotherapy-only results were separable. Three peer-reviewed studies, and one meeting abstract were found which met the criteria. Across AML-specific cohorts, treatment with conventional therapy was associated with impairment in at least one neurocognitive domain, with the relative risk for impairment in two domains being demonstrably higher in the CCSS AML cohort. These studies revealed broad impairment across all domains, with working memory emerging as being notably affected, and exhibiting lasting negative effects on QoL persisting well into adulthood amongst these cohorts. Other similarly impaired neurocognitive domains corresponded to issues with emotional regulation and efficiency accomplishing tasks. One study found no difference in FSIQ when comparing AML survivors to population means, yet their study had an n=12, and showed time since diagnosis, and age at assessment were significant predictors of FSIQ. Additionally, these studies also support the risk for CRCI independent of HSCT, as large survivorship analysis differentiating intense chemotherapy with or without HSCT still found measurable neurocognitive impairment regardless of treatment modality. Given the current evidence, childhood survivors of AML exposed to standard induction therapies are at risk of developing CRCI, with working memory and executive functioning being likely impaired. A significant fraction of pediatric AML survivors experience CRCI may be suffering from unrecognized health conditions, and as such may largely benefit from increased neurocognitive monitoring and resources. As for future pediatric AML patients, careful consideration of these neurocognitive consequences could inform risk-stratified intensity adjustments and introduce targeted neuroprotective strategies during therapy, minimizing cognitive morbidity and allowing patients to not only live longer, but live better.