University of Iowa Hospital & Clinics, Department of Psychiatry, Iowa City, IA, USA.
University of Alberta, School of Public Health, Edmonton, Alberta, Canada.
J Natl Cancer Inst. 2021 May 4;113(5):588-596. doi: 10.1093/jnci/djaa136.
The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only.
This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided.
Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92).
Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship.
本研究旨在探讨仅接受化疗治疗的急性淋巴细胞白血病（ALL）幸存者中，治疗与慢性健康状况与神经认知障碍之间的关联。
本横断面研究纳入了 1207 名 ALL 幸存者（54.0%为女性；平均年龄 30.6 岁）和 2273 名兄弟姐妹（56.9%为女性；平均年龄 47.6 岁），他们均完成了儿童癌症幸存者研究神经认知问卷。通过性别比较，多变量逻辑回归分析了幸存者和兄弟姐妹之间神经认知障碍的患病率。还研究了神经认知障碍与治疗暴露和慢性疾病（根据不良事件通用术语标准进行分级）之间的关系。统计检验为双侧。
与同性别兄弟姐妹相比，男性和女性 ALL 幸存者报告任务效率受损的患病率增加（男性：11.7%比 16.9%；调整后的优势比[OR]为 1.89，95%置信区间[CI]为 1.31 至 2.74；女性：12.5%比 17.6%；OR=1.50，95%CI=1.07 至 2.14），以及记忆受损（男性：11.6%比 19.9%，OR=1.89，95%CI=1.31 至 2.74；女性：14.78%比 25.4%，OR=1.96，95%CI=1.43 至 2.70）。在男性幸存者中，任务效率受损与 2-4 种神经疾病（OR=4.33，95%CI=1.76 至 10.68）和肺部疾病（OR=4.99，95%CI=1.51 至 16.50）有关，记忆受损与鞘内甲氨蝶呤累积剂量增加（OR=1.68，95%CI=1.16 至 2.46）和地塞米松暴露（OR=2.44，95%CI=1.19 至 5.01）有关。在女性幸存者中，2-4 级内分泌疾病与任务效率受损（OR=2.19，95%CI=1.20 至 3.97）和记忆受损（OR=2.26，95%CI=1.31 至 3.92）的风险增加有关。
神经认知障碍与甲氨蝶呤、地塞米松和慢性健康状况呈性别特异性相关，这突显了需要研究生理机制并通过生存研究监测其影响。
