Sands Stephen A, Harel Brian T, Savone Mirko, Kelly Kara, Vijayanathan Veena, Welch Jennifer Greene, Vrooman Lynda, Silverman Lewis B, Cole Peter D
Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, USA.
Division of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Avenue 7th Floor, New York, NY, 10022, USA.
Support Care Cancer. 2017 Feb;25(2):449-457. doi: 10.1007/s00520-016-3422-9. Epub 2016 Oct 10.
Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions.
This study collects CSF while prospectively assessing neurocognitive functioning (working memory, executive function, learning, processing speed, and attention) of ALL patients using the Cogstate computerized battery at six time points during and after the 2 years of leukemia treatment on a Dana-Farber Cancer Institute ALL Consortium trial.
Baseline data collected during the first 3 weeks of induction chemotherapy indicate reliable data as all subjects (N = 34) completed Cogstate baseline testing, while completion and performance checks indicate that 100 % of subjects completed testing and complied with test requirements. The majority (85 %) exhibited normal function compared with age peers. Preliminary analysis of CSF biomarkers (folate, homocysteine, 8-isoprostane, and myelin basic protein) similarly reveals values at baseline within expected normal ranges.
The first month of induction therapy for ALL is a reliable baseline for detecting treatment-induced changes in neurocognitive functioning. Consequently, serial data collection might identify subgroups of ALL patients at increased risk for neurocognitive decline, warranting proactive interventions to improve their level of functioning both during treatment and into survivorship.
在急性淋巴细胞白血病(ALL)幸存者中,经常会在智力、注意力、处理速度、工作记忆、学习和记忆等领域观察到神经认知障碍。然而,很少有人研究治疗最初几个月内神经认知功能的治疗诱导变化。此外,治疗期间的功能障碍可能先于脑脊液(CSF)中测量的生物标志物的变化。识别神经认知功能的急性下降以及预测性基因型或生物标志物,可以指导保护性干预措施的治疗试验。
本研究在一项达纳-法伯癌症研究所ALL联盟试验中,在白血病治疗的2年期间及之后的六个时间点,使用Cogstate计算机化测试组前瞻性评估ALL患者的神经认知功能(工作记忆、执行功能、学习、处理速度和注意力),同时收集脑脊液。
诱导化疗前3周收集的基线数据表明数据可靠,因为所有受试者(N = 34)都完成了Cogstate基线测试,而完成情况和性能检查表明100%的受试者完成了测试并符合测试要求。与年龄相仿的同龄人相比,大多数(85%)表现出正常功能。脑脊液生物标志物(叶酸、同型半胱氨酸、8-异前列腺素和髓鞘碱性蛋白)的初步分析同样显示基线值在预期正常范围内。
ALL诱导治疗的第一个月是检测治疗引起的神经认知功能变化的可靠基线。因此,连续数据收集可能会识别出神经认知功能下降风险增加的ALL患者亚组,有必要采取积极干预措施,以改善他们在治疗期间和存活期的功能水平。