IMPACT OF LEUKEMIA TREATMENT ON THE CNS AND DEVELOPMENT

白血病治疗对中枢神经系统和发育的影响

• 批准号: 2881168
• 负责人: KRISTINE L KAEMINGK
• 金额: $ 42.83万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2881168
• 关键词: academic achievement; acute lymphocytic leukemia; adolescence (12-20); antineoplastics; behavioral /social science research tag; biomarker; brain injury; cerebrospinal fluid; child (0-11); child psychology; clinical research; cognition disorders; drug adverse effect; drug screening /evaluation; human subject; neoplasm /cancer chemotherapy; neural information processing; phospholipids

DESCRIPTION (adapted from investigator's abstract): The goal of this work is to determine whether we can identify the children with acute lymphoblastic leukemia (ALL) who will have cognitive and academic problems using markers of central nervous system (CNS) injury obtained during treatment. Although declines in cognitive and academic function have been linked to CNS treatment in many studies, some ALL survivors exhibit significant declines while others do not. What accounts for this variability? Our recent findings suggest that changes in CSF phospholipid composition during treatment are related to subsequent cognitive and academic function. Based on our preliminary studies and available literature, the investigators believe that CNS injury has both direct and indirect effects on cognitive and academic function and that one indirect effect is a result of the impact of CNS injury on CNS processing speed. Thus, they will examine relationships between CSF markers of CNS injury, processing speed, and cognitive and academic abilities using latent variable and structural equation models. This prospective longitudinal study will follow 90 children with ALL who are age 3 to 13 years of age at diagnosis and treated according to Pediatric Oncology Group Protocol with triple intrathecal chemotherapy and intermediate dose systemic methotrexate. CSF concentration of 3 phospholipids (sphingomyelin, phosphatidylcholine, lysophosphaditylcholine) and cardiolipin will be used as markers of CNS injury. Cognitive and academic abilities will be evaluated at diagnosis and 1, 2,and 3 years after diagnosis. The investigators will use growth curve analysis to estimate each child's initial status and rate of change on cognitive and academic measures. They hypothesize that there will be (1) A significant negative relationship between CSF markers and performance on cognitive and academic measures; (2) A significant negative relationship between CSF markers and processing speed; and (3) A significant positive relationship between processing speed and cognitive and academic performance. Variables that may be related to cognitive outcomes will also be included in measurement models. These include the child's age at diagnosis or evaluation, sex, baseline abilities, school attendance and educational services and socioeconomic status. A sibling comparison group will be followed to allow estimation of loss of abilities associated with ALL and its treatment and identify cognitive abilities that may be particularly vulnerable. If the study can identify children at risk for cognitive and academic problems, those most in need of assistance can be provided with educational services and evaluation interventions.

描述（根据调查员的摘要进行改编）：这项工作的目的是 确定我们是否可以识别患有急性淋巴细胞的儿童 白血病（所有）将使用标记的认知和学术问题 治疗期间获得的中枢神经系统（CNS）损伤。虽然 认知和学术功能的下降与中枢神经系统治疗有关 在许多研究中，一些所有幸存者都表现出显着下降，而 不要。什么是这种可变性？我们最近的发现表明 治疗过程中CSF磷脂组成的变化与 随后的认知和学术功能。基于我们的初步研究 和可用的文献，调查人员认为CNS受伤都有 直接和间接对认知和学术功能的影响 间接效应是中枢神经系统损伤对中枢神经系统处理的影响的结果 速度。因此，他们将检查中枢神经系统损伤的CSF标记之间的关系， 使用潜在变量的处理速度以及认知和学术能力 和结构方程模型。这项前瞻性纵向研究将遵循 90名年龄3至13岁的儿童诊断并接受治疗 根据小儿肿瘤学组协议，具有三重鞘内。 化学疗法和中等剂量全身甲氨蝶呤。 CSF的浓度 3个磷脂（鞘磷脂，磷脂酰胆碱，溶血磷脂） 心脂蛋白将用作中枢神经系统损伤的标志。认知和学术 诊断后的能力将在诊断后进行1、2和3年进行评估。 研究人员将使用成长曲线分析来估计每个孩子的 认知和学术措施的最初状态和变化率。他们 假设将（1）（1） CSF标记和认知和学术措施的表现； （2）a CSF标记与处理速度之间的显着负相关；和 （3）处理速度与认知之间的显着正相关关系 和学习成绩。可能与认知结果有关的变量 也将包括在测量模型中。这些包括孩子的年龄 诊断或评估，性别，基线能力，上学和 教育服务和社会经济地位。兄弟姐妹比较组将 遵循以允许估计与全部相关的能力丧失 它的治疗并确定可能特别是 易受伤害的。该研究是否可以识别有认知和认知风险的儿童 学术问题，最需要帮助的人可以提供 教育服务和评估干预措施。