An Integrative Approach to Evaluate Neurocognitive Disparities in Latinos Undergoing Treatment for Childhood Leukemia.

项目摘要/摘要 拉美裔儿童急性淋巴细胞性白血病(ALL)的发病率增加，并存在差异 在治疗反应、复发和存活率方面。然而，到目前为止，很少有研究评估 持续神经认知症状对拉丁裔幸存者的教育和经济结果的影响。什么 我们小组和其他人已经证明，拉美裔儿童与ALL儿童之间的差距并不完全 这可以用非遗传因素来解释，比如治疗依从性的差异。事实上，生物因素 促成这些结果：印第安人的基因血统与拉美人的复发有关 与ALL有关，并与治疗期间的神经毒性有关。从这部作品出发，我们探索了两个未得到回答的问题 问题：1)与ALL相关的拉丁裔儿童的神经认知缺陷的负担是什么 非拉丁裔儿童，以及2)临床、社会经济、文化和生物学的相对贡献是什么 解释儿童所有幸存者神经认知差异的因素。我们将利用我们正在进行的 减少急性白血病(REDIAL)队列中的种族差异以进行深度神经认知表型分析 人群中的一部分(N=400)为所有人诊断和治疗-特别关注拉丁裔，他们使 增加了正在进行的队列的50%以上。我们将通过诊断来模拟神经认知表现 通过采用加速纵向队列设计进行7年的诊断后，包括每年 对以下方面的评估：1)赠款第一年的新诊断患者(第1波，n=200)；2)幸存者 诊断后3~7年(第2波，n=200)。我们还纳入了尚未纳入的因素 诊断为ALL的儿童的神经认知结果的模型，如社会经济指标 身份(SES)、文化适应、英语熟练程度和遗传血统。我们的研究目标是：1) 描述被诊断为急性淋巴细胞白血病的拉丁裔儿童的神经认知表现轨迹；2)检查 临床、个人和邻里社会经济因素的影响，以及拉美裔的文化适应程度； 3)评估遗传血统对确诊儿童的神经认知能力的相对贡献 和所有人在一起。我们方法的优势包括严格的初步数据、招生的招聘基础设施 拉丁裔患者被诊断为ALL，现有的数据和样本是我们正在进行的重拨队列的一部分， 无与伦比的研究环境和种族和社会经济的地理区域 多种多样。这项建议具有显著的翻译潜力，以改善临床管理 这一人群的神经认知结果，因为它将确定有神经认知困难风险的儿童和 最需要干预，治疗/生存的关键点，当干预策略可能有助于 缓解神经认知结果的差异，以及干预的目标。

PROJECT SUMMARY/ABSTRACT Latino children experience increased incidence of acute lymphoblastic leukemia (ALL), as well as disparities in treatment response, relapse, and survival. However, to date, there have been few studies evaluating the impact of persistent neurocognitive symptoms on educational and economic outcomes in Latino survivors. What has been demonstrated by our group and others is that disparities among Latino children with ALL are not fully explained by non-genetic factors, such as differences in treatment adherence. In fact, biological factors contribute to these outcomes: Native American genetic ancestry has been implicated in relapse among Latinos with ALL and is related to neurotoxicity during treatment. Building from this work, we explore two unanswered questions: 1) what is the burden of neurocognitive deficits among Latino children diagnosed with ALL relative to non-Latino children, and 2) what is the relative contribution of clinical, socioeconomic, cultural, and biological factors in explaining neurocognitive disparities among childhood ALL survivors. We will leverage our ongoing Reducing Ethnic Disparities in Acute Leukemia (REDIAL) cohort to conduct deep neurocognitive phenotyping in a subset of the population (N=400) diagnosed and treated for ALL – with a particular focus on Latinos, who make up more than 50 percent of the ongoing cohort. We will model neurocognitive performance from diagnosis through 7 years post-diagnosis by employing an accelerated longitudinal cohort design, which includes annual assessments for: 1) newly diagnosed patients in the first years of the grant (Wave 1, n = 200); and 2) survivors who are 3-7 years post diagnosis (Wave 2, n = 200). We also incorporate factors that have yet to be included in models of neurocognitive outcomes among children diagnosed with ALL, such as measures of socioeconomic status (SES), acculturation, English-language proficiency, and genetic ancestry. Our research aims are to: 1) characterize the trajectory of neurocognitive performance in Latino children diagnosed with ALL; 2) examine the impact of clinical, individual and neighborhood socioeconomic factors, and level of acculturation among Latinos; and 3) assess the relative contribution of genetic ancestry to neurocognitive performance in children diagnosed with ALL. Strengths of our approach include rigorous preliminary data, a recruitment infrastructure for enrolling Latino patients diagnosed with ALL, existing data and samples collected as part of our ongoing REDIAL cohort, an unparalleled research environment, and a geographical region that is ethnically and socioeconomically diverse. This proposal has significant translational potential to improve the clinical management of neurocognitive outcomes in this population, as it will identify children at risk for neurocognitive difficulties and in greatest need of intervention, critical points in treatment/survivorship when intervention strategies may help to mitigate disparities in neurocognitive outcomes, and targets for intervention.