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

项目总结/摘要 拉丁裔儿童急性淋巴细胞白血病（ALL）的发病率增加， 治疗反应、复发和生存率。然而，到目前为止，很少有研究评估 持续性神经认知症状对拉丁裔幸存者教育和经济结果的影响什么 我们的小组和其他人已经证明，患有ALL的拉丁裔儿童之间的差异并不完全 非遗传因素解释，如治疗依从性的差异。事实上，生物因素 有助于这些结果：美洲原住民的遗传血统与拉丁美洲人的复发有关 与ALL相关，并与治疗期间的神经毒性有关。从这项工作的建设，我们探讨两个悬而未决的问题， 问题：1）相对于被诊断为ALL的拉丁裔儿童， 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ALL幸存者神经认知差异的因素。我们将利用我们正在进行的 减少急性白血病的种族差异（REDIAL）队列，以在 被诊断并接受ALL治疗的人群的一个子集（N=400）-特别关注拉丁美洲人， 超过了正在进行的队列的50%。我们将从诊断中模拟神经认知表现 通过采用加速纵向队列设计，诊断后7年， 评估：1）补助金第一年的新诊断患者（第1波，n = 200）;和2）幸存者 诊断后3-7年（第2波，n = 200）。我们还纳入了尚未包括在 诊断为ALL的儿童的神经认知结果模型，如社会经济指标， 社会经济地位（SES），文化适应，英语能力和遗传血统。我们的研究目标是：1） 描述被诊断为ALL的拉丁裔儿童的神经认知表现轨迹; 2）检查 临床，个人和社区社会经济因素的影响，以及拉丁美洲人的文化适应水平; 以及3）评估遗传祖先对诊断为神经认知障碍的儿童的神经认知表现的相对贡献。 与所有。我们的方法的优势包括严格的初步数据， 诊断为ALL的拉丁裔患者，作为我们正在进行的REDIAL队列的一部分收集的现有数据和样本， 一个无与伦比的研究环境，一个在种族和社会经济上 多样化。这一建议具有显著的转化潜力，以改善临床管理， 这一人群的神经认知结果，因为它将识别出有神经认知困难风险的儿童， 最需要干预，在治疗/生存的关键点时，干预策略可能有助于 减轻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.