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

评估接受儿童白血病治疗的拉丁裔神经认知差异的综合方法。

• 批准号: 10651850
• 负责人: Austin L Brown
• 金额: $ 61.46万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651850
• 关键词: Acceleration; Accounting; Acculturation; Acute Lymphocytic Leukemia; Acute leukemia; Address; Adult; Aftercare; Attention; Biological; Biological Factors; Child; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Clinical; Clinical Management; Clinical Oncology; Data; Diagnosis; Disparity; Doctor of Philosophy; Education; Employment; English Language; Enrollment; Environment; Epidemiologist; Epidemiology; Ethnic Origin; Ethnic Population; Event; Foundations; Funding; General Population; Genetic; Geographic Locations; Goals; Grant; Incidence; Individual; Infrastructure; Injury; Intervention; Latino; Latino Population; Leukemia Acute Lymphoblastic Chemotherapy; Longitudinal cohort; Malignant Childhood Neoplasm; Measures; Modeling; Native American Ancestry; Neighborhoods; Neurocognitive; Neurocognitive Deficit; Neuropsychology; Newly Diagnosed; Outcome; Participant; Patients; Performance; Phenotype; Population; Principal Investigator; Quality of life; Relapse; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Seizures; Short-Term Memory; Socioeconomic Factors; Socioeconomic Status; Survivors; Symptoms; Time; Treatment-related toxicity; Work; Youth; bilingualism; cerebrovascular; cohort; design; disparity reduction; economic outcome; ethnic disparity; executive function; experience; health disparity; improved; improved outcome; inattention; multi-ethnic; multidisciplinary; neurotoxic; neurotoxicity; non-genetic; novel; patient population; processing speed; protective factors; recruit; response; social health determinants; socioeconomics; survivorship; translational potential; treatment adherence; treatment comparison; treatment disparity; treatment response; white matter injury

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.

项目概要/摘要 拉丁裔儿童急性淋巴细胞白血病 (ALL) 的发病率有所增加，而且存在差异 治疗反应、复发和生存。然而，迄今为止，很少有研究评估 持续的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未完全得到解决。 由非遗传因素解释，例如治疗依从性的差异。事实上，生物因素 促成这些结果：美洲原住民的遗传血统与拉丁裔的复发有关 与 ALL 相关，并且与治疗期间的神经毒性有关。在这项工作的基础上，我们探索了两个悬而未决的问题 问题：1) 被诊断患有 ALL 的拉丁裔儿童的神经认知缺陷负担与 非拉丁裔儿童，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) 队列在以下人群中进行深度神经认知表型分析 被诊断并接受 ALL 治疗的人口子集 (N=400) – 特别关注拉丁裔，他们 超过正在进行的队列的 50%。我们将从诊断中模拟神经认知表现 诊断后 7 年，采用加速纵向队列设计，其中包括每年 评估对象： 1) 资助第一年新诊断的患者（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 被诊断患有 ALL 的儿童的神经认知结果模型，例如社会经济指标 地位（SES）、文化适应、英语语言能力和遗传血统。我们的研究目标是：1） 描述被诊断患有 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以及拉丁裔文化适应水平的影响； 3) 评估遗传血统对确诊儿童神经认知表现的相对贡献 与所有。我们方法的优势包括严格的初步数据、用于注册的招聘基础设施 诊断患有 ALL 的拉丁裔患者，作为我们正在进行的重拨队列的一部分收集的现有数据和样本， 无与伦比的研究环境以及种族和社会经济的地理区域 各种各样的。该提案对于改善临床管理具有重大转化潜力 该人群的神经认知结果，因为它将识别有神经认知困难风险的儿童，并在 最需要干预、治疗/生存的关键点，干预策略可能有助于 减轻神经认知结果和干预目标的差异。