Improving Outcome Disparities for Latino Children and Adolescents with Acute Lymphoblastic Leukemia

改善患有急性淋巴细胞白血病的拉丁裔儿童和青少年的结果差异

• 批准号: 10289493
• 负责人: Philip Lupo
• 金额: $ 112.29万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10289493
• 关键词: Accounting; Acute; Acute Lymphocytic Leukemia; Acute leukemia; Address; Adolescent; Behavioral; Biological; Biological Factors; Biology; Biometry; Blood; Bone Marrow; Cancer Center; Cerebrospinal Fluid; Child; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Clinical; Clinical Data; Clinical Treatment; Data Set; Development; Ethnic Origin; Etiology; Fostering; Foundations; Future; Genetic; Goals; Health; Hepatotoxicity; Hispanics; Incidence; Infrastructure; Inherited; Intervention; Investments; Latino; Malignant Childhood Neoplasm; Methotrexate; Modeling; Morbidity - disease rate; Neoadjuvant Therapy; Newly Diagnosed; Obesity; Outcome; Patients; Pharmacogenomics; Pharmacometabolomics; Pilot Projects; Prevention strategy; Process; Prospective cohort; Race; Recurrence; Relapse; Research; Research Project Grants; Risk; Risk Factors; Role; Sampling; Socioeconomic Status; Specialized Program of Research Excellence; Specimen Handling; Statistical Data Interpretation; Survival Rate; Testing; Toxic effect; Translating; Treatment outcome; Treatment-related toxicity; Tumor Biology; Variant; Vulnerable Populations; Work; acute toxicity; adverse outcome; base; biobank; data management; effective intervention; ethnic difference; ethnic disparity; ethnic diversity; health care availability; improved; improved outcome; innovation; leukemia; metabolomics; modifiable risk; mortality; neurotoxicity; novel; novel imaging technique; programs; racial and ethnic; racial and ethnic disparities; risk prediction model; social; social health determinants; treatment strategy; tumor; white matter

Summary Acute lymphoblastic leukemia (ALL) is the most common cancer in children and, although cure rates have improved over the past 50 years, ethnic disparities persist. In particular, Latinos have the highest incidence and among the lowest survival rates for leukemia in the U.S. The underlying causes of this disparity are multi-factorial, including differences in tumor and host biology, as well as social/behavioral factors such as limited healthcare access. Host pharmacogenomics and other biological factors resulting in increased treatment-related toxicities are a key and under-studied cause of ethnic disparities in outcomes. Adverse outcomes result both from direct treatment-associated morbidity and mortality, and from compromised ability to deliver sufficiently intensive anti- leukemic therapy. The overall goals of this P20 program are to reduce outcome disparities among Latino children and adolescents by identifying host biological factors that result in increased toxicities, and to lay the groundwork for establishment of the first Specialized Programs of Research Excellence (SPORE) devoted to pediatric leukemia. The two primary Research Projects will identify factors associated with risk for two key treatment-related toxicities, hepatotoxicity and neurotoxicity, which adversely impact treatment outcomes and occur disproportionately in Latinos. The eventual SPORE will expand upon this work by (1) pursuing prevention and treatment strategies and (2) investigating ethnic disparities in other clinically impactful treatment-related toxicities. The Program will be administered through the Administrative Core (Core A). Biospecimens will be processed by Core B, and statistical analysis will be provided by Core C. A Developmental Research Program will foster development of innovative pilot projects that aim to understand and/or reduce ethnicity-based disparities in ALL outcomes. We will leverage the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, comprising 6 cancer centers in the southwestern U.S., which will provide clinical data from 3,000 and clinical data, bone marrow, blood and cerebrospinal fluid samples from nearly 2,000 children and adolescents with newly diagnosed ALL for the following two novel and integrated Projects. Our synergistically integrated team will define key biological factors associated with hepatotoxicity and neurotoxicity, important contributors to ethnic outcome disparities. More broadly, this Program will further strengthen and expand the REDIAL Consortium, with its invaluable ethnically diverse dataset and biorepository, and model its use for development of risk prediction models that identify Latino patients at risk for toxicities and illuminate the underlying biology mechanisms. This work will form the foundation for a future SPORE that will investigate additional toxicities of ALL therapy, and translate these findings into development of effective intervention strategies. This efficient monetary investment will result in significant reductions in outcome disparities in Latino children and adolescents with ALL.

概括 急性淋巴细胞白血病（ALL）是儿童中最常见的癌症，尽管治愈率具有 在过去的50年中，种族差异得以改善。特别是，拉丁美洲人的发病率最高， 在美国白血病最低的生存率中，这种差异的根本原因是多因素的， 包括肿瘤和宿主生物学的差异以及社会/行为因素，例如有限的医疗保健 使用权。宿主药物基因组学和其他生物学因素，导致与治疗相关的毒性增加 是成果中种族差异的关键和研究不足的原因。不利的结果是直接导致的 与治疗相关的发病率和死亡率，以及造成足够密集抗的能力 白血病疗法。 该P20计划的总体目标是减少拉丁裔儿童和青少年的结果差异 通过识别宿主生物学因素，从而导致毒性增加，并为建立奠定基础 专门研究儿科白血病的第一个专业研究专业计划（Spore）。两个 主要研究项目将确定与两种关键治疗相关毒性风险相关的因素， 肝毒性和神经毒性，对治疗结果产生不利影响，并在 拉丁美洲人。最终的孢子将通过（1）追求预防和治疗策略来扩展这项工作 （2）调查其他临床影响的与治疗相关的毒性中的种族差异。该程序将 通过管理核心（核心A）进行管理。生物测量将由核心B处理，并且 统计分析将由CoreC提供。发展研究计划将促进 创新的试点项目旨在了解和/或减少所有结果中基于种族的差异。我们 将利用急性白血病（REDIAL）财团中的种族差异，包括6个癌症 美国西南部的中心将提供3,000和临床数据的临床数据，骨髓， 来自近2,000名儿童和青少年的血液和脑脊液样本，新诊断为 以下两个小说和综合项目。 我们的协同综合团队将定义与肝毒性和肝毒性相关的关键生物学因素 神经毒性，造成种族结果差异的重要因素。更广泛地，该计划将进一步 加强和扩大重复财团，其种族多样化的数据集和生物座位都有价值 并建模其用于开发风险预测模型的使用，这些模型识别有毒性风险的拉丁裔患者 阐明潜在的生物学机制。这项工作将构成未来的孢子的基础 研究所有疗法的其他毒性，并将这些发现转化为有效的发展 干预策略。这项有效的货币投资将大幅减少结果 拉丁裔儿童和青少年与所有人的差异。