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.

总结 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 尽管在过去50年中情况有所改善，但种族差距依然存在。尤其是拉丁裔的发病率最高， 是美国白血病存活率最低的国家之一。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，如有限的医疗保健 access.导致治疗相关毒性增加的宿主药物基因组学和其他生物学因素 是造成结果中种族差异的一个关键原因，但研究不足。不良结果既来自直接原因， 治疗相关的发病率和死亡率，以及提供足够强度的抗- 白血病治疗 该P20计划的总体目标是减少拉丁裔儿童和青少年之间的结果差异 通过确定导致毒性增加的宿主生物因素，并为建立 第一个致力于儿科白血病的卓越研究专业计划（SPORE）。两 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， 拉丁裔。最终的SPORE将通过（1）实施预防和治疗策略来扩大这项工作 和（2）研究其他临床上有影响的治疗相关毒性的种族差异。该计划将 通过行政核心（核心A）进行管理。生物标本将由核心B处理， 统计分析将由核心C提供。发展研究计划将促进发展 创新试点项目，旨在了解和/或减少所有结果中基于族裔的差异。我们 将利用减少急性白血病种族差异（REDIAL）联盟，包括6种癌症 位于美国西南部，它将提供3,000个临床数据，骨髓， 来自近2,000名新诊断为ALL的儿童和青少年的血液和脑脊液样本， 以下两个新的综合项目。 我们的协同整合团队将定义与肝毒性相关的关键生物学因素， 神经毒性，种族结果差异的重要贡献者。更广泛地说，该计划将进一步 加强和扩大REDIAL联盟，其宝贵的种族多样性数据集和生物储存库， 并将其用于风险预测模型的开发，该模型可识别有毒性风险的拉丁美洲患者， 阐明了潜在的生物学机制。这项工作将为未来的SPORE奠定基础， 研究ALL治疗的其他毒性，并将这些发现转化为有效的 干预策略。这种有效的货币投资将导致结果的显著减少 拉丁裔儿童和青少年与ALL的差异。