Exploring Age Differences in Patient Reported Cognitive Function Trajectories among Hematopoietic Stem Cell Transplant and Chimeric Antigen Receptor T-cell patients and Linking Two Key Measures

探索造血干细胞移植和嵌合抗原受体 T 细胞患者报告的认知功能轨迹的年龄差异，并将两个关键指标联系起来

• 批准号: 10593018
• 负责人: Rachel Nicole Cusatis
• 金额: $ 42.9万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593018
• 关键词: Address; Adult; Aftercare; Age; Attention; Blood; Bone Marrow Transplantation; CAR T cell therapy; Clinical; Collaborations; Collection; Data; Databases; Disease; Disparity; Elderly; Ensure; Ethnic Origin; European Organization for Research and Treatment of Cancer; Exhibits; Funding; General Population; Health; Hematological Disease; Hematopoietic Stem Cell Transplantation; Household; Impaired cognition; Income; Individual; Information Systems; Infrastructure; Infusion procedures; Link; Lymphoma; Malignant - descriptor; Measurement; Measures; Memory; Mental Depression; Methods; Modeling; Non-Malignant; Outcome; Outcome Measure; Patient Outcomes Assessments; Patients; Pattern; Population; Psyche structure; Psychometrics; Quality of life; Questionnaires; Race; Recommendation; Registries; Reporting; Research; Respondent; Sample Size; Sampling; Sickle Cell Anemia; Site; Socioeconomic Status; Standardization; Subgroup; Survivors; Symptoms; System; Testing; Transplant Recipients; Transplantation; United States; United States National Institutes of Health; Validation; Walking; age difference; chimeric antigen receptor T cells; cognitive function; computerized; curative treatments; ethnic disparity; experience; flexibility; hematopoietic cell transplantation; human old age (65+); international center; leukemia; novel; older patient; patient population; post-transplant; racial disparity; side effect; social; socioeconomic disparity; socioeconomics; survivorship; therapy development; tool; verbal

ABSTRACT Two established therapies to control and/or cure many hematologic diseases are hematopoietic cell transplantation (HCT) and Chimeric antigen receptor t-cell (CAR-T) treatment. In the last few years, there are increasing number of older patients receiving both treatments. Cognitive dysfunction, a common and serious side effect of HCT and CAR-T, was associated with older age. Patient-reported outcomes (PROs), or patient reports of their own symptoms and functioning without interpretation by anyone else, are critical to better understand patients' symptom trajectories, yet very few studies assess PROs among CAR-T patients. Small sample size and single-site studies are limited in their ability to understand potential age differences and even less among racially or socioeconomically diverse older survivors, leading to urgency for PROs from larger more representative data, such as a registry. The Center for International Blood and Marrow Transplant Research (CIBMTR) is an NIH-funded research collaboration that maintains a clinical outcome registry for HCT and CAR-T recipients and, beginning in 2016, developed a strategy and infrastructure for the routine collection of PROs. Patient-Reported Outcomes Measurement Information System (PROMIS) measures were chosen for their flexibility in sets of tools, rigorous testing, and translatability across other diseases and populations. Unlike many other available PRO measures, PROMIS measures are assessed for differences in how items are interpreted across different groups, such as by race/ethnicity and age, known as differential item functioning (DIF). However, the PROMIS cognitive function measure has only been assessed for DIF in 8 of 32 items. Previous research in HCT most often used a different measure to assess cognitive function: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC). A psychometric analysis known as linking has been used to develop crosswalk tables to directly compare PRO measures, like PROMIS depression, but has yet to link PROMIS to EORTC. Using data on the U.S. general population from an online panel, specific aim 1 will be the first study to use psychometric analysis to assess DIF for the full item bank of PROMIS cognitive function measure by age, race/ethnicity, and income and produce a crosswalk table to directly compare scores on the PROMIS and EORTC cognitive function measures. Using CIBMTR data, specific aim 2 will use linear mixed modeling to assess cognitive function by age and explore potential racial/ethnic and SES disparities among older patients. This project will produce: (1) recommendations for use of cognitive function measures in CIBMTR registry; (2) a crosswalk table directly linking PROMIS and EORTC; (3) a novel description of cognitive function trajectories of HCT and CAR-T patients by age; (4) explore racial/ethnic and socioeconomic disparities in PROs among older HCT and CAR-T patients. This project will provide preliminary data for an R01 proposal to assess disparities in survivorship experience using large registry database and, if necessary, inform intervention development to mitigate such disparities.

抽象的 控制和/或治愈许多血液疾病的两种既定疗法是造血细胞 移植（HCT）和嵌合抗原受体T细胞（CAR-T）治疗。近几年来，有 接受这两种治疗的老年患者数量不断增加。认知功能障碍是一种常见且严重的疾病 HCT 和 CAR-T 的副作用与年龄有关。患者报告的结果 (PRO)，或患者 在没有任何其他人解释的情况下报告自己的症状和功能对于更好地进行至关重要 了解患者的症状轨迹，但很少有研究评估 CAR-T 患者的 PRO。小的 样本量和单中心研究的能力有限，无法理解潜在的年龄差异，甚至 在种族或社会经济多样化的老年幸存者中较少，导致迫切需要来自更大的 PRO 更具代表性的数据，例如注册表。国际血液和骨髓移植中心 Research (CIBMTR) 是一项由 NIH 资助的研究合作项目，负责维护 HCT 的临床结果登记 和 CAR-T 接受者，并从 2016 年开始，为常规收集制定了战略和基础设施 PRO 的数量。选择患者报告结果测量信息系统 (PROMIS) 测量 它们在工具集上的灵活性、严格的测试以及在其他疾病和人群中的可转化性。不像 许多其他可用的 PRO 措施、PROMIS 措施都根据项目的差异进行评估 跨不同群体进行解释，例如按种族/民族和年龄，称为差异项目功能 （DIF）。然而，PROMIS 认知功能测量仅在 32 个项目中的 8 个项目中评估了 DIF。 先前的 HCT 研究最常使用不同的测量方法来评估认知功能：欧洲 癌症研究与治疗组织生活质量问卷 (EORTC)。心理测量学 称为链接的分析已用于开发人行横道表以直接比较 PRO 措施，例如 PROMIS 抑郁症，但尚未将 PROMIS 与 EORTC 联系起来。使用美国总人口的数据 在线小组，具体目标 1 将是第一个使用心理测量分析来评估整个项目的 DIF 的研究 PROMIS 认知功能库按年龄、种族/民族和收入进行测量，并生成人行横道表 直接比较 PROMIS 和 EORTC 认知功能测量的分数。使用 CIBMTR 数据， 具体目标 2 将使用线性混合模型来评估按年龄划分的认知功能并探索潜力 老年患者中的种族/民族和社会经济地位差异。该项目将产生：（1）使用建议 CIBMTR 注册中的认知功能测量； (2) 直接连接 PROMIS 和 EORTC 的人行横道表； (3) 按年龄划分的 HCT 和 CAR-T 患者认知功能轨迹的新颖描述； (4)探索 老年 HCT 和 CAR-T 患者中 PRO 的种族/民族和社会经济差异。该项目将 为 R01 提案提供初步数据，以使用大数据评估幸存者经验的差异 登记数据库，并在必要时通知干预措施的制定，以缩小这种差异。