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

摘要 控制和/或治愈许多血液病的两种公认疗法是造血细胞。 移植(HCT)和嵌合抗原受体T细胞(CAR-T)治疗。在过去几年里，有 越来越多的老年患者同时接受这两种治疗。认知功能障碍，一种常见而严重的 Hct和CAR-T的副作用与年龄有关。患者报告的结果(PRO)或患者 在没有任何人解释的情况下，报告他们自己的症状和功能是更好地 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 样本量和单点研究在了解潜在的年龄差异甚至是 在种族或社会经济多元化的老年幸存者中较少，导致来自更大规模的专业人士的紧迫性 更具代表性的数据，如注册表。国际血液和骨髓移植中心 研究(CIBMTR)是由美国国立卫生研究院资助的一个研究合作项目，负责维护HCT的临床结果登记 和CAR-T接受者，并从2016年开始制定了例行收集的战略和基础设施 职业选手。患者报告的结果测量信息系统(PROIS)被选择用于 他们在成套工具中的灵活性、严格的测试以及跨其他疾病和人群的可译性。不像 许多其他可用的PRO措施，PROIS措施被评估如何项目的差异 跨不同群体的解释，如按种族/民族和年龄，称为差异项目功能 (Dif)。然而，在32个项目中，只有8个项目对Promis认知功能进行了评估。 之前对HCT的研究最常使用不同的测量方法来评估认知功能：欧洲 癌症研究和治疗组织生活质量问卷(EORTC)。心理测量学 称为链接的分析已被用于开发人行横道表格，以直接比较PRO措施，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 一个在线小组，特殊目标1将是第一个使用心理测量学分析来评估完整项目的DIF的研究 Promis银行根据年龄、种族/民族和收入来衡量认知功能，并制作一张人行横道表格 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将使用线性混合建模来评估年龄和开发潜力的认知功能 老年患者的种族/民族和自闭症患者的差异。该项目将产生：(1)使用建议 (2)直接连接PROMIS和EORTC的人行横道桌； (3)对HCT和CAR-T患者的认知功能轨迹按年龄进行新的描述；(4)探索 老年HCT和CAR-T患者PRO的种族/民族和社会经济差异。这个项目将 为R01提案提供初步数据，以评估生存体验方面的差异 登记册数据库，并在必要时通报干预措施的发展情况，以减少这种差异。

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.