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已建立的疗法是造血细胞移植。 移植（HCT）和嵌合抗原受体t细胞（CAR-T）治疗。在过去的几年里， 越来越多的老年患者接受这两种治疗。认知功能障碍，一种常见而严重的 HCT和CAR-T的副作用与年龄相关。患者报告结局（PRO），或患者 报告自己的症状和功能，而不需要其他任何人的解释，对于更好地 了解患者的症状轨迹，但很少有研究评估CAR-T患者中的PRO。小 样本量和单点研究在理解潜在年龄差异方面的能力有限， 在种族或社会经济多样化的老年幸存者中， 更有代表性的数据，如注册表。国际血液和骨髓移植中心 研究（CIBMTR）是NIH资助的研究合作，维护HCT的临床结局登记 和CAR-T接受者，并从2016年开始制定了常规收集的战略和基础设施， 选择患者报告结局测量信息系统（PROMIS）测量， 他们在工具集，严格的测试和跨其他疾病和人群的可移植性的灵活性。不像 许多其他可用的PRO措施，PROMIS措施评估项目如何差异， 在不同的群体中进行解释，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。 以前的HCT研究最常使用不同的测量来评估认知功能：欧洲人 癌症研究和治疗组织生活质量问卷（EORTC）。了一个心理测验 被称为链接的分析已被用于开发人行横道表，以直接比较PRO措施，如 PROMIS抑郁症，但尚未将PROMIS与EORTC联系起来。使用美国一般人口的数据， 一个在线小组，具体目标1将是第一个使用心理测量分析来评估DIF的完整项目的研究 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认知功能测量的评分。使用CIBMTR数据， 具体目标2将使用线性混合模型来评估不同年龄的认知功能，并探索潜力 老年患者中的种族/民族和SES差异。本项目将产生：（1）使用建议 CIBMTR登记的认知功能测量：（2）直接连接PROMIS和EORTC的人行横道表; (3)按年龄对HCT和CAR-T患者认知功能轨迹的新描述;（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R 01提案提供初步数据，以评估使用大型 登记数据库，并在必要时为干预措施的制定提供信息，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.