Incorporating patient reported outcomes into individualized prognostication tools for survival and quality of life in transplant patients

摘要 造血细胞移植（HCT）可以治愈许多患者，但通常有晚期效应的风险， 生活质量（QOL）严重受损。虽然工具可用于帮助患者和临床医生 预测HCT后早期的个体化结局（如国际血液和骨髓中心） 研究（CIBMTR）1年生存计算器），这些目前几乎完全基于临床和 人口统计学因素，并预测生存，但不是生活质量。尽管最近的研究表明，前HCT患者- 报告的结果（PRO）对生存率和生活质量都有显著的预测作用，很少有移植中心常规 收集这些。缺乏系统的PRO收集的令人信服的原因包括缺乏关于 最准确的测量，对PRO提供的新信息超过临床医生判断的怀疑，以及不确定性 关于如何将它们与当前的HCT工具集成。本研究的目标是通过以下方式解决这些缺陷： 从现有的PRO措施中确定一套简短的歧视性PRO问题，并将其纳入 预测个体化生存率和长期生活质量的工具。我们的三个具体目标是：1）确定 移植前PRO元素的最短集合，其将保持与移植后存活的显著关联， 移植并使用它来增强和扩展现有的CIBMTR 1年生存计算器，2）开发一个 一套新的计算器，可预测HCT后1年的QOL，3）通过合并两者预测长期QOL HCT前后PRO和其他HCT后并发症。我们将通过利用 由NHLBI资助的前瞻性临床研究收集的独特PRO数据 CIBMTR和附属的血液和骨髓移植临床试验网络（BMT CTN）。这些 各组织大力鼓励二次分析，并已确定了实现这一目标的机制。 我们将纳入7项使用FACT-BMT、SF 36或两者收集PRO数据的研究。总 样本为3236例，考虑到这种罕见的干预措施，这是一个非常大的患者数量。这一群体捕获了一个 在15年的时间里，成年患者的广泛代表性。除了PRO数据外，每项研究还 全面和一致收集的临床数据，包括HCT前患者和疾病变量， 移植特征和HCT后结果。每项研究均包括基线PRO数据（HCT前），以及 在多个HCT后时间点（长达5年）收集PRO。我们的调查结果 通过增强和标准化HCT工具，对接受HCT的患者产生直接和显著的影响 对于HCT后的生存率和QOL，个体患者的生存率。

ABSTRACT Hematopoietic cell transplantation (HCT) can cure many patients, but often with the risk of late effects and significantly impaired quality of life (QOL). Whilst tools are available to assist patients and clinicians in predicting individualized outcomes early post-HCT (such as the Center for International Blood and Marrow Research (CIBMTR) 1-year survival calculator), these are currently almost exclusively based on clinical and demographic factors, and predict survival, but not QOL. Despite recent studies showing that pre-HCT patient- reported outcome (PRO)s are significantly predictive of both survival and QOL, few transplant centers routinely collect these. Compelling reasons for the lack of systematic PRO collection include lack of agreement on the most accurate measure, skepticism that PROs offer novel information over clinician judgment, and uncertainty regarding how to integrate them with current HCT tools. The goal of this study is to address these deficits by identifying a short set of discriminating PRO questions, from existing PRO measures, and to incorporate these into tools to predict individualized survival and long term QOL. Our 3 specific aims are: 1) determine the shortest set of pre-transplant PRO elements which will maintain a significant association with survival post- transplant and use this to enhance and extend the existing CIBMTR 1-year survival calculator, 2) develop a new set of calculators which predict 1-year post-HCT QOL, and 3) predict long-term QOL by incorporating both pre-and post-HCT PROs and other post-HCT complications. We will pursue these aims by leveraging the unique PRO data which has been collected on prospective clinical studies performed by the NHLBI-funded CIBMTR and the affiliated Blood and Marrow Transplant Clinical Trials Network (BMT CTN). These organizations strongly encourage secondary analyses and have defined mechanisms by which to achieve this. We will include seven studies which collected PRO data using either the FACT-BMT, SF36 or both. The total sample is 3236, a very large number of patients when considering this rare intervention. This cohort captures a broad representation of adult patients over a 15-year period. In addition to PRO data each study has comprehensive and consistently collected clinical data, including pre-HCT patient and disease variables, transplant characteristics and post-HCT outcomes. Every study includes baseline PRO data (pre-HCT), and PROs collected at multiple post-HCT time points (up to five years). The results from our investigation will have an immediate and significant impact on patients undergoing HCT by enhancing and standardizing HCT tools for individual patient prognostication, both for survival and QOL post-HCT.