Impact of Comorbidities on Outcomes of Allogeneic Transplantation

描述（由申请人提供）： 项目概述：异基因造血细胞移植（HCT）是一种治疗多种血液病的潜在疗法。然而，许多可能从HCT中获益的患者由于合并症和年龄而不适合进行该手术。随着降低强度方案的发展和清髓性HCT后支持性治疗的改善，越来越多的老年患者和合并症患者接受了同种异体HCT。 Sorror博士和他的合作者R. Diaconescu发表了第一份报告，描述了合并症在预测HCT结果中的重要性。Sorror博士继续开发了一种新的更敏感的工具来评估同种异体HCT接受者的合并症。HCT特异性合并症指数（HCT-CI）为更好地了解合并症对HCT结局的影响创造了独特的机会，它构成了本提案的基础。 该提案的重点是进一步评估和开发合并症对HCT接受者结局的预后价值，最终目标是创建一个普遍适用的合并症指数。 在指导阶段，HCT-CI的可靠性和有效性将在多个中心移植的患者中进行回顾性测试。此外，还将开发加权年龄间隔对HCT结局影响的评分，以形成HCT-CI的复合评分。 这些研究的结果将指导Sorror博士进入独立阶段，这将解决两个平行的主要目标。首先，将通过比较HCT评分，评估合并症对死亡原因的生物学影响，特别是与急性移植物抗宿主病和器官衰竭相关的死亡原因，以及HCT后的生活质量。 HCT-CI与来自共病-老化综合指数的那些比较。这将涉及既往移植患者病历的回顾性审查和前瞻性临床试验的分析，以纳入更多患者，并确保合并症影响的前瞻性再现性。 第二个目标是前瞻性研究三种不同的方法，旨在简化合并症数据的收集，并制定一个教育计划，由数据登记员评估合并症，从而促进更广泛的合并症评估在HCT中心。 相关性：该提案的目标是改善移植前对接受同种异体HCT治疗的恶性和非恶性血液疾病患者的生存和生活质量的预后评估，并最终建立一个普遍适用的合并症指数，这将有助于比较在不同学术中心进行的临床试验结果。 (End摘要）

DESCRIPTION (provided by applicant): Project Summary: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for various hematological diseases. However, many patients who could potentially benefit from HCT have been ineligible for the procedure due to comorbidities and age. With the development of reduced-intensity regimens and improvements in supportive care after myeloablative HCT, increasing numbers of elderly patients and those with comorbidities have been offered allogeneic HCT. Dr. Sorror, and a collaborator, Dr. R. Diaconescu, have published the first reports describing the importance of comorbidities in predicting HCT outcomes. Dr. Sorror went on to develop a new and more sensitive tool to assess comorbidities specific for recipients of allogeneic HCT. The HCT-specific-comorbidity index (HCT-CI) has created unique opportunities to better understand the impact of comorbidities on HCT outcomes and it forms the basis for this proposal. The proposal is focused on further evaluating and developing the prognostic value of comorbidities for outcomes in HCT recipients with the eventual aim of creating a universally applicable comorbidity index. During the Mentored Phase, the reliability and validity of the HCT-CI will be retrospectively tested among patients transplanted at multiple centers. In addition, scores weighting the impact of age intervals on HCT outcomes will be developed to form composite scores with the HCT-CI. Results of these studies will guide Dr. Sorror to proceed into the Independent Phase, which will address two parallel major aims. First, the biological impact of comorbidities on causes of death, particularly those associated with acute graft-versus-host disease and organ failures, and quality of life after HCT will be assessed comparing scores from the HCT-CI to those from the comorbidity-aging composite index. This will involve both retrospective reviews of medical records of previously transplanted patients and analyses of prospective clinical trials to include larger number of patients and to ensure prospective reproducibility of the impacts of comorbidities. The second aim will prospectively investigate three different methods aimed at simplifying collection of comorbidity data and develop an educational program for evaluation of comorbidities by data registrars and, thereby, facilitate the more wide-spread incorporation of comorbidity assessment at HCT centers. Relevance: The goal of the proposal is to improve pretransplant prognostic assessment of survival and quality of life in patients with malignant and non-malignant blood disorders who are treated with allogeneic HCT and eventually establish a universally applicable comorbidity index, which will facilitate comparing results of clinical trials conducted at different academic centers. (End of Abstract)