Impact of Comorbidities on Outcomes of Allogeneic Transplantation

项目概述：异基因造血细胞移植（HCT）是一种潜在的治疗方法， 各种血液病。然而，许多可能从HCT中获益的患者， 由于合并症和年龄不适合手术。随着低强度的发展， 清髓性HCT后的方案和支持性护理的改善，老年人数量增加 已经为患者和患有合并症的患者提供了同种异体HCT。Sorror博士和他的合作者Dr. R. Diaconescu发表了第一份报告，描述了合并症在预测HCT中的重要性 结果。Sorror博士继续开发一种新的更敏感的工具来评估特定于以下疾病的合并症： 同种异体HCT的接受者。HCT特异性合并症指数（HCT-CI）创造了独特的机会 以更好地了解合并症对HCT结果的影响，这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的预后价值， HCT接受者的结局，最终目的是建立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以下人群中进行回顾性测试： 在多个中心进行移植的患者。此外，加权年龄间隔对HCT影响的评分 将开发结果以形成HCT-CI的复合评分。这些研究的结果将指导 博士Sorror进入独立阶段，这将解决两个平行的主要目标。一是 合并症对死亡原因的生物学影响，特别是与急性移植物抗 宿主疾病和器官衰竭，以及HCT后的生活质量将进行评估， HCT-CI与来自共病-老化综合指数的那些比较。这将涉及对以下方面的回顾性审查： 既往移植患者的病历和前瞻性临床试验分析，包括 更多患者，并确保合并症影响的前瞻性再现性。的 第二个目标将前瞻性地研究三种不同的方法，旨在简化收集 合并症数据，并制定教育计划，由数据登记员评估合并症， 因此，有助于在HCT中心更广泛地纳入合并症评估。 相关性：该提案的目标是改善移植前生存预后评估， 接受同种异体移植治疗的恶性和非恶性血液病患者的生活质量 HCT，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的结果。

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.