Impact of Comorbidities on Outcomes of Allogeneic Transplantation

异基因造血细胞移植（HCT）是一种潜在的治疗各种血液病的方法。 疾病然而，许多可能从HCT中获益的患者不符合条件， 由于合并症和年龄而进行手术。随着低强度治疗方案的发展， 清髓性HCT后支持治疗的改善，老年患者数量的增加， 接受了同种异体血细胞比容。我发表了第一份报告， 合并症在预测HCT结果中的重要性。然后我又开发了一种更灵敏的新工具 评估同种异体HCT接受者特有的合并症。HCT特异性合并症指数（HCTCI） 有助于更好地了解合并症对HCT结果的影响，并形成了此基础 提议该建议的重点是进一步评估和开发合并症的预后价值 对HCT受者的结局进行评估，最终目的是建立一个普遍适用的合并症指数。 在指导阶段，我收集了来自五个机构的3331名移植患者的数据， 证实了HCT-CI的多中心有效性。我还证明了年龄对 非清髓性HCT结局，但>50岁患者的死亡风险较高， 清髓性方案。将加权年龄间隔对HCT结局影响的评分添加到 HCT-CI以形成复合评分。这些研究的结果引导我进入独立 该阶段将解决三个平行的主要目标。首先，我将检验结果预测的同质性， 各机构的HCT-CI和验证HCT-CI/年龄结局评分的预测影响 在来自国际血液和骨髓移植中心的大型患者数据集（n= 15，000）中， 研究（CIBMTR）。其次，我将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疾病，以及对生活质量的影响 HCT后使用HCT-CI/年龄评分以及个体合并症负担。这将涉及双方 对既往移植患者的病历进行回顾性分析， 临床试验纳入更多患者，并确保 合并症。第三，我将前瞻性地研究三种不同的方法， 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。

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. I have published the first report describing the importance of comorbidities in predicting HCT outcomes. I then went on to develop a more sensitive new tool to assess comorbidities specific for recipients of allogeneic HCT. The HCT-specific-comorbidity index (HCTCI) served to better understand the impact of comorbidities on HCT outcomes and it forms the basis for this proposal. This 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, I have collected data from 3331 patients transplanted at five institutions and confirmed the multi-center validity of the HCT-CI. I also demonstrated lack of impact of age on nonmyeloablatlve HCT outcomes but higher risks for mortality among patients of >50 years given myeloablative regimens. Scores weighting the impact of age intervals on HCT outcomes were added to the HCT-CI to form composite scores. Results of these studies have guided me to proceed into the Independent Phase, which will address three parallel major aims. First, I will test homogeneity of outcome prediction per the HCT-CI across institutions and validation ofthe predictive impacts ofthe HCT-CI/age scores of outcomes in a large dataset (n=15,000) of patients from the Center of International Blood and Marrow Transplantation Research (CIBMTR). Second, I will assess the biological impact of comorbidities on causes of death, particularly those associated with acute graft-versus-host-disease and organ failures, and on quality of life after HCT using the HCT-CI/age scores as well as individual comorbidity burden. 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. Third, I will prospectively investigate three different methods for 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.