Analysis of Morbidity and Mortality Among Hematopoietic Cell Transplantation Surv

描述（由申请人提供）：随着造血细胞移植（HCT）使用的增加和长期幸存者数量的相应增加，除了描述原发疾病复发和移植物抗宿主病（GVHD）之外，还需要更好地描述这一人群中晚期发病和死亡的原因。利用现有的基于人群的出院和死亡登记数据，我们现有的工作已经阐明了长期（2年）移植幸存者中严重心血管疾病的严重程度，并有助于更好地了解相关的hct前和hct相关的危险因素。我们现在建议将该方法扩展到全面检查华盛顿州（WA）居民和在弗雷德哈钦森癌症研究中心（FHCRC）接受治疗的2年HCT幸存者人群（n=2096, 53%异体）的所有其他重要健康结果。我们将特别关注严重的晚期肺部和感染性并发症以及第二种癌症，它们与心血管疾病一起在先前的研究中被确定为非复发相关死亡率的主要原因。该队列的hct前和hct相关暴露将与同期的州医院出院、死亡和癌症登记相关联。这将使我们能够：1)将HCT幸存者的转归率与来自一般人群的转归率以及与原始癌症诊断相匹配的非HCT癌症人群的转归率进行比较；2)检查hct前和hct相关暴露与我们感兴趣的结果的关系。该研究利用了现有的数据集和世界上最大的HCT队列之一，使用基于人群的方法，并规避了生存和反应偏差，这些偏差影响了许多依赖于患者自我报告和/或长期随访临床访问的现有HCT研究。还将确定一组受影响的长期幸存者，通过直接医疗记录审查和对潜在可改变的风险因素进行更深入的评估，对结果进行二次验证。该建议结合了HCT研究人员以前未使用的方法和数据来源，包括来自FHCRC的数据来源，并有可能大大扩展对这一高危癌症人群中发生的整个健康结果范围的理解。总的来说，这些结果可能最终影响hct后筛查指南，包括风险预测算法的设计，以确定那些后期不良后果风险增加的人。研究结果还将与经常接受类似治疗暴露的更多癌症患者直接相关。

DESCRIPTION (provided by applicant): With the increasing use of hematopoietic cell transplantation (HCT) and the corresponding increase in the number of long-term survivors, there is an important need to better characterize causes of late morbidity and mortality in this population beyond description of primary disease relapse and graft vs. host disease (GVHD). Using available population-based hospital discharge and death registry data, our existing work has elucidated the magnitude of serious cardiovascular disease among long-term (e2-yr) transplant survivors and is leading to a better understanding of associated pre-HCT and HCT-related risk factors. We now propose to extend this methodology to comprehensively examine all other important health outcomes in this population of e2-yr HCT survivors who are Washington State (WA) residents and treated at the Fred Hutchinson Cancer Research Center (FHCRC) from 1985-2011 (n=2096, 53% allogeneic). In particular, we will focus on serious late pulmonary and infectious complications and 2nd cancers, which along with cardiovascular disease have been identified as leading causes of non-relapse related mortality in prior studies. Pre-HCT and HCT-related exposures from this cohort will be linked to state hospital discharge, death, and cancer registries from the concurrent time period. This will allow us to: 1) compare outcome rates in HCT survivors with those derived from the general population as well as a non-HCT cancer population matched on original cancer diagnosis; 2) examine the association of both pre-HCT and HCT-related exposures with our outcomes of interest. The proposed study takes advantage of existing datasets and one of the world's largest HCT cohorts, uses population-based methods, and circumvents survival and response biases that have affected many existing HCT studies dependent on patient self-report and/or long-term follow-up clinic visits. A cohort of affected long- term survivors also will be identified for whom secondary validation of outcomes via direct medical record review and more in-depth assessment of potential modifiable risk factors can occur. This proposal incorporates methodology and combines data sources not previously used by HCT researchers, including those from FHCRC, and has potential to greatly extend the understanding of the entire spectrum of health outcomes that occur in this at-risk cancer population. Overall, these results may then ultimately influence post-HCT screening guidelines, including the design of risk prediction algorithms to identify those who will be at increased risk for late adverse outcomes. Findings also will be directly relevant to the larger population of cancer patients who often receive similar treatment exposures.