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.

Public Health Relevance

Given the increased use of hematopoietic cell transplantation (HCT) to cure a variety of diseases, there is a growing need to better understand the spectrum of health outcomes experienced by people following HCT compared with other cancer survivors and the general population. Results of this research will help identify risk factors which will hel clinicians better identify and screen HCT survivors at increased risk of subsequent adverse late effects.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Research Grants (R03)
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Special Emphasis Panel (ZCA1)
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Shelburne, Nonniekaye F
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Fred Hutchinson Cancer Research Center
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Leger, Kasey J; Baker, K Scott; Cushing-Haugen, Kara L et al. (2018) Lifestyle factors and subsequent ischemic heart disease risk after hematopoietic cell transplantation. Cancer 124:1507-1515
Chow, Eric J; Antal, Zoltan; Constine, Louis S et al. (2018) New Agents, Emerging Late Effects, and the Development of Precision Survivorship. J Clin Oncol 36:2231-2240
Chow, Eric J; Cushing-Haugen, Kara L; Cheng, Guang-Shing et al. (2017) Morbidity and Mortality Differences Between Hematopoietic Cell Transplantation Survivors and Other Cancer Survivors. J Clin Oncol 35:306-313
Leger, Kasey J; Cushing-Haugen, Kara; Hansen, John A et al. (2016) Clinical and Genetic Determinants of Cardiomyopathy Risk among Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant 22:1094-1101
Chow, Eric J; Wong, Kenneth; Lee, Stephanie J et al. (2014) Late cardiovascular complications after hematopoietic cell transplantation. Biol Blood Marrow Transplant 20:794-800