Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for many hematologic diseases, but development of serious immune mediated disorders after transplantation limits greater success. Although some immune mediated disorders are very rare (<1%), others such as acute and chronic grafl-versus-host disease (GVHD) are more common (30-50%) and cause high morbidity and mortality. Project 1 is a longitudinal study with the aim of better characterizing the incidence, characteristics, and outcomes of these disorders. We particularly focus on three syndromes with high morbidity and mortality: cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS) and persistent, recurrent or late-onset acute GVHD (late acute GVHD). These syndromes have distinct clinical characteristics and respond poorly to currently available therapies. Based on our current knowledge about potential pathophysiology and response to treatments, we propose biomarker studies and clinical trials of targeted agents elsewhere in the grant proposal. Project 1 will enroll approximately 1000 patients before allogenic HCT who will be followed for two years to collect detailed data about any immune mediated disorders of interest that arise. In addition, research samples will be obtained to provide longitudinal biologic material on affected cases and samples from controls. We will use a subset of these research samples to validate and extend three biomarker models: the Ferrara model of 4 proteins associated with early acute GVHD, the Schultz model of 4 biomarkers associated with chronic GVHD, and the Weissinger urine proteomic patterns associated with acute and chronic GVHD. Since the criteria for positive and negative samples have been determined, we will be able to select purely informative the models. Project 1 is synergistic but not overlapping with a U01 funded observational trial limited to patients with chronic GVHD (2007-2012)

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Project 1 will collect observational clinical data and serial research specimens to achieve the following aims: 1. Characterize and more completely define the onset and course of key immune mediated disorders that are associated with high morbidity and/or mortality after allogeneic HCT. 2. Validate several biomarker models. This study will improve our understanding of these disorders and lead to better treatments.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1-HOP-Y)
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Fred Hutchinson Cancer Research Center
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Inamoto, Yoshihiro; Martin, Paul J; Storer, Barry E et al. (2014) Association of severity of organ involvement with mortality and recurrent malignancy in patients with chronic graft-versus-host disease. Haematologica 99:1618-23
Inamoto, Yoshihiro; Flowers, Mary E D; Sandmaier, Brenda M et al. (2014) Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood 124:1363-71
El-Jawahri, Areej; Pidala, Joseph; Inamoto, Yoshi et al. (2014) Impact of age on quality of life, functional status, and survival in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant 20:1341-8
Inamoto, Yoshihiro; Pidala, Joseph; Chai, Xiaoyu et al. (2014) Assessment of joint and fascia manifestations in chronic graft-versus-host disease. Arthritis Rheumatol 66:1044-52
Palmer, Jeanne; Williams, Kirsten; Inamoto, Yoshihiro et al. (2014) Pulmonary symptoms measured by the national institutes of health lung score predict overall survival, nonrelapse mortality, and patient-reported outcomes in chronic graft-versus-host disease. Biol Blood Marrow Transplant 20:337-44
Kitko, Carrie L; Levine, John E; Storer, Barry E et al. (2014) Plasma CXCL9 elevations correlate with chronic GVHD diagnosis. Blood 123:786-93
Inamoto, Yoshihiro; Kim, Dennis D; Storer, Barry E et al. (2014) Application of CIBMTR risk score to NIH chronic GVHD at individual centers. Blood 123:453-5
Allen, Jessica L; Tata, Prasanthi V; Fore, Matthew S et al. (2014) Increased BCR responsiveness in B cells from patients with chronic GVHD. Blood 123:2108-15
Duarte, R F; Greinix, H; Rabin, B et al. (2014) Uptake and use of recommendations for the diagnosis, severity scoring and management of chronic GVHD: an international survey of the EBMT-NCI Chronic GVHD Task Force. Bone Marrow Transplant 49:49-54
Inamoto, Y; Jagasia, M; Wood, W A et al. (2014) Investigator feedback about the 2005 NIH diagnostic and scoring criteria for chronic GVHD. Bone Marrow Transplant 49:532-8

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