Recipients of allogeneic hematopoietic cell transplants (HCT) suffer from unique immune mediated disorders. Although components of these disorders resemble known autoimmune syndromes or solid organ allograft rejection, the underlying immunology is poorly characterized. In 2007, approximately 9,500 allogeneic HCTs were performed in the United States, primarily for the treatment of rare diseases such as leukemia, lymphoma, multiple myeloma and other hematologic diseases. Approximately 50% of allogeneic HCT recipients develop immune mediated disorders resulting in high treatment-related morbidity and mortality. The two most common immune mediated complications are heterogeneous syndromes collectively called """"""""acute graft-versus-host disease (GVHD)"""""""" and """"""""chronic GVHD."""""""" Chronic GVHD is the leading cause of non-relapse death more than 2 years after allogeneic HCT. The different syndromes within GVHD are likely to have different pathogenic mechanisms. The goal of this Rare Diseases Clinical Research Consortium (RDCRC) is to advance our understanding and treatment of these disorders. Project 1 is an observational study with integrated biologic investigations. Patients will be enrolled prior to HCT and followed prospectively for the development of immune mediated disorders. Patients who are diagnosed with chronic GVHD will then be intensively studied through the Consortium's currently funded U01 study, """"""""Improving Outcomes Assessment in Chronic GVHD,"""""""" (PI: Stephanie Lee, CA118953-01A1, 2007- 2012). Project 2 and the Pilots propose three clinical trials targeting well-recognized but poorly understood syndromes with particularly high morbidity/mortality: cutaneous sclerosis, bronchiolitis obliterans syndrome and late acute GVHD. Novel targeted therapies and extensive biologic analysis will help us better understand and treat these disorders. Components of the RDCRC also focus on training, education, outreach and interaction with other members of the Rare Diseases Network. We collaborate with three patient advocacy organizations to reach out to patients, families, and physicians.

Public Health Relevance

Immune mediated disorders develop in 50% of allogeneic hematopoietic cell transplant recipients and are major causes of suffering and treatment-related death. We propose a set of well integrated clinical and laboratory studies which will significantly advance our knowledge and lead to better ways to diagnose, prevent, and treat these disorders.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
8U54CA163438-03
Application #
8134958
Study Section
Special Emphasis Panel (ZRG1-HOP-Y (50))
Program Officer
Merritt, William D
Project Start
2009-09-25
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$1,167,500
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Lee, Stephanie J (2017) Classification systems for chronic graft-versus-host disease. Blood 129:30-37
Lee, Stephanie J; Nguyen, Tam D; Onstad, Lynn et al. (2017) Success of Immunosuppressive Treatments in Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant :
Cheng, Guang-Shing; Storer, Barry; Chien, Jason W et al. (2016) Lung Function Trajectory in Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplant. Ann Am Thorac Soc 13:1932-1939
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Müller, J A; Zirafi, O; Roan, N R et al. (2016) Evaluation of EPI-X4 as a urinary peptide biomarker for diagnosis and prognosis of late acute GvHD. Bone Marrow Transplant 51:1137-9
Palmer, Jeanne; Chai, Xiaoyu; Pidala, Joseph et al. (2016) Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease. Blood 127:160-6
Williams, Kirsten M; Cheng, Guang-Shing; Pusic, Iskra et al. (2016) Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:710-716

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