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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-Y (50))
Program Officer
Merritt, William D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Fred Hutchinson Cancer Research Center
United States
Zip Code
Martin, Paul J; Storer, Barry E; Inamoto, Yoshihiro et al. (2017) An endpoint associated with clinical benefit after initial treatment of chronic graft-versus-host disease. Blood 130:360-367
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
Lazaryan, Aleksandr; Weisdorf, Daniel J; DeFor, Todd et al. (2016) Risk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors. Biol Blood Marrow Transplant 22:134-40
Arora, Mukta; Cutler, Corey S; Jagasia, Madan H et al. (2016) Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:449-55
Holtan, Shernan G; Khera, Nandita; Levine, John E et al. (2016) Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors. Blood 128:2350-2358
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

Showing the most recent 10 out of 44 publications