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.
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.
|Merkel, Peter A; Manion, Michele; Gopal-Srivastava, Rashmi et al. (2016) The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis 11:66|
|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|
|Kariminia, Amina; Holtan, Shernan G; Ivison, Sabine et al. (2016) Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells. Blood 127:3082-91|
|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|
|Arai, Sally; Pidala, Joseph; Pusic, Iskra et al. (2016) A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. Clin Cancer Res 22:319-27|
|Yu, Jeffrey; Storer, Barry E; Kushekhar, Kushi et al. (2016) Biomarker Panel for Chronic Graft-Versus-Host Disease. J Clin Oncol 34:2583-90|
|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 :|
|Williams, Kirsten M; Cheng, Guang-Shing; Pusic, Iskra et al. (2016) Fluticasone, Azithromycin, and Montelukast Treatment forÂ New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:710-6|
|MÃ¼ller, 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|
Showing the most recent 10 out of 41 publications