Considerable progress has been made to remedy transplant-related complications in patients receiving HLA-identical sibling donor marrow. While many stem cell grafts continue to be from this donor source, a greater proportion of transplants is being carried out with stem cells from alternative donors, including less well-matched family members and unrelated individuals. As a result, the spectrum of transplant-related complications has changed. These changes include an increased incidence and severity of graft-versus-host disease (GVHD), an increase in infectious complications, and an increased incidence of graft failure. The current grant proposes studies to define mechanisms responsible for these complications so that effective therapies can be developed. long- term follow-up-prevention and treatment of chronic GVHD, and infection prophylaxis will be addressed the first project. The second project will define the immunological function of novel MHC class 1 molecules (MICA and MICB) that are polymorphic and almost exclusively expressed in gut epithelium, and test the hypothesis that these molecules play important roles in the development of intestinal GVHD. The third project will address the problem of graft failure by testing the hypothesis that GVH reactions and cytomegalovirus infection compromise marrow function. A core on information management and statistical support complete the Program Project Grant.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA018221-23
Application #
2683400
Study Section
Special Emphasis Panel (ZCA1-RRS-8 (M1))
Program Officer
Wu, Roy S
Project Start
1978-09-01
Project End
2002-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
23
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Mielcarek, Marco; Storer, Barry E; Boeckh, Michael et al. (2009) Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes. Blood 113:2888-94
Tseng, Li-Hui; Storer, Barry; Petersdorf, Effie et al. (2009) IL10 and IL10 receptor gene variation and outcomes after unrelated and related hematopoietic cell transplantation. Transplantation 87:704-10
Bensinger, W I (2009) Role of autologous and allogeneic stem cell transplantation in myeloma. Leukemia 23:442-8
Bensinger, William (2008) Stem-cell transplantation for multiple myeloma in the era of novel drugs. J Clin Oncol 26:480-92
Storek, Jan (2008) Immunological reconstitution after hematopoietic cell transplantation - its relation to the contents of the graft. Expert Opin Biol Ther 8:583-97
Bensinger, William I (2007) Is there still a role for allogeneic stem-cell transplantation in multiple myeloma? Best Pract Res Clin Haematol 20:783-95
Carpenter, Paul A; Hoffmeister, Paul; Chesnut 3rd, Charles H et al. (2007) Bisphosphonate therapy for reduced bone mineral density in children with chronic graft-versus-host disease. Biol Blood Marrow Transplant 13:683-90
Bensinger, William I (2007) Reduced intensity allogeneic stem cell transplantation in multiple myeloma. Front Biosci 12:4384-92
Bensinger, W I (2006) The current status of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma. Leukemia 20:1683-9
Zaucha, Renata E; Buckner, Dean C; Barnett, Todd et al. (2006) Modified total body irradiation as a planned second high-dose therapy with stem cell infusion for patients with bone-based malignancies. Int J Radiat Oncol Biol Phys 64:227-34

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