Long-term follow-up information is vital for the overall quality of the data base of this grant and grant CA 18029. To reduce late complications after marrow transplantation, we plan a randomized health care study of interventive versus routine long- term patient follow-up. We also propose to conduct a controlled study of high-dose intravenous immune globulin to prevent infections, lung disease and chronic graft-versus-host disease (GVHD). We will conduct randomized clinical trials of immunosuppressive therapy of normal and high risk chronic GVHD and evaluate toxicity of chronic corticosteroid, cyclosporine and antibiotic treatment. Careful clinical, immune and infection monitoring and standardized protocols of follow-up, prophylaxis and treatment of late complications will serve as logistic support and a well defined patient data base for laboratory studies of Projects I, II, III and V of this grant. We also propose to investigate the nature of immunologic recovery after marrow grafting. Firstly to test the relationship of histocompatibility of donor and recipient to the development of opportunistic infections, patients will be grouped according to donor status: syngeneic, autologous, allogeneic genotypically HLA-identical sibling, allogeneic phenotypically HLA-identical family member, HLA-haploidentical family member or unrelated donor. Patients in each group will be tested in vivo and in vitro with the neoantigens bacteriophage 174 and keyhole limpet hemocyamin (KLH). If depressed serum antibody responses are seen in HLA-nonidentical recipients, we will explore these mechanisms with in vitro cocultures to determine if the deficiency results from failure of helper T cells to cooperate with B cells to synthesize antibody or results from activity of suppressor T cells. Secondly, we will explore in HLA-identical recipients development of immunization schedules for the adoptive transfer of immunity to neoantigens from immunized donors. Use of neoantigens for donor immunization will tell us whether the recipient can be protected against new organisms to which the recipient has not been exposed before transplant. These studies with neoantigens will complement the study of marrow cells responsible for transfer of tetanus immunity outlined in Project II. Finally, the immunologic monitoring capabilities derived from these studies will permit effective evaluation of future attempts to accelerate immunologic recovery after marrow grafting.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA018221-12
Application #
3938037
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1987
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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