Abstract

This is a continuing study in the canine model of total body irradiation, marrow transplantation, methods of support for animals that have no bone marrow function and immunologic problems after marrow transplantation. The major areas of proposed research to be conducted under the renewed grant are as follows: I. Study the problem of resistance to hematopoietic grafts, conduct studies designed to overcome such resistance and improve the long-term success rate when donor-recepient pairs are not fully matched for the major histocompatibility complex. II. Study monoclonal antibody-radioactive isotope conjugates for their usefulness in conditioning dogs for marrow transplantation. III. Study high-dose total body irradiation and compare toxicities and immuno supperssive properties of fractionated versus single dose irradiation at different dose rates. The objective is to develop conditioning regimens for histoincompatible marrow transplant recipients and those with malignancies. IV. Prevention and treatment of graft-versus-host disease which is recognized as the principle obstacle to a wider application of marrow transplantation to the treatment of human diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031787-09
Application #
3169895
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1981-05-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Wagner, J L; Burnett, R C; Storb, R (1999) Organization of the canine major histocompatibility complex: current perspectives. J Hered 90:35-8
Yamaguchi, M; McSweeney, P A; Kimball, L et al. (1999) Recognition of major histocompatibility complex class II antigens by two anti-HLA-DR monoclonal antibodies on canine marrow cells correlates with effects on in vitro and in vivo hematopoiesis. Transplantation 68:1161-71
Huss, R; Theis, S; Deeg, H J (1999) CDK-inhibitor independent cell cycle progression in an experimental haematopoietic stem cell leukaemia despite unaltered Rb-phosphorylation. Br J Cancer 81:808-13
Graumann, M B; DeRose, S A; Ostrander, E A et al. (1998) Polymorphism analysis of four canine MHC class I genes. Tissue Antigens 51:374-81
Storb, R; Raff, R; Deeg, H J et al. (1998) Dose rate-dependent sparing of the gastrointestinal tract by fractionated total body irradiation in dogs given marrow autografts. Int J Radiat Oncol Biol Phys 40:961-6
Sandmaier, B M; Storb, R; Bennett, K L et al. (1998) Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model. Blood 91:3494-502
Yu, C; Seidel, K; Nash, R A et al. (1998) Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts. Blood 91:2581-7
Krizanac-Bengez, L; Moore, P F; Barsoukov, A et al. (1998) The expression and differentiation pattern of cell antigens and adhesion molecules on the nonadherent cell population in canine long-term marrow culture: a biphasic development of myeloid and lymphoid cells. Tissue Antigens 51:141-55
Storb, R; Yu, C; Wagner, J L et al. (1997) Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 89:3048-54
Deeg, H J; Seidel, K; Hong, D S et al. (1997) In vivo radioprotective effect of AcSDKP on canine myelopoiesis. Ann Hematol 74:117-22

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