This is a continuing study of the canine model of total body irradiation, marrow transplantation, methods of support for animals that have no bone marrow function, and immunological problems after marrow transplantation. The clinical marrow transplant protocols used in Seattle and now being widely used in other medical centers are to a considerable extent based on the results of past research supported by this grant. The major areas of research to be conducted under the renewed grant are as follows: (1) prevention and treatment of graft-versus-host disease as the principal obstacle to a wider application of marrow transplantation to human disease; (2) studies of """"""""supralethal"""""""" fractionated total body irradiation designed to define the toxicity and immunosuppressive properties of fractionated irradiation with the objective of developing regimens that can be used to improve the cure rate of patients with acute leukemia; (3) studies of the problem of resistance to hematopoietic grafts and development of new approaches to overcome such resistance and improve the long-term success rate when donor-recipient pairs are not fully matched at the major histocompatibility complex; (4) studies on the use of monoclonal antibody-radioactive isotope conjugates aimed at delivering irradiation to specific tissue sites without systemic toxicity; this approach will be useful in the development of new conditioning regimens for marrow grafting; and (5) studies of transfer of genetic material to hemopoietic stem cells. (IT)
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