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.
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