This program project grant application seeks support for clinical research projects dealing with bone marrow transplantation for hematologic malignancies. The clinical section focuses on marrow transplantation as a treatment for acute myelogenous and lymphocytic leukemias, acute malignant myelofibrosis and the accelerated phase of chronic granulocytic leukemia. In a study on the molcular aspects of hemoglobin F, features of fetal erythropoiesis after marrow grafting will be investigated. The assessment of antibody formation against transfused platelets and granulocytes, the validity of newly described in vitro compatibility tests and the response to platelet transfusions and granulocyte transfusions will be evaluated. Immunological reconstitution and its relationship to interstitial pneumonia in recipients of allogeneic marrow grafts will be studied using immunologic markers. The biologic significance of cytomegalovirus infection after marrow grafting will be studied by sequential virus cytomegalovirus polypeptides and glycoproteins. Molecular clonging of purified cytomegalovirus polypeptides will be attempted as a means of producing highly purified response to purified isolation, by clinical detection of viral proteins, and by determination of the immune antigen. Another project addresses the problem of prevention and treatment of graft versus host disease by the use of monoclonal antibodies in an animal system. FInally a murine system will be studied as a model for autologens marrow transplantation as a therapy of acute leukemia after in vitro manipulation of the marrow innoculum with drugs, monoclonal antibodies or anti-lymphocyte sera.
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