The goal of our study is to improve disease-free survival and overall survival in patients with hematologic malignancies through the use of high dose therapy and autologous stem cell grafting. It is the intent to introduce novel approaches designed to increase the efficacy and potential safety of high dose chemotherapy or chemoradiotherapy and stem cell support for patients who are undergoing treatment for refractors B cell lymphoma, Hodgkin's disease and leukemia. These innovations include using high dose sequential chemotherapy for the treatment of relapsed Hodgkin's disease and the use of yttrium labeled monoclonal antibodies to the CD20 antigen as part of the preparatory regimen for patients undergoing autologous bone marrow transplantation (BMT) for B cell lymphoma. We will also study the feasibility, effectiveness and toxicity of adding yttrium labeled monoclonal antibodies to either the CD33 or CD45 antigen in patients undergoing autologous BMT as treatment for acute myelogenous leukemia and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). In addition, in this project we will investigate the use of a nw vector, an adeno-associated virus for efficient transduction of hematopoietic stem cells. This approach is designed to elucidate the pattern and degree of hematopoietic and immune reconstitution, as well as the potential cause of relapse that occurs after autologous BMT for patients undergoing treatment for low grade lymphoma following radiation and non-radiation containing regimens. We will also study the use of a ribozyme designed to cleave the hybrid RNA that results from the t (9;22) chromosome translocation of Ph+ ALL with the goal to purge peripheral blood stem cells of leukemia in patients undergoing autologous BMT for this disorder. These studies will test novel methods designed to decrease the major problem of relapse, which is the greatest obstacle to successful use of autologous stem cell transplant for treatment of malignant lymphomas, Hodgkin's disease, and acute leukemia. The project focuses on modifying the preparatory regimen to treat the residual body burden of malignancy, a well as developing molecular methods designed to purge the stem cell product of contaminating leukemia cells. Finally, Project 2 will serve as a clinical resource for experimental Projects.
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