It is the objective of our studies to improve the results of treatment with high dose therapy and autografting in Hodgkin's disease and the non-Hodgkin's lymphomas. We intend to accomplish this goal through the study of novel preparatory regimens and post-transplant immunotherapy. Complementary pathology studies are planned to better define biologic correlates of the clinical results. The proposed clinical studies build on our previous research in these diseases. A new preparatory regimen (CCNU, VP16, cyclophosphamide) developed at Stanford University will be evaluated in patients with low risk Hodgkin's disease. Multiple cycle high dose therapy has been developed to reduce relapse in high risk Hodgkin's disease patients. We will compare the efficacy and toxicity of high dose sequential chemotherapy with our standard preparatory regimen in a Phase III trial in non-Hodgkin's lymphoma. Correlations will be made with a number of biologic parameters assessed in lymphoma tissues in order to further elucidate factors that may predict the treatment outcome after high dose therapy and autografting. All autografted patients will be studied by sensitive molecular and cytogenetic techniques designed to predict genomic instability and the risk for treatment- related myelodysplasia or acute leukemia. In collaboration with investigators in Project III, we will study the feasibility and toxicity of infusing cytokine-induced killer cells into patients with refractory non-Hodgkin's lymphoma. These CIK cells represent a novel therapeutic which, when used as an adjunct to high dose therapy and autografting, may reduce the major problem of relapse after autografting. The studies in Project II are based on past accomplishments in the research laboratory and the clinic. Analysis of previous experience allows us to define risk groups in Hodgkin's disease and structure preparatory regimens accordingly. We plan a comprehensive approach to the study of non-Hodgkin's lymphoma by characterizing lymphoma tissues, purging lymphoma from the apheresis product, comparing two preparatory regimens, and introducing a novel post-transplant immunotherapy to the clinic. The potential for myelodysplasia or acute leukemia as a late effect of high dose therapy will be studied prospectively in all patients. Project II will serve as a clinical resource for other subprojects.
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