The goal of our studies is to improve disease-free and overall survival in subsets of patients with malignant lymphoma and Hodgkin's disease through the use of high dose therapy and stem cell grafting. The clinical studies proposed for years 04-08 will test 1) the relative efficacy and toxicity of high dose etoposide-containing preparative regimens in poor risk Hodgkin's disease, 2) the curative potential of high dose etoposide preparative regimens in recurrent intermediate and high grade lymphoma and the ability of post-transplant active immunotherapy to further decrease the rate of lymphoma relapse as assessed in a prospective randomized trial, and 3) the ability of consolidative high dose radiochemotherapy to prolong remission duration in advanced stage low grade lymphoma. In order to confirm the validity of our results in the phase II studies, we will employ a case- control statistical analysis in which therapeutic outcome will be compared to individually matched clusters of historical controls obtained from the Stanford Lymphoma Databank. Our studies incorporate novel methods to approach the problem of post- transplant relapse, which is the greatest obstacle to the successful use of ablative therapy and stem cell transplant in malignant lymphomas. Idiotype vaccination, which has been developed and studied by investigators in this Program Project, will be employed in a minimal disease state post- transplant in B-cell lymphoma patients. A novel method of fractionation of allogeneic bone marrow which results in a graft-versus-lymphoma effect, without graft-versus-host disease, has been developed by investigators in Project IV, and this approach will be studied in a clinical trial during the years 05-08. A clinical trial using highly purified stem cell preparations obtained through positive stem cell selection represents an approach to reduce relapse related to contamination of the marrow graft (see: Project IV). In addition, we will evaluate methods of detection of minimal residual disease, developed by investigators in the Program Project (see: Project III).
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