Autologous marrow transplantation for non-Hodgkin's lymphoma and Hodgkin's disease has produced extended disease-free survival for some patients but malignant relapse remains the most frequently reported cause of post-transplant treatment failure. In this proposal we will investigate clinical and laboratory initiatives designed to reduce the incidence of malignant relapse after transplantation by the application of immunotherapy. The clinical studies proposed include the continuation of an ongoing randomized trial comparing bone marrow stem cells versus peripheral blood stem cells for hematologic and immunologic reconstitution following transplantation. Because there may be differential contamination of blood versus marrow with clonogenic tumor cells, we will also assess this controlled trial for differences in disease-free survival. We will also conduct a Phase I and follow-up Phase II trial of infusional recombinant human interleukin-1 alpha given during the first 14 days following BMT to promote hematologic and immunologic recovery and provide immunologically based anti-tumor responses. In addition, we propose to conduct a Phase II trial seeking efficacy for recombinant human IL-2 given by continuous infusion during the first three weeks following autologous transplantation, in promoting immunologic activation and antineoplastic activity. In related, developmental laboratory studies we propose to explore: the use of the cytokines IL-1 alpha and IL-2 to define their antineoplastic effectiveness against human and murine lymphoma cell lines; to explore their utility in generating effector cells capable of killing these lymphoma targets in vitro; to generate effectors capable of adhering to extracellular matrix proteins and homing towards tumor sites in vivo; and finally, to explore the use of these cytokines' and cytotoxic effector cells' ability to improve survival in vivo in severe combined immunodeficiency (SCID) mice with human lymphomas and normal mice with lymphoma undergoing syngeneic BMT. These laboratory studies are designed to allow us to develop new clinical strategies for more effective immunotherapy accompanying autologous marrow transplantation in order to prevent malignant relapse and improve overall patient survival.
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