Monoclonal Antibodies for the Treatment of Leukemia

Ball, Edward

Abstract

The applicant has generated numerous monoclonal antibodies against myeloid antigens and has employed them in the treatment of acute myeloid leukemia (AML). This renewal application seeks to extend the promising results achieved with monoclonal antibody purging of autologous bone marrow. The applicant has shown that monoclonal antibody-purged autologous marrow transplantation can be safely performed and yield long term disease free survival in approximately 50% of patients with AML in second or third complete remission. The applicant now proposes to show more conclusively the contribution of marrow purging to disease free survival by performing a multicenter randomized study comparing autologous transplantation with purged versus unpurged marrow in patients with AML in second remission. Patients will be uniformly treated with a preparative of busulfan and cyclophosphamide and will then be transplanted with either unpurged or antibody-purged marrow. Both groups will be supported with granulocyte- monocyte colony stimulating factor to accelerate engraftment. A total of 11 marrow transplant centers in various geographic regions of the United States will participate in this study.
The second Aim of the application is to determine the significance of prognostic markers in the context of autologous transplantation for AML.
The third Aim i s to develop purging techniques suitable for peripheral blood progenitor cell populations using positive selection of CD34-positive cells followed by a depletion step with an anti-CD15-specific monoclonal antibody.