In this proposal we have once again emphasized the biology of human leukemia and lymphoma cells and have detailed the accomplishments which have taken place during the course of the second year of this project. The integration of basic studies involving the characterization of hematopoietic stem cells and hematopoietic cells by immunologic, cytologic, and cell culture techniques has already had an impact on our clinical treatment programs. In the next year, we will pursue the development of cell surface and molecular probes for the characterization of the early T cell malignancies utilizing our understanding of T cell receptor gene rearrangements. In addition, we will pursue studies directed at the identification of normal myeloid stem cells and their leukemic clonogenic counterparts utilizing immunologic, cytogenetic and molecular probes. Monoclonal antibodies have proved to be extraordinarily important for diagnosis and increasing evidence will be obtained to support the notion that prognostically important groups can be defined for both B cell and myeloid leukemias. Autologous bone marrow transplant program with J2 and J5 will be continued since the data to date indicates that this approach compares favorably to that obtained in the allogeneic matched system. Studies with the B1 protocol indicate it to be a major new therapeutic modality in previously unresponsive non-Hodgkins's lymphomas. Anti-B-lym peptide antibodies will be utilized for the isolation and characterization of B-lym antigens and it is hoped that these new classes of reagents will complement existing antibodies for the characterization of leukemias. Drs. Kufe, Faller and Frei have demonstrated new pharmacologic approaches which can optimize the treatment of AML, ALL and other tumors. These investigations will continue to exploit combination chemotherapy for the cytoirradication of residual tumor in autologous transplants, asparaginase treatment for ALL and low dose ara-C. Progress made by Drs. Sallan, Weinstein and Mayer in the treatment of ALL and AML utilizing chemotherapy and immunotherapy lend hope to the view that the majority of these diseases will be ultimately curable. The present program has led to multiple interactions of individuals with interests in immunology, molecular biology, cell surface antigens, pharmacology, hematology and oncology. We believe that this integrated approach to cancer treatment and diagnosis has already resulted in a greater understanding of the malignant cell and its control.
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