The overall objectives of this application largely remain the same. Namely: 1) To conduct a comprehensive survey of key proliferative parameters of tumor cells in different types of human hematopoietic tumors, to correlate these with cell marker studies and clinical features, and to identify those factors which are associated with therapeutic success or failure; 2) To determine the effects of selected cytotoxic drugs on normal and neoplastic human hematopoietic cells in short-term cultures and in established cultures in order to develop leads for improved therapeutic programs; 3) To purify, isolate and characterize the clonogenic progenitor cells in normal huma blood and marrow and compare their proliferative kinetics with those of clonogenic progenitor cells in chronic myelogenous leukemia (CML) and other hematopoietic tumors; 4) To refine procedures for autologous transplantation for frozen and stored hematopoietic stem cells obtained from the marrow and/or blood of patients with poor prognosis lymphomas and other selected tumors prior to treatment to be used to rescue the patients following aggressive chemotherapy aimed at eradicating the tumor. We are also investigating improved methods for purging marrow of residual tumor cells, using cytotoxic drugs or monoclonal antibodies; 5) To develop improved flow microfluorometric procedures for kinetic analysis and improved mathematical models which more accurately and realistically define the kinetic behavior of normal and tumor cell populations and the interactions between them. It is anticipated that improved understanding of the kinetic behavior of the neoplastic cells in different hematopoietic tumors and of the kinetic perturbations caused by treatment will permit development of more individualized and effective treatment for each specific disease entity. This will require more complete knowledge of the cellular origins of the various tumors, more accurate classification and staging techniques, clearer definition of key prognostic factors, and better appreciation of variability in proliferative behavior and responsiveness to treatment within any given tumor category.
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