Autologous marrow transplantation has been widely used in the treatment of acute myeloid leukemia (AML). To reduce the incidence of relapse, a variety of purging methods have been developed to remove leukemic cells that may be present in the marrow, including the use of 4- hydroperoxycyclophosphamide (4-HC) a derivative of cyclophosphamide. Although the therapeutic efficacy of marrow purging has yet to be firmly established, most purging methods eliminate hematopoietic colony forming cells and thus may contribute to the delayed engraftment seen in these patients. As an approach to obtaining rapid engraftment with 4-HC purged marrow, we propose to utilize methods we have developed to generate colony forming cells (CFC) from their precursors. We will determine if these methods can be applied to generate substantial numbers of CFC from purged marrow that may be infused in vivo to provide a rapid initial wave of engraftment. Our approach is based on our observation that CFC can be generated from CD33- precursors by culture in the presence of marrow stroma or human stem cell factor (SCF) combined with IL-3 and G-CSF; and that these precursors are predominantly or completely normal as opposed to malignant in patients with AML.
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