Chronic myelogenous leukemia (CML) is a fatal neoplastic disease of the blood. Current therapy affords cures only to the small minority of patients who receive an allogeneic bone marrow transplant. The applicant and others showed that the alkaloid drug derived from the Pacific Yew tree in the Fujian province of China, Homoharringtonine (HHT), is effective in both the in vitro and in vivo suppression of the growth of CML cells. Furthermore, the applicant showed that HHT is synergistic with the nucleoside analogue, cytosine arabinoside (cytarabine) in suppressing the CML CFU-GM growth in vitro. A clinical protocol has been approved by the NIH, CTEP/NCI and Institutional Review Boards at the Dana-Farber Cancer Institute, Massachusetts General Hospital and the Brigham and Womens Hospitals in Boston to treat patients with CML with HHT and cytarabine. This application is to provide funds to do the clinical research, gather and analyze the clinical data and to do in vitro correlative studies. These studies include pharmacologic measurement of HTT and cytarabine serum levels during the drug infusions. Additionally, in vitro studies of the pluripotent hematologic stem cell in CML are proposed. This includes identification of the stem cell based on a newly described method of isolation. Preliminary studies are proposed to examine the feasibility of using this method to isolate normal stem cells for use in subsequent clinical protocols.
