DESCRIPTION: (Applicant's Abstract) 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.
No Sub Projects information available for 5R21CA069139-02
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