Harringtonine and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

Harringtonine (HT) and homoharringtonine (HHT) are Cephalotaxus alkaloids with considerable antileukaemic activity. The objectives of this research were to (1) determine the content of HT and HHT present in Cephalotaxus griffithii needles alkaloid fraction (CGAF) and (2) compare the antiproliferative activity of CGAF, with that of HT and HHT on chronic myelogenous leukaemia K562 cell. The concentration of HT and HHT was found to be 122.14 and 16.79 mg/g of CGAF, respectively. Treatment of K562 cells with CGAF, HT and HHT decreased the viable cells in a dose- and time-dependent manner. Interestingly, the maximum cell death was found in CGAF, with IC50 value which was 3- to 4.6-fold lower than those of HT and HHT. Our results indicate that HT content in the needles of C. griffithii is higher than HHT, and alkaloids other than HT and HHT in CGAF are predominantly responsible for K562 cell death.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Apoptosis; Cephalotaxus; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Harringtonines; Homoharringtonine; Humans; Inhibitory Concentration 50; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

To quantitatively evaluate the impact of Sokal's risk index and that of 2 therapy protocols on the clinical outcome of patients with chronic myeloid leukemia (CML).. With the assistance of Access 2000 database of CML, 94 patients with CML were grouped on the basis of either different therapy protocols utilizing harringtonine plus Ara-C (HA) vs hydroxyurea (Hu) or Sokal scores, and the impact of therapy protocol and risk profile were quantitatively evaluated respectively.. Treatment protocol utilizing HA was incapable of lengthening the duration of chronic phase (DCP) of CML, regardless of its better short-term effect than that of Hu. The impact of risk profile of the patients on clinical remission rate and DCP was more significant than that of the therapy protocols.. HA should not be used as the first-line protocol in the treatment of CML patients in chronic phase who have not received any previous medical intervention. Patients should be categorized according to the risk profile for choosing appropriate treatment protocol and making better clinical judgement.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Female; Harringtonines; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Outcome Assessment, Health Care; Treatment Outcome