Background:
STI571, a potent and specific inhibitor of the BCR-ABL tyrosine kinase, causes arrest of growth or apoptosis in leukemic cells that express BCR-ABL. We evaluated the therapeutic effects and clinical events after the STI571 treatment in advanced chronic myelogenous leukemia (CML).
Methods:
STI571 was administered orally to 24 patients with CML in accelerated phase (AP) (N=17) or blast crisis (BC) (N=17) with a daily dose of 600㎎. Adverse events were observed, and hemotologic, cytogenetic, and molecular responses were evaluated on 1 month of STI571 treatment.
Results:
Hematologic responses were observed in 20 of 24 patients with higher complete hematologic responses in AP (35.3%) compared to BC(14.3%). Partial cytogenetic responses were observed in 2 cases. Fluorescence in situ hybridization showed significant decrease in the percentage of BCR-ABL positive cells, but all still remained above the upper limit of normal range at the time of analysis. No
significant changes were observed in BCR-ABL transcripts after treatment by reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR. Non-hematologic adverse events after STI571 treatment were minimal, whilst hematologic ones were significant with higher frequency in BC rather than AP.
Conclusion:
STI571 induced rapid and significant hematologic responses in patients with advanced CML and adverse events were tolerable. The fact that no responses were achieved in some of these advanced cases underlies the importance of earlier treatment with STI571 to prolong the survival.

Keywords: Chronic myelogenous leukemia, BCR-ABL, STI571, Sytogenetics, Fluorescence in situ hybridization, Polymerase chain reaction, Real-time quantitative PCR,