Kinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival

摘要

Purpose: To assess the kinetics of molecular response to Imatinib Mesylate (IM) therapy in predictingprogression free survival (PFS), sustained hematological, and cytogenetic responses in CPCML. Methods:Ninety five newly diagnosed CPCML Egyptian patients were treated with IM 400 mg daily dose. Cytogeneticanalysis was performed at diagnosis and every 6 months. Molecular monitoring by RT-QPCR was performedat diagnosis and every 3 months during a median follow-up period ( FUp) of 26 months. Mutation detection ofABL domain was performed by ASO-PCR. Results: Hematological response was 98% after three months ofIM therapy. Out of 95 patients 59 showed 2 log reduction of BCR-ABL/ABL ratio after 6 months of whom 49(83%) had complete cytogenetic response (CCyR) and 42 (71%) had major molecular response (MMR) at 12months. BCR-ABL transcripts remained undetectable in 22 patients (39%) at 26 months. Among the remain-ing 34 patients not achieving 2 log reduction at 6 months only 5 (15%) had CCyR and MMR by 12 months.ABL domain mutations were detected in 11/15 (73%) resistant and suboptimal responding patients. Achieving2 log reduction after 6 months of IM therapy significantly correlated with sustained cytogenetic and molecularresponses (p<0.0001), with PFS at 2 years (p<0.03) and inversely with ABL gene mutations (p<0.001). Discus-sion: These data demonstrated the predictive value of early molecular response to IM in CPCML regardingdisease course and PFS. A 2 log reduction at 6 months of IM treatment could be a cut off level predicting resis-tance , CCyR, or suggesting IM dose modification. (Int J Biomed Sci 2009; 5(3):223-228)