@article {37588, title = {Kinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival.}, journal = {International journal of biomedical science : IJBS}, volume = {5}, year = {2009}, note = {n/a}, month = {2009 Sep}, pages = {223-8}, abstract = {

PURPOSE: To assess the kinetics of molecular response to Imatinib Mesylate (IM) therapy in predicting progression 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. Cytogenetic analysis was performed at diagnosis and every 6 months. Molecular monitoring by RT-QPCR was performed at diagnosis and every 3 months during a median follow-up period (FUp) of 26 months. Mutation detection of ABL domain was performed by ASO-PCR.

RESULTS: Hematological response was 98\% after three months of IM 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 12 months. BCR-ABL transcripts remained undetectable in 22 patients (39\%) at 26 months. Among the remaining 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. Achieving 2 log reduction after 6 months of IM therapy significantly correlated with sustained cytogenetic and molecular responses (p\<0.0001), with PFS at 2 years (p\<0.03) and inversely with ABL gene mutations (p\<0.001).

DISCUSSION: These data demonstrated the predictive value of early molecular response to IM in CPCML regarding disease course and PFS. A 2 log reduction at 6 months of IM treatment could be a cut off level predicting resistance, CCyR, or suggesting IM dose modification.

}, issn = {1550-9702}, doi = {10.1016/j.jnci.2013.05.004}, author = {Hossam K. Mahmoud and El Nahas, Yasser and Abdel Moaty, Mohamad and Abdel Fattah, Raafat and El Emary, Mohamad and El Metnawy, Wafaa} }