title: Kinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology and BMT, Cairo University, Egypt.
authors.forename: Hossam K
authors.initials: HK
authors.lastname: Mahmoud
authors.forename: Yasser
authors.initials: Y
authors.lastname: El Nahas
authors.forename: Mohamad
authors.initials: M
authors.lastname: Abdel Moaty
authors.forename: Raafat
authors.initials: R
authors.lastname: Abdel Fattah
authors.forename: Mohamad
authors.initials: M
authors.lastname: El Emary
authors.forename: Wafaa
authors.initials: W
authors.lastname: El Metnawy
keywords: ABL kinase mutations; CML; cytogenetic responses; imatinib mesylate; molecular responses