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. 2009 Sep;5(3):223-8.

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

Hossam K Mahmoud  1 , Yasser El Nahas, Mohamad Abdel Moaty, Raafat Abdel Fattah, Mohamad El Emary, Wafaa El Metnawy
Affiliations

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

Hossam K Mahmoud et al. Int J Biomed Sci. 2009 Sep.

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.

Keywords: ABL kinase mutations; CML; cytogenetic responses; imatinib mesylate; molecular responses.

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Figures

Figure 1
Figure 1
Two log reductions in Bcr-Abl/Abl mRNA ratio at 6 months predicts better PFS at 24 months of IM therapy.
Figure 2
Figure 2
Overall survival of the 95 patients in the study group.
See this image and copyright information in PMC

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