Kinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival
Journal Title: International Journal of Biomedical Science (IJBS) - Year 2009, Vol 5, Issue 3
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.
Authors and Affiliations
Mahmoud Hossam , Nahas Yasser, Emary Mohamad, Metnawy Wafaa
Keywords
Related Articles
- EP ID EP83275
- DOI -
- Views 96
- Downloads 0
Relationship between NK Cell Activation and Clinical Response in Rheumatoid Arthritis Treated with Rituximab
Introduction: We investigated the relationship between the anti CD20 therapy and the NK cell phenotype in patients with Rheumatoid Arthritis (RA). Methods: patients with seropositive RA according to the ACR criteria tha...
An investigation on the solid dispersions of chlordiazepoxide
The aim of this study was to prepare solid dispersions of chlordiazepoxide techniques to improve its dissolution rate. To this end, three techniques namely, two solvent methods and co-grinding technique were used. Solid...
Spectrophotometric Determination of Risedronate in Pharmaceutical Formulations via Complex Formation with Cu (II) Ions: Application to Content Uniformity Testing
A simple, sensitive, rapid and accurate spectrophotometric method was developed for the determination of risedronate, a bisphosphonate drug important for the treatment of a variety of bone diseases, in raw material and p...
Retroperitoneal Hemorrhage from Adrenocortical Carcinoma as a Poor Prognostic Factor
In most patients, adrenocortical carcinoma is diagnosed at an advanced stage of the disease. A sudden retroperitoneal hemorrhage may sometimes be the first symptom of the adrenal cancer. We describe four patients with ad...
Free Radicals, Antioxidants in Disease and Health
Free radicals and oxidants play a dual role as both toxic and beneficial compounds, since they can be either harmful or helpful to the body. They are produced either from normal cell metabolisms in situ or from external...