Quantitative Monitoring of BCR / ABL Transcript During STI-571 Therapy

Abstract

PCR for the BCR / ABL fusion transcript provides a highly sensitive and specific method for detecting minimal residual disease in patients with chronic myeloid leukemia (CML). We sought to determine if quantitative PCR measurement of peripheral blood BCR / ABL transcript can be used to monitor response in CML patients with clinically evident disease while receiving the protein tyrosine kinase inhibitor STI-571. Serial bone marrow cytogenetics and peripheral blood BCR / ABL mRNA levels were measured in 17 patients [9 with chronic phase (CP) and 8 with accelerated phase or blast crisis (AP/BC)] during 1 year of treatment. Overall, quantitative PCR BCR / ABL transcript level decreased by a median of 0.9 log during the first 3 months, and by 1.6 logs by 12 months. Among cytogenetic responders (6 CP and 2 AP/BC), median BCR / ABL copy number was 0.9 and 2.1 logs lower than baseline after 3 and 12 months of treatment, respectively. No patient became PCR-negative for BCR / ABL. Among cytogenetic non-responders, BCR / ABL transcript level decreased by 0.4 logs after 3 months, with no subsequent reductions. At study entry, BCR / ABL expression in cytogenetic responders and non-responders was similar. However, BCR / ABL expression became significantly different 3 months after treatment (p =0.02), and increasingly different with continued therapy (p =0.04, 0.005, 0.0008 at 6, 9 and 12 months, respectively). Our results demonstrate that PBMC BCR / ABL mRNA levels correlate well with response to STI-571. This non-invasive, rapid and sensitive PCR-based assay can be used to monitor response to STI-571.

• Chronic Myelocytic Leukemia
• Pcr
• Sti-571
• Quantitative