Molecular monitoring in chronic myeloid leukemia: response to tyrosine kinase inhibitors and prognostic implications.

Abstract

The majority of patients with chronic-phase (CP) chronic myeloid leukemia (CML) who are treated with Bcr-Abl tyrosine kinase inhibitors such as imatinib and dasatinib achieve cytogenetic disease remission (ie, Philadelphia chromosome-positive cells undetectable by cytogenetic evaluation). However, more sensitive methods are required for monitoring residual disease (ie, molecular monitoring of BCR-ABL transcript levels). It is generally accepted that molecular responses have prognostic significance. Patients with CP CML who achieve early molecular responses are more likely to achieve durable cytogenetic responses and are less likely to experience disease progression. Rising BCR-ABL transcript levels also indicate loss of response, often as a consequence of developing BCR-ABL mutations. However, some studies have suggested that patients who achieve complete cytogenetic disease remission may not derive an additional prognostic benefit from achieving a major molecular response. Practical issues also exist for molecular monitoring with respect to restricted access and variability in methodologies and data reporting. Although molecular monitoring has a clear role in assessing residual disease and determining the risk of disease progression in patients with CML, the importance of cytogenetic monitoring should not be ignored.