How should I monitor a patient with CML for treatment response and potential resistance to therapy?

Monitoring a patient with chronic myeloid leukemia (CML) for treatment response and potential resistance involves regular assessment of molecular and cytogenetic markers to guide therapy adjustments. Initial monitoring should include quantitative measurement of BCR-ABL1 transcript levels using real-time PCR at defined intervals, typically every 3 months during the first year of treatment, to evaluate molecular response and detect early signs of resistance ¹. Cytogenetic analysis of bone marrow cells complements molecular testing by assessing the proportion of Philadelphia chromosome-positive metaphases, especially if molecular results are ambiguous or if there is clinical suspicion of resistance ¹.

Failure to achieve specific molecular milestones, such as a major molecular response (MMR) by 12 months, or a rising BCR-ABL1 transcript level after an initial response, should prompt consideration of treatment resistance and further investigation ¹. In such cases, mutation analysis of the BCR-ABL1 kinase domain is recommended to identify mutations conferring resistance to tyrosine kinase inhibitors (TKIs) like imatinib (Linke and Dempke, 2007). This molecular resistance testing serves as an early indicator for treatment change, allowing timely switch to second- or third-generation TKIs tailored to the mutation profile (Fava et al., 2012).

Regular clinical assessment and blood counts remain essential to monitor hematologic response and detect adverse effects, but molecular monitoring is the cornerstone for detecting resistance before clinical relapse occurs ¹. The integration of guideline-recommended monitoring intervals with mutation analysis informed by emerging molecular resistance patterns optimizes patient outcomes by enabling early intervention (Linke and Dempke, 2007; Fava et al., 2012).