In a patient suffering from chronic myelogenous leukemia, what indicates therapeutic failure due to drug resistance?

In the context of chronic myelogenous leukemia (CML) treatment, undetectable drug levels in leukemic cells indicate that the therapeutic agent, often a tyrosine kinase inhibitor like imatinib, is not reaching the leukemic cells effectively or that the cells have developed resistance to the drug. This resistance can be due to various mechanisms, such as mutations in the BCR-ABL gene (the gene responsible for the Philadelphia chromosome present in most CML cases), which can alter the target protein and diminish the drug's effectiveness.

Achieving therapeutic drug levels is crucial for the effectiveness of treatment in CML, so undetectable levels suggest that the therapy is not working as intended, prompting the need for potential therapeutic adjustments.

High leukocyte counts and elevated platelet counts can indicate a persistent disease due to inadequate treatment response but do not directly measure the presence or absence of the drug at the cellular level. The presence of the Philadelphia chromosome is a hallmark of CML and does not indicate therapeutic failure; rather, it is a key marker used for diagnosis and monitoring the disease. Thus, the indication of poor drug levels within the leukemic cells is a clearer and more direct marker of drug resistance and therapeutic failure.