Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (349 page)

   
Uric acid
: elevated

Accelerated Phase

   Progression to accelerated phase (or blast crisis) requires the acquisition of other chromosomal or molecular changes.

The most common chromosomal abnormalities are trisomy 8, trisomy 19, an additional copy of the Ph chromosome, and isochromosome 17q.

   For diagnosis, 10–19% blasts of peripheral blood cells or nucleated bone marrow cells are required.

   ≥20% peripheral blood basophiles

   Persistent thrombocytopenia (<100,000/μL) unrelated to therapy

   Increasing spleen size and increasing WBC count unresponsive to therapy Blast Crisis

   ≥20% blasts of peripheral blood cells or of nucleated bone marrow cells.

   Extramedullary blast proliferation

   Large foci or clusters of blasts in the bone marrow biopsy

   Some patients present with Ph-positive acute leukemia; Some of these patients represent CML presenting in blast crisis, whereas others have de novo acute leukemia.

   Laboratory Criteria for Monitoring Response in Treated Patients

   Disease monitoring is one of the key management strategies of CML to assess the response to therapy and to detect early relapse. The most sensitive approach to detect CML is the quantitative real-time PCR (RT-PCR) of the BCR-ABL messenger RNA. By this methodology, one CML cell can be detected in 100,000 to 1 million cells. Another advantage of this methodology is the use of peripheral blood rather than bone marrow tissue. In cases of complete cytogenetic response, present guidelines suggest molecular testing starting 3 months.

   In patients treated with tyrosine kinase inhibitors, monitoring for new mutation in ABL is recommended, because such mutations predict the development of resistance to therapy. Certain mutations, such as those harboring BCR-ABL T315I, are resistant to therapy (a new tyrosine kinase inhibitor is presently being investigated for its effectiveness in patients with this mutation).