The diagnosis of chronic myelogenous leukemia (CML) consists of a complete blood count with differential, peripheral blood smear, and bone marrow analysis. Although typical hepatomegaly and splenomegaly may be imaged by using a liver/spleen scan, these abnormalities are often so obvious clinically that radiologic imaging is not necessary. The biologic basis of the disease is the bcr/abl compund gene and diagnosis of CML is based on the histopathologic findings in the peripheral blood and the Philadelphia (Ph1) chromosome in bone marrow cells or bcr/abl positivity. Treatment with imatinib or other tyrosine kinase inhibitors is predicated on the presence of bcr/abl.
Ph-negative CML patients should be tested for bcr/abl. Many such patients in fact have complex chromosomal abnormalities that mask the (9;22) translocation, or have evidence of the translocation by FISH or RT-PCR in spite of normal routine karyotyping. The small subset of patients without detectable molecular evidence of bcr-abl fusion may be better classified as having an undifferentiated myelodysplastic/myeloproliferative disorder, as their clinical course tends to be different from patients with CML.
Gleevec is not appropriate for bcr/abl negative patients. FDA indicates is specifically for newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase and the same population in blast phase. The drug is not indicated without a presence of the PH chromosome and is appropriate off label if PH chromosome is negative but bcr/abl is identified.
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