Describe the diagnostic approach.
Clinicians should maintain a high index of suspicion if patients present with the following:
Severe leukocytosis on routine laboratory testing
Constitutional symptoms (e.g., malaise, fatigue) with nonspecific signs of bone marrow suppression (e.g., anemia, thrombocytopenia)
Initial diagnostic workup should include:
Peripheral blood smear
Bone marrow aspiration and biopsy
Diagnostic confirmation: identification of the Philadelphia chromosome and/or the BCR-ABL1 fusion gene.
Evaluate patients without the Philadelphia chromosome or the BCR-ABL1 fusion gene for other myeloproliferative disorders.
Describe the initial evaluation using CPC, peripheral blood smear and other laboratory studies.
CBC and peripheral blood smear
Leukocytosis with midstage progenitor cells (e.g., myelocytes, metamyelocytes) and mature cells (e.g., neutrophils)
Basophilia and eosinophilia
Blast cells in peripheral blood can indicate the transition to AP-CML.
Further laboratory studies
Leukocyte alkaline phosphatase (LAP): Low LAP is a typical finding and can help distinguish CML from other types of leukemia and leukemoid reactions 
Flow cytometry: can be used to assess the type and maturity of leukocytes in order to detect progression to advanced phases of CML
When are bone marrow aspirations and biopsies indicated?
Bone marrow aspiration and biopsies
Indications: all patients with suspected CML
Supportive findings: hyperplastic myelopoiesis (predominantly granulocytosis) with elevated granulocytic precursor cells, especially myelocytes and promyelocytes
Describe the diagnostic confirmation.
Diagnostic confirmation relies on the detection of the Philadelphia chromosome and/or the BCR-ABL1 gene or its transcripts in the bone marrow or peripheral blood. These tests are usually repeated to assess response to treatment.
Cytogenetic testing: used to confirm the presence of the BCR-ABL1 fusion gene and/or the Philadelphia chromosome, and identify additional genetic mutations
Conventional karyotyping: for confirmation of the Philadelphia chromosome, which contains the BCR-ABL1 fusion gene
FISH analysis: for confirmation of the BCR-ABL1 fusion gene
Molecular testing: quantitative RT-PCR
Describe the definitions of CML phases.
AP-CML and BP-CML have characteristic laboratory parameter values (e.g., the proportion of blast cells in peripheral blood or bone marrow). Some definitions also include further genetic mutations and responsiveness to treatment.
Significantly increased proportion of blast cells
Additional genetic mutations are often present.
Higher proportion of blast cells compared with AP-CML
Extramedullary blast proliferation
Often resistant to targeted therapy due to the presence of multiple genetic mutations