Diagnostics

• Clinicians should maintain a high index of suspicion if patients present with the following:

  • Severe leukocytosis on routine laboratory testing

  • Splenomegaly

  • Constitutional symptoms (e.g., malaise, fatigue) with nonspecific signs of bone marrow suppression (e.g., anemia, thrombocytopenia)

• Initial diagnostic workup should include:

  • CBC

  • 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.

• CBC and peripheral blood smear

  • Leukocytosis with midstage progenitor cells (e.g., myelocytes, metamyelocytes) and mature cells (e.g., neutrophils)

  • Thrombocytosis

  • Basophilia and eosinophilia

  • Blast cells in peripheral blood can indicate the transition to AP-CML.

  • Anemia

• 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 [3][4]

  • Flow cytometry: can be used to assess the type and maturity of leukocytes in order to detect progression to advanced phases of CML

• 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

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

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.

• Accelerated phase

  • Significantly increased proportion of blast cells

  • Additional genetic mutations are often present.

• Blast phase

  • 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

Identification of the BCR-ABL1 fusion gene is the hallmark of CML and confirms the diagnosis.