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For further information, see CMDT Part 13-27: Chronic Myeloid Leukemia

Key Features

Essentials of Diagnosis

  • Elevated white blood count (WBC)

  • Left-shifted myeloid series but low percentage of promyelocytes and blasts

  • Presence of bcr/abl gene (Philadelphia chromosome)

General Considerations

  • Myeloproliferative disorder characterized by overproduction of myeloid cells

  • Associated with characteristic chromosomal abnormality, the Philadelphia chromosome, a reciprocal translocation between long arms of chromosomes 9 and 22

  • Translocated portion of 9q contains abl, a protooncogene, which is received on 22q, at the break point cluster (bcr) site

  • The fusion gene bcr/abl produces Ca novel protein that possesses tyrosine kinase activity, leading to leukemia

  • Disease may progress from chronic phase to accelerated phase and to blast crisis

  • Progression is often associated with added chromosomal defects superimposed on the Philadelphia chromosome

  • Blast crisis chronic myeloid leukemia (CML) is morphologically indistinguishable from acute leukemia

Demographics

  • CML occurs mainly in middle age; median age at presentation is 50 years

Clinical Findings

Symptoms and Signs

  • Fatigue, night sweats, and low-grade fevers

  • Abdominal fullness related to splenomegaly

  • Leukostasis clinical syndrome (blurred vision, respiratory distress, and/or priapism) is rare

  • Sternal tenderness

  • Fever in absence of infection, bone pain, and splenomegaly may mark disease acceleration

Differential Diagnosis

  • Reactive leukocytosis resulting from infection, inflammation, or cancer

  • Other myeloproliferative disorder: essential thrombocytosis, polycythemia vera, or myelofibrosis

Diagnosis

Laboratory Tests

  • Median WBC at diagnosis is 150,000/mcL, although some cases are discovered when WBC is only modestly increased

  • In the rare cases of the leukostasis clinical syndrome, WBC usually > 500,000/mcL

  • Hematocrit is usually normal at presentation

  • Platelet count may be normal or elevated (sometimes strikingly elevated)

  • Basophilia and eosinophilia may be present

  • Peripheral blood smear

    • Myeloid series left-shifted with mature forms dominating

    • Blasts usually < 5%

    • Red blood cell (RBC) morphology normal; nucleated RBCs rarely seen

  • The diagnosis is confirmed by finding the Philadelphia chromosome (bcr/abl gene) in peripheral blood

  • Progressive anemia and thrombocytopenia occur in accelerated and blast phases, and percentage of blasts in blood and bone marrow increases

Diagnostic Procedures

  • Bone marrow aspirate and biopsy: hypercellular, with left-shifted myelopoiesis is not diagnostic, but distinguishes chronic phase from more advanced disease

  • Cytogenetics in bone marrow may show abnormalities in addition to the Philadelphia chromosome

  • When blasts comprise > 20% of bone marrow cells, blast phase of CML is diagnosed

Treatment

Medications

  • Imatinib mesylate, 400 mg orally once daily

    • Results in nearly universal (98%) hematologic control of chronic phase disease

    • Rate of a major molecular response is ∼30% at 1 year

  • Dasatinib and nilotinib

    • Increase the rate of achievement of a major molecular response compared to imatinib

      • 64% for dasatinib ...

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