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Updated: Dec 27 2021

Chronic Myeloid Leukemia (CML)

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  • Snapshot
    • A 67-year-old woman presents for her annual check-up. She feels great and denies any symptoms. Her physical exam is completely normal. Her routine blood tests come back with marked leukocytosis with increased neutrophils. Leukocyte alkaline phosphatase is low. Her physician is suspicious for a heme malignancy.
  • Introduction
    • Also known as chronic myelogenous leukemia
    • Clonal hematopoietic stem cell disorder
    • Clinical course
      • chronic phase (most present in this phase)
        • some patients may be completely asymptomatic
        • incident finding on CBC
      • accelerated phase
      • blast phase
      • may transform into AML or ALL (“blast crisis”)
  • Epidemiology
    • Demographics
      • median disease onset 50 years of age in clinical trials to 60 years of age in cancer registry data
      • slightly male > female
      • Typically in older patients
    • 15% of all adult leukemias
    • Risk factors
      • radiation from nuclear radiation
      • radiation from radiography (radiologists may be at risk)
      • radiation from cellular phone NOT a risk factor
  • ETIOLOGY
    • Pathogenesis
      • Philadelphia chromosome
      • translocation t(9;22)
      • BCR-ABL fusion gene
        • hyperactive tyrosine kinase
  • Presentation
    • Chronic phase
      • fatigue
      • night sweats
      • malaise
      • weight loss
      • fever
      • splenomegaly
        • LUQ discomfort
        • early satiety
      • pruritus after hot bath/showers
    • Accelerated or blast phase
      • bony pain
      • lymphadenopathy
      • variable skin findings
      • extramedullary mass
      • rapidly enlarging spleen
  • studies
    • Complete blood count with differential
      • WBC
      • ↑ neutrophils
      • ↑ basophils
      • immature granulocytes (metamyelocytes, myelocytes, and promyelocytes)
    • ↓ leukocyte alkaline phosphatase
      • low activity in mature granulocytes
    • Bone marrow aspirate and biopsy
      • ↑ cellularity
      • immature granulocytes
      • blasts present in accelerated or blast phase
    • Cytogenetic analysis or FISH showing Philadelphia chromosome (most accurate)
      • bone marrow cells or
      • peripheral blood
  • Differential Diagnosis
    • Chronic myelomonocytic leukemia
    • Chronic eosinophilic leukemia
    • Primary myelofibrosis
    • Acute myeloid leukemic
    • Leukemoid reaction
      • ↑ WBC
      • ↑ leukocyte alkaline phosphatase
  • Treatment
    • Medical management
      • tyrosine kinase inhibitors are first-line
        • imatinib (Gleevec)
        • nilotinib
        • dasatinib, especially for accelerated phase or blast phase
    • Surgical management
      • hematopoietic stem cell transplant
        • never first-line
        • the only curative therapy
  • Complications
    • Transformation to acute leukemia (blast crisis)
      • may cause leukostasis and sludging
        • management
          • IV fluids
          • chemotherapy
          • leukapheresis
    • Infection
    • bleeding
    • Gout
    • Bone pain
    • Splenic infarcts due to splenomegaly
  • Prognosis
    • Worse prognosis with older age at diagnosis
    • Increased overall survival with tyrosine kinase inhibitor therapy
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