28. Chronic myeloid leukemia. Diagnostics, clinical picture and treatment

Page created on April 14, 2022. Not updated since.

Introduction and epidemiology

Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm characterised by proliferation of the granulocyte lineage. It’s also characterised by the BCR-ABL1 translocation, also known as the Philadelphia chromosome.

It’s mostly a disorder of the elderly, and the incidence is rising. The prognosis has improved significantly following the introduction of BCR-ABL1 inhibitor drugs.

Clinical features

Untreated, the natural history of CML follows three phases:

  • Chronic phase
  • Accelerated phase
  • Blast phase

The chronic phase is indolent and lasts for many years. In this phase, the proliferation is confined to the haematopoietic tissues blood, bone marrow, and spleen. Nowadays, CML is often discovered incidentally in the chronic phase due to unexplained leukocytosis or splenomegaly. Other symptoms include bleeding due to platelet dysfunction, abdominal pain due to splenomegaly, or non-specific symptoms like fatigue, weight loss, and anorexia.

In the accelerated phase, proliferation of myeloid cells increases, worsening the aforementioned symptoms. Splenomegaly can become extreme.

In the blast phase the disease behaves as acute leukaemia, with blasts infiltrating extramedullary tissues, including lymph nodes, skin, and soft tissues. Bone marrow failure develops rapidly.

Diagnosis and evaluation

Labs show:

  • Increased WBCs – can be up to 1000 G/L depending on the phase
    • Basophilia and eosinophilia are common
  • Decreased RBCs and haemoglobin
  • Mildly decreased or increased thrombocytes

Blood smear shows neutrophils in different stages of maturation, but without dysplasia. Bone marrow biopsy shows a hypercellular bone marrow with granulocytic proliferation and decreased erythroid proliferation. Blasts accounts for <5% of BM cells. If >10% it indicates disease progression to accelerated or blast phase.

Genetic testing for the t(9;22) BCR-ABL1 fusion gene confirms the diagnosis.


Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment in the chronic phase. The prototype was imatinib, but nowadays there are second and third generation TKIs as well. Patients must be followed up regularly to monitor for developing drug resistance. In most cases, these drugs must be taken for life to prevent progression to advanced phases, but in some cases it’s possible to achieve treatment-free remission (TFR), where the BCR-ABL1 gene is no longer detectable, and the patient likely no longer requires treatment.

In the accelerated or blast phases, chemotherapy, sometimes followed by allogenic haematopoietic stem cell transplant, is indicated.

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