Chronic Myelogenous Leukemia (CML)

What is CML?

Chronic myelogenous leukemia (CML) is one of a group of myeloproliferative disorders. These are disorders that affect the bone marrow, in which excess red blood cells, granulocytes, and/or platelets are produced. It is also referred to as chronic myeloid leukemia, chronic granulocytic leukemia, or chronic myelocytic leukemia.

More than 95% of patients diagnosed with CML have the presence of a cytogenetic anomaly known as the Philadelphia chromosome, a translocation of genes on chromosomes 9 and 22, which causes the Abelson (ABL) oncogene on chromosome 9 to transfer to a site on chromosome 22 known as the breakpoint cluster region (BCR). This ABL/BCR fusion causes the abnormal production of tyrosine kinase protein, which causes the abnormal myelopoiesis of CML (Deininger, Goldman, & Melo, 2000).

CML exists in phases.

  • Chronic phase
  • Accelerated phase
  • Blast phase (also called blast crisis)

What are the initial symptoms of CML?

The typical physical presentation of CML is that of splenomegaly, which may present as minimal to profound. However, in about 10% of patients, splenomegaly is absent at presentation (National Cancer Institute, 2011b). When the symptoms do occur, they tend to develop gradually and are consistent with many other diseases. Symptoms include

  • Lethargy
  • Shortness of breath upon exertion
  • Pale skin
  • Discomfort in warm temperatures
  • Fever
  • Unexplained weight loss
  • Feeling full after eating a small amount of food
  • Night sweats.


What is the treatment for CML?

Because of the advancement of a class of medications known as tyrosine-kinase inhibitors (TKIs), a number of treatment options are available for CML. Treatment is generally based on phase at time of diagnosis, extent of disease, and prognostic score.

  • Imatinib mesylate: Imatinib (Gleevec®) was the first of the TKIs targeting BCR-ABL specifically. It is now known as a first-generation TKI, and after clinical trials demonstrating its efficacy over interferon/cytarabine, was approved as first-line treatment in 2002. Most patients initially respond to imatinib mesylate.
  • Dasatinib: Dasatinib (Sprycel®) is a second-generation TKI that is active against nearly all imatinib-resistant BCR-ABL mutations. Studies demonstrate that dasatinib is effective in inducing cytogenetic and hematologic responses in patients who exhibit imatinib resistance, in all phases of CML. Dasatinib was approved by the U.S. Food and Drug Administration (FDA) in 2006 for patients with CML resistant to or intolerant of imatinib. Dasatinib was then approved as first-line therapy in previously untreated patients with chronic-phase, Philadelphia chromosome-positive CML in 2010, after studies demonstrated that dasatinib achieved response rates similar to high-dose imatinib and superior to standard-dose imatinib.
  • Nilotinib: Nilotinib (Tasigna®) is a highly selective BCR-ABL TKI that is 20-50 times more potent when used against imatinib-resistant cells. In 2007, the FDA approved nilotinib for adult patients with chronic-phase or accelerated-phase Philadelphia chromosome-positive CML with demonstrated intolerance to or resistance of prior imatinib therapy. In 2010, the FDA approved nilotinib as first-line therapy for adult patients newly diagnosed with Philadelphia chromosome-positive CML.

Advanced CML Treatment Options

The National Comprehensive Cancer Network recommends clinical trial participation for all patients in accelerated or blast phase CML.

  • High-dose combination chemotherapy (chemotherapy plus imatinib, dasatinib, or nilotinib)
  • Chemotherapy plus dasatinib or nilotinib for patients with Philadelphia chromosome-positive blast phase CML
  • Dasatinib or nilotinib alone for patients who progress to accelerated phase following initial TKI therapy
    • The use of allogeneic hematopoietic stem cell transplant (allo-HSCT) has decreased. Because of the TKIs, allo-HSCT is no longer recommended as first-line treatment for chronic phase CML. It is recommended for patients with T315I mutation and for those who progress to accelerated or blast phases.
    • Patients who enter cytogenetic relapse or increasing molecular relapse following allo-HSCT may consider imatinib, dasatinib, donor leukocyte infusions, interferon, or PEG-interferon as treatment options (National Comprehensive Cancer Network, 2011).
    • Long- term data confirm that 10%–20% of patients treated with interferon alpha have a complete cytogenetic response (National Cancer Institute,  2011a).

To learn more about CML, its presentation, symptoms, treatment options, and nursing management, visit the Details pages.

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