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Chronic Myelogenous Leukemia

(CML; Chronic Myelocytic Leukemia; Chronic Myeloid Leukemia; Chronic Granulocytic Leukemia)

By Michael E. Rytting, MD, Professor, Department of Leukemia, University of Texas MD Anderson Cancer Center; Professor, Department of Pediatrics, University of Texas MD Anderson Cancer

Chronic myelogenous leukemia is a slowly progressing disease in which cells that normally would develop into neutrophils, basophils, eosinophils, and monocytes become cancerous (see Overview of Leukemia).

  • People pass through a phase in which they have nonspecific symptoms such as tiredness, loss of appetite, and weight loss.

  • As the disease progresses, the lymph nodes and spleen enlarge, and people may also be pale and bruise or bleed easily.

  • Blood tests, bone marrow examination, molecular testing, and chromosome analysis are used for diagnosis.

  • Treatment is with imatinib or other related new drugs.

Chronic myelocytic leukemia (CML) may affect people of any age and of either sex but is uncommon in children younger than 10 years. The disease most commonly develops in adults between the ages of 40 and 60. The cause usually is a rearrangement of two particular chromosomes into what is called the Philadelphia chromosome. The Philadelphia chromosome produces an abnormal enzyme (tyrosine kinase), which is responsible for the abnormal growth pattern of the white blood cells in CML. Additional gene abnormalities (called mutations) that make CML more resistant to treatment sometimes occur.

CML has three phases

  • Chronic phase: An initial period that may last months to years during which the disease progresses very slowly

  • Accelerated phase: The disease begins to progress more quickly, treatments are less effective, and symptoms worsen

  • Blast phase: Immature leukemia cells (blasts) appear and the disease becomes much worse, with complications such as serious infections and excessive bleeding

In CML, most of the leukemia cells are produced in the bone marrow, but some are produced in the spleen and liver. In contrast to the acute leukemias, in which large numbers of blasts are present, the chronic stage of CML is characterized by marked increases in the numbers of normal-appearing white blood cells and sometimes platelets. During the course of the disease, more and more leukemia cells fill the bone marrow and others enter the bloodstream.

Eventually the leukemia cells undergo more changes, and the disease progresses to an accelerated phase and then inevitably to the blast phase. In the blast phase, only immature leukemia cells are produced, a sign that the disease has become much worse. Massive enlargement of the spleen is common in the blast phase, as well as fever and weight loss.


Early on, in its chronic stage, CML may cause no symptoms. However, some people become fatigued and weak, lose their appetite, lose weight, develop a fever or night sweats, and notice a sensation of being full—which is usually caused by an enlarged spleen. As the disease progresses to the blast phase, people become sicker because the number of red blood cells and platelets decreases, leading to infections, paleness, bruising, and bleeding.


  • Blood tests

  • Chromosome analysis

The diagnosis of CML is suspected when the results of a simple blood count show an abnormally high white blood cell count. In blood samples examined under a microscope, less mature white blood cells, normally found only in bone marrow, may be seen. However, many times, the circulating white blood cells are normal in appearance.

Tests that analyze chromosomes (cytogenetics or molecular genetic testing) are needed to confirm the diagnosis by detecting the Philadelphia chromosome. If treatment appears to be less effective than expected, people are tested for other mutations that can make CML resistant to treatment.


Previously, treatments did not cure CML but they did slow its progress. Use of newer drugs has increased survival in people with CML.


  • A tyrosine kinase inhibitor, sometimes with older chemotherapy drugs

  • Sometimes stem cell transplantation

The drugs imatinib and dasatinib, as well as similar drugs, are called tyrosine kinase inhibitors (TKIs). These drugs block the abnormal protein produced by the Philadelphia chromosome and have changed the treatment and prognosis of CML.

TKIs are effective and usually cause only minor side effects. More than 90% of people with chronic phase CML who are given imatinib are well 5 years after treatment. Most of them are still well 10 years after treatment. How long treatment with imatinib needs to continue and whether stopping treatment during a remission is safe is not yet known. Several other TKIs are successful in treating people whose disease has become resistant to imatinib or has not initially responded well to imatinib.

TKIs combined with older chemotherapy drugs are now showing success in treating people during the blast phase, which previously resulted in death in a few months.

Stem cell transplantation combined with high-dose chemotherapy may result in a cure in people who do not respond to other therapy.

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