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Chronic Myeloid Leukemia (CML)

(Chronic Myelocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Granulocytic Leukemia)


Ashkan Emadi

, MD, PhD, University of Maryland;

Jennie York Law

, MD, University of Maryland, School of Medicine

Last full review/revision May 2020| Content last modified May 2020
Topic Resources

Chronic myeloid leukemia is a slowly progressing disease in which cells that normally would develop into neutrophils, basophils, eosinophils, and monocytes become cancerous (see also Overview of Leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more ).

  • 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, molecular testing, and chromosome analysis are used for diagnosis.

  • Treatment is with drugs called tyrosine kinase inhibitors and is started even if the person has no symptoms.

  • Sometimes, stem cell transplantation is necessary.

Chronic myeloid 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 (9 and 22) into what is called the Philadelphia chromosome. The Philadelphia chromosome produces an abnormal enzyme (tyrosine kinase), which is responsible for the abnormal growth pattern increased production 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 5 to 6 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.

Symptoms of CML

Early on, in its chronic stage, CML may cause no symptoms. However, some people become fatigued and weak, lose their appetite, lose weight, develop night sweats, and notice a sensation of being full—which is usually caused by an enlarged spleen. Other symptoms include joint pains, ringing in the ears, stupor, and itching. As the disease progresses to the blast phase, people become sicker because the number of red blood cells, neutrophils, and platelets decreases, leading to infections, paleness, bruising, and bleeding. Fever, enlarged lymph nodes, an increase in immature white blood cells, and certain skin rashes are usually signs of advanced disease.

Diagnosis of CML

  • Blood tests

  • Chromosome analysis

The diagnosis of CML is suspected when the results of a complete blood count Complete blood count Doctors select tests to help diagnose blood disorders based on the person's symptoms and the results of the physical examination. Sometimes a blood disorder causes no symptoms but is discovered... read more 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.

Prognosis of CML

Previously, treatments did not cure CML, but they did slow its progress. Use of newer drugs has increased survival in people with CML. With the use of the newer drugs, 90% of people survive at least 5 years and most of them are well 10 years after treatment.

Treatment of CML

  • A tyrosine kinase inhibitor, sometimes with older chemotherapy drugs

  • Sometimes stem cell transplantation

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

TKIs are effective and usually cause only minor side effects. How long treatment with TKIs needs to continue and whether stopping treatment during a remission is safe is not yet known.

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

More Information about CML

The following is an English-language resource that may be useful. Please note that the MANUAL is not responsible for the content of this resource.

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