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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

Reviewed/Revised Oct 2023
Topic Resources

Chronic myeloid leukemia is a slowly progressing disease in which cells that normally would develop into the types of white blood cells White Blood Cells The main components of blood include Plasma Red blood cells White blood cells Platelets read more White Blood Cells called neutrophils, basophils, eosinophils, and monocytes become cancerous and replace normal cells in the bone marrow.

  • 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.

When the leukemia cells crowd out normal blood-producing cells in the bone marrow, there is decreased production of one or more of the following:

Cancerous white blood cells do not function like normal white blood cells so the cells of CML do not help defend the body against infection. The smaller number of healthy white blood cells makes infection more likely.

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.

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 of the inability of the bone marrow to produce enough normal blood cells. Massive enlargement of the spleen is common in the blast phase, as well as fever and weight loss.

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.

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

Chronic Myeloid Leukemia

Prognosis for 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.

More Information

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

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