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Chronic Myelocytic Leukemia (CML)

by Michael E. Rytting, MD

Chronic myelocytic (myeloid, myelogenous, or granulocytic) leukemia is a disease in which cells that normally would develop into neutrophils, basophils, eosinophils, and monocytes become cancerous.

  • 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.

CML has three phases

  • Chronic phase: An intial 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.

Symptoms and Diagnosis

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.

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, are often seen.

Tests that analyze chromosomes (cytogenetics or molecular genetic testing) are needed to confirm the diagnosis by detecting the Philadelphia chromosome.

Prognosis and Treatment

Previously, treatments did not cure CML but they did slow its progress. The drug imatinib and similar newer drugs block the abnormal protein produced by the Philadelphia chromosome and have changed the treatment and prognosis of CML.

These drugs 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. Stem cell transplantation (see Stem Cell Transplantation) combined with high-dose chemotherapy may result in a cure. Several other drugs are successful in treating people whose disease is resistant to imatinib, and these drugs may also be used in people with CML that does not respond well to imatinib.

These drugs 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.

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