Section 14. Blood Disorders

Chapter 176. Leukemias

Topics: Introduction | Acute Lymphocytic Leukemia | Acute Myelocytic Leukemia | Chronic Lymphocytic Leukemia | Chronic Myelocytic Leukemia

Chronic Myelocytic Leukemia

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

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.

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 immature blasts are seen, 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 blast crisis. In blast crisis, only immature leukemia cells are produced, a sign that the disease has become much worse. Massive enlargement of the spleen is common in blast crisis, as well as fever and weight loss.

Symptoms and Diagnosis

Early on, in its chronic stage, CML may produce 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 blast crisis, people become sicker because the number of red blood cells and platelets decreases, leading to paleness, bruising, and bleeding.

The diagnosis of CML is suspected based on the results of a simple blood test. The test may 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 seen.

Tests that analyze chromosomes (cytogenetics or molecular genetics) are needed to confirm the diagnosis. Chromosomal analysis of the leukemia cells always shows 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.

Prognosis and Treatment

Although most treatments do not cure the disease, they do slow its progress. About 20% of people who have CML die within 2 years of the diagnosis, and about 15 to 20% die each year after that. However, more than 50% of people with CML survive 4 to 5 years or more after the diagnosis, ultimately dying during the accelerated phase or a blast crisis. Treatment of a blast crisis is similar to treatment of acute leukemia. The average survival time after a blast crisis is only 2 months, but chemotherapy can sometimes extend survival to 8 to 12 months.

Treatment in the chronic phase is considered successful if the white blood cell count is reduced to no more than what would be considered a moderately high level. Even the best treatment cannot destroy all of the leukemia cells. The only chance for cure is high-dose chemotherapy with stem cell transplantation (see Section 16, Chapter 187). The transplantation of stem cells--which must come from a donor who has a compatible tissue type, usually a sibling--is most effective during the early stages of the disease and is considerably less effective during the accelerated phase or blast crisis.

Hydroxyurea, which can be taken by mouth, is the most widely used chemotherapy drug for CML. The drug interferon-alpha helps return the bone marrow to normal function. Interferon-alpha can sometimes reduce the percentage of cells with the Philadelphia chromosome, and some people in whom the chromosome is eliminated enjoy prolonged survival.

A new drug, imatinib, has been found to control blood counts and reduce the Philadelphia chromosome more effectively than interferon-alpha, with many fewer side effects. The drug works by inhibiting the abnormal enzyme produced by the Philadelphia chromosome. Because imatinib is so new, its long-term benefits in terms of prevention or delay of blast crisis remain to be determined. It is also effective initial treatment for blast crisis, although most people eventually relapse.

In addition to chemotherapy, radiation therapy to the spleen is sometimes given to help reduce the number of leukemia cells. Occasionally, the spleen must be surgically removed (splenectomy) to relieve abdominal discomfort, increase the number of platelets, and decrease the need for blood transfusions.

In people for whom stem cell transplantation is not an option, or in people whose transplant fails to cure CML, chemotherapy sometimes provides temporary benefit. When no options are left and the person is clearly at the end of life, then palliative care that focuses on relief of pain and other symptoms is appropriate (see Section 1, Chapter 8).