Chronic Myelogenous Leukemia
(CML)

Chronic Myelogenous Leukemia (CML): Overview

Alternative Names: Chronic Granulocytic Leukemia, Chronic Myelocytic Leukemia, Chronic Myeloid Leukemia, Chronic Myelogenous Leukemia.

Chronic Myeloid Meukemia (CML) is a type of cancer that starts in the blood-forming cells of the bone marrow and invades the blood.  It is usually associated with a chromosome abnormality called the Philadelphia chromosome.  In CML, leukemia cells tend to build up in the body over time, but in many cases people don't have any symptoms for at least a few years.  In time, the cells can also invade other parts of the body, including the spleen.  CML can also change into a fast-growing acute leukemia that invades almost any organ in the body.

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Leukemia is different from other types of cancer that start in organs such as the lungs, colon, or breast and then spread to the bone marrow.  Cancers that start elsewhere and then spread to the bone marrow are not leukemia.

Incidence; Causes and Development; Contributing Risk Factors

About 4,400 new cases of Chronic Myelogenous Leukemia (CML) are diagnosed each year in the United States.

Most cases of chronic myelogenous leukemia occur in adults, but children may develop the disease.  Chronic myelogenous leukemia accounts for about 4% of childhood leukemia cases.  Childhood cases (under 20 years of age) represent about 2% of all patients who develop chronic myelogenous leukemia.  The frequency of the disease increases with age from about one in 1 million children in the first 10 years of life to one in 100,000 people at age 50, to one in 10,000 people at age 80 and above.  The disease in children is similar in behavior to that of adults; however, the outcome of stem cell transplantation is better in younger individuals.

Men are more likely than women to develop the condition.  People aged 45-50 are the most likely to develop the condition.
Exposure to intense radiation may increase the risk of developing the condition.

CML results from an acquired (not inherited) injury to the DNA of a stem cell in the marrow.  This injury is not present at birth.  Scientists do not yet understand what produces this change in the DNA in patients with CML.  This change in the stem cell's DNA confers a growth and survival advantage on the malignant stem cell.  The result of this injury is the uncontrolled growth of white cells leading, if unchecked, to a massive increase in their concentration in the blood.  Unlike acute myelogenous leukemia (AML), chronic myelogenous leukemia permits the development of mature white blood cells that generally can function normally.  This important distinction from acute leukemia accounts for the less severe early course of the disease.

Chronic myelogenous leukemia is distinguished from other leukemias by the presence of a genetic abnormality in blood cells, called the Philadelphia chromosome.  The changes that result in this chromosome "causing" chronic myelogenous leukemia have been studied intensively.  In 1960, two physicians studying chromosomes in cancer cells noticed that a chromosome in CML patients was shorter in length than that of the same chromosome in normal cells.  They named this shortened chromosome the Philadelphia chromosome, because the observation was made at the University of Pennsylvania School of Medicine in that city.

The total of 46 chromosomes in normal human cells is composed of 22 pairs of chromosomes numbered 1 to 22 and two sex chromosomes (either an X and Y in males or two Xs in females).  The Philadelphia chromosome (No. 22), which is an abnormally short chromosome, is usually referred to as the Ph-chromosome.

Further studies established that two chromosomes, usually chromosome Nos.  9 and 22, were abnormal.  Pieces of the chromosomes, which are broken off in the blood cells of patients with chronic myelogenous leukemia, switch with each other.  The detached portion of chromosome 9 sticks to the broken end of chromosome 22, and the detached portion of chromosome 22 sticks to the broken end of chromosome 9.  This abnormal exchange of parts of chromosomes is called a translocation.  This translocation of chromosome pieces occurs only in the stem cell and in the various blood cells derived from that stem cell.  The chromosomes of the cells in other tissues are normal.

The cause of the chromosomal breakage in virtually all CML patients is not known.  In a small proportion of patients, the cause of the breakage is exposure to very high doses of radiation.  This effect has been most carefully studied in the Japanese survivors of the atomic bomb, whose leukemia risk was significantly increased.

A slight increase in risk also occurs in some individuals treated with high dose radiotherapy for other cancers, such as lymphoma.  Exposures to diagnostic dental or medical X-rays have not been associated with a heightened risk of chronic myelogenous leukemia.

Signs and Symptoms

The onset of chronic myelogenous leukemia is associated with symptoms that usually develop gradually.  Most patients feel fatigue and a loss of well-being (general malaise).  They tire more easily and may feel short of breath when physically active.  They may have a pale complexion from anemia.  Discomfort on the left side of the abdomen from an enlarged spleen is a frequent complaint.  Patients may experience fever, excessive sweating, night sweats, weight loss, reduced appetite, an inability to tolerate warm temperatures, bone or joint pain, heart attack or stroke, gastrointestinal bleeding, infection.

Diagnosis and Tests

Increasingly, the disease is discovered during the course of a "routine" medical examination.  Since the disease worsens over weeks or months, most patients would have symptoms develop soon after such a medical examination in any case.

To diagnose the disease, the blood and, in most cases, the marrow cells must be examined.  The white cell count invariably increases, often to very high levels.  Examination of the stained (dyed) blood cells with a light microscope shows a characteristic pattern of white cells: a small proportion of very immature cells (leukemic blast cells), and a larger proportion of maturing and fully-matured white cells (myelocytes and neutrophils).

Treatment and Prevention

Treatment options for CML have expanded greatly and may include: chemotherapy, biologic therapy, high-dose chemotherapy with stem cell transplant, donor lymphocyte infusion (DLI), surgery.

Targeted drugs affect a specific protein that lets cancer cells multiply.  These drugs include Dasatinib (Sprycel), Imatinib (Gleevec), and Nilotinib (Tasigna).

Interferon helps the immune system combat cancer cells.  Used only if bone marrow transplant is not an option.

Chemotherapy drugs such as cyclophosamide and cytarabine are often combined with other treatments to kill cancer cells.

Signs, symptoms & indicators of Chronic Myelogenous Leukemia (CML):

Lab Values - Cells

(Somewhat/highly) elevated basophil count

Basophil levels are normally very low, but a high basophil count can indicate a problem with the production and growth of blood cells in the bone narrow, as occurs in myeloproliferative disorders.

Symptoms - Skin - General

Conditions that suggest Chronic Myelogenous Leukemia (CML):

Lab Values

Neutrophilia

Chronic myelocytic leukemia is a myeloproliferative disorder that causes proliferation of bone marrow cells.

Musculo-Skeletal

Gout / Hyperuricemia

One complication of CML is gout, caused by marrow hyperproliferation.

Tumors, Malignant

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Chronic Myelogenous Leukemia (CML) suggests the following may be present:

Circulation

Nutrients

Tumors, Malignant

Chronic Myelogenous Leukemia (CML) can lead to:

Musculo-Skeletal

Gout / Hyperuricemia

One complication of CML is gout, caused by marrow hyperproliferation.

Recommendations for Chronic Myelogenous Leukemia (CML):

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