Leukemia is a cancer of the bone marrow and blood. Ordinarily, healthy blood stem cells divide into two lines: myeloid and lymphoid stem cells, which further divide into mature red and white blood cells.
In leukemia, a mutation occurs which causes the rapid growth of abnormal cells. The leukemic cells overtake the bone marrow and exceed the normal cell population, at which point they prevent the normal blood cells from doing their jobs.
Chronic Myelogenous Leukemia (CML) is caused by an acquired genetic mutation to a single stem cell. A cancerous change takes place in the marrow cells that form neutrophils, which are white blood cells that destroy bacteria and other microorganisms.
Most cases of CML occur in adults 65 years and over and the risk increases with age. The good news is that effective treatments for CML have made it possible for patients with CML to live longer and better and the five-year relative survival rate is 90%.
In Canada it’s expected that this year 355 men and 235 women will be diagnosed with CML.
Causes and Risk Factors
Chronic Myelogenous Leukemia is non-hereditary, and develops spontaneously in most individuals. Being over the age of 65, as well as being male increases the risk of developing CML.
Exposure to very high doses of radiation is also a risk factor. Individuals who have undergone radiation therapy for cancers in the past are at increased risk.
That having been said, most people who have received radiation therapy do not go on to develop CML, and most people diagnosed with CML have never had any exposure to high-dose radiation.
Leukemia is one of the “15 cancers” caused by smoking. Exposure to pesticides has also been linked to leukemia and exposure to radon gas has also been linked to an increased risk for leukemia and a number of other cancers. Being overweight can add to a person’s lifetime risk of CLL and exposure to formaldehyde is associated with an increased risk.
CML can often be diagnosed with a simple count of the white cells of the blood combined with one or two other tests.
Most people with CML do not show any symptoms at the time of diagnosis. CML is usually detected during annual physicals or routine blood tests for other medical conditions.
In people who do have symptoms, signs of the disease develop very gradually over time. They include fatigue, shortness of breath, paleness, night sweats, heat-intolerance, unintentional weight loss and an enlarged spleen.
Types and Prognosis
The five-year survival rate for CML is greater than 90% when treated.
Chromosomes are structures found in the nuclei of the cells where genetic information is stored. Cells from CML patients contain a shortened version of chromosome number 22. This abnormality was named the Philadelphia (Ph) chromosome and it is present in 95% of CML patients.
Research shows that the Philadelphia chromosome results when CML cells undergo a ‘translocation’ between chromosomes 9 and 22. The result of this is a mutated cancer-causing gene called the Bcr-Abl gene which causes white blood cells to divide and multiply out of control.
There are three phases of CML. Most people are diagnosed in the Chronic Phase. This is the earliest and most manageable phase. It is characterized by mild symptoms which resolve promptly once treatment starts.
The Accelerated Phase is next and this is when the disease becomes more aggressive. Fatigue may increase, the spleen may become enlarged and the white cell count may fall to very low levels or rise because of the accumulation of blast cells, while platelet counts decline.
The third phase of CML is called Blast Crisis which is the most aggressive phase. This is when CML becomes life-threatening. During this phase, the number of blast cells increases in both marrow and the blood—the red cell, platelet and neutrophil counts drop and the patient experiences frequent infections and episodes of bleeding.
Diagnosis and Medical Work-up
Various tests are necessary to examine the blood and marrow cells in order to make a diagnosis of CML.
A Complete Blood Count test measures the number and type of cells in the blood. In CML, the hemoglobin concentration declines and the white cell count increases to very high levels. Depending on the severity of the disease, the number of platelets may also fluctuate.
Blood analysis with a ‘light microscope’ shows a characteristic pattern among white cells: a small proportion of immature cells and a larger proportion of maturing and fully matured white cells.
If the diagnosis of CML cannot be confirmed through blood tests, a bone marrow aspiration and a bone marrow biopsy are performed. In bone marrow aspiration a thin needle is inserted to remove a small bone marrow sample for analysis. In bone marrow biopsy, a thicker needle is used to remove sample of the bone marrow and a small piece of the bone.
The presence of the Philadelphia chromosome in the marrow cells confirms the diagnosis of CML.
Fluorescent in Situ Hybridization (FISH), and Polymerase Chain Reaction (PCR) are sensitive genetic tests that may be performed which can detect CML cells.
The goal of treating people with CML is to normalize blood levels. It is recommended that patients with CML seek care and treatment from a physician specializing in leukemia—a hematologist or an oncologist.
With current drug therapies, most people diagnosed with chronic phase CML will live good-quality lives. Initial drug treatment begins with tyrosine kinase inhibitor (TKI) drugs. This type of medication can be taken orally and for most patients, this drug successfully results in a stable remission lasting many years.
Stem cell transplant may be an option for CML patients. If the disease recurs after stem cell transplant or is resistant to interferon therapy, other drugs may be given.
While a patient undergoes any of these treatment options, supportive care is needed to manage the depleted white blood count caused by CML, which renders patients prone to bacterial or fungal infections. Physicians may order immunoglobulin injections to combat such infections, and patients may be given drugs to stimulate white blood cell production to increase the body’s defense against infections.