CML is a cancer of the blood. In people with CML, there is a disruption in the process that governs the normal life cycle of white blood cells. As a result, too many white blood cells develop. CML is called myelogenous because it affects a particular white blood cell called the myeloid cell, and it is considered a chronic leukemia because the disease tends to grow slowly over a long period of time.
CML is relatively uncommon. It is estimated that, globally, there is one case of CML for every 100,000 people. CML is usually diagnosed in adults over the age of 40. This form of leukemia rarely occurs in children and is slightly more common in men than in women.
Blood cells start out as stem cells in the bone marrow. These are called hemopoietic stem cells. Different hemopoietic stem cells mature into red blood cells, white blood cells and platelets.
Doctors believe CML starts when a genetic mistake or mutation occurs in a single hemopoietic stem cell. What causes this mutation is unknown, and probably differs for different people. Doctors report an increase in CML and other leukemias following the nuclear bombings of Japan during World War II, so there may be some correlation between high levels of radiation and the development of CML. In very rare instances, doctors believe there may be a slight genetic predisposition to CML.
The Philadelphia Chromosome
While the specific trigger for CML is unknown, doctors understand much of the process by which the disease unfolds. In the vast majority of cases of CML, the disease starts when two chromosomes swap parts during cell division. This is called a translocation. One of the abnormal chromosomes that results is called the Philadelphia chromosome, and this is the distinguishing feature in most cases of CML.
The Philadelphia chromosome contains a unique gene called BCR-ABL which produces an abnormal enzyme, also referred to as BCR-ABL. The abnormal BCR-ABL enzyme interferes with the programmed life cycle of white blood cells. In CML, white blood cells do not die as they normally should. This, and other mechanisms that are only partially understood, leads to the over-production and accumulation of these blood cells.
The Phases of CML
CML has three distinct phases: the chronic phase, the accelerated phase and the blast phase.
- Chronic Phase: During the chronic phase of CML, excessive white blood cells enter the bloodstream. Most of these still function normally. People with CML usually have no or only mild symptoms at this stage of the disease. About 85 percent of patients are in the chronic phase of CML at the time of diagnosis.
- Accelerated Phase: During the accelerated phase of CML, the number of immature white blood cells, called "blasts," increase rapidly in the marrow. This overproduction becomes so rapid there is literally no room for all of them, and they are forced out into the bloodstream. Abnormalities in other blood cells are more likely to occur. More noticeable symptoms during this phase may include fatigue, abdominal pain, bleeding, excessive sweating, weight loss and infection. During this phase, the disease is more difficult to control with medications.
- Blast Phase: During this phase, the number of blast cells in the bloodstream continues to increase, while the number of mature white blood cells and platelets drops. This results in a high risk of bleeding and infection. In the blast phase, CML is very difficult to treat.
Many CML patients will not have any noticeable symptoms at the time of diagnosis. The patient may have an enlarged spleen from the increased production of white blood cells. There may be some abdominal tenderness. There may also be fatigue and slight fever.
Since symptoms often do not occur, or do not cause alarm, many people are diagnosed only following routine blood tests. CML may be suspected when the tests reveal extremely high white blood counts.
A doctor will likely order further tests to confirm the diagnosis. Most commonly, this will be a test on a sample of bone marrow. A chromosome expert will look at hemopoietic cells under the microscope, in a process called cytogenetic testing. If the Philadelphia chromosome is spotted, the diagnosis of CML is confirmed.
Goals of Treatment in CML
The immediate goal in treating CML is to bring the blood counts back to normal. The next goal is to eliminate as many cells as possible containing the abnormal Philadelphia chromosome. Cure is not yet possible with drug therapy. Instead, successful management of CML will keep the disease in its chronic phase, delaying or preventing the progression to the accelerated phase. Some leukemia cells will remain in the body. So it is important to take medicine indefinitely. Otherwise, it is likely the disease will relapse and progress.
Allogeneic Stem Cell Transplants
High dose chemotherapy and sometimes radiation followed by stem cell transplant is the only treatment that can cure CML. However, this can be a high-risk treatment. Large doses of chemotherapy, usually combined with radiation, are administered to destroy all of a patient's blood marrow. This is followed by an allogeneic stem cell transplant from a matched stem cell donor. This transplant rebuilds the marrow, and restores the patient's ability to make new blood cells.
New techniques have been developed to make stem cell transplants less risky than they've been in the past. However, drug therapy has proven so successful in recent years that most doctors recommend avoiding, or delaying, a stem cell transplant. One exception may be very young patients with a suitably matched donor -- most commonly, a sibling. Stem cell transplants remain an important option in some of the rare cases in which drug therapy fails.
Produced in collaboration with the Leukemia & Lymphoma Society and supported through an educational grant from Bristol-Myers Squibb Company