Childhood Chronic Myeloid Leukemia

Chronic myeloid leukemia, also called chronic myelogenous leukemia and CML, is a form of leukemia (blood cancer) that develops in the bone marrow, the soft, spongy center of long bones. CML is a cancer of a subtype of white blood cells called a "myeloblast." Normal myoblasts grow, divide, and mature into white blood cells capable of fighting infections. This process is controlled by the body through complex signaling networks. In a patient with CML, the bone marrow makes abnormal myeloblasts that don't respond to these normal signals and as a result produce large amounts of abnormal white blood cells in an uncontrolled manner. These abnormal cells do not fight infections, but spill into the blood in large numbers, causing a variety of serious problems.

CML is very rare in children. Approximately 150 children in the U.S. are diagnosed with CML each year. Children and teens with chronic myeloid leukemia are treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center through the Childhood Leukemia Program.

Dana-Farber/Boston Children's offers a wide array of support services and programs for pediatric patients and their families during and after cancer treatment.

Phases of Childhood CML

Chronic myeloid leukemia (CML) can be divided into three distinct phases, or stages of development:

• Chronic phase — During this period, there may be no, or few, symptoms of leukemia. However, abnormal types and numbers of cells are discovered in the blood and bone marrow. This phase can last several months to several years.
• Accelerated phase — In this period, an increased number of "blast cells" are found in the blood and bone marrow. The presence of blasts cells indicates the disease is becoming more aggressive or advanced.
• Blastic phase (also known as a "blast crisis") — During this phase, more than 30 percent of bone marrow cells are blast cells. This phase of CML can be very difficult to differentiate from acute lymphoblastic leukemia.

Symptoms of Childhood CML

The symptoms of CML are related to the phase of the disease and often vary from child to child. Patients with chronic phase CML sometimes have no symptoms of the disease and CML may be discovered when your child is having a routine blood test for other reasons. Patients in the accelerated phase or blast crisis often have symptoms related to abnormal bone marrow function.

The most common symptoms of childhood CML include:

Chronic phase CML symptoms

• General fatigue and weakness.
• Abdominal pain may be a symptom of leukemia, since leukemia cells can infiltrate into the liver and spleen, causing enlargement of these organs. Pain in the abdomen may cause your child to lose his or her appetite and lose weight. .
• Recurrent infections. Although your child may have an unusually high number of white blood cells, these cells are immature and do not fight infection. Your child may have had several viral or bacterial infections over the past few weeks and may show symptoms of an infection such as fever, runny nose, and cough.

Accelerated or blast phase CML symptoms

• Abnormal bleeding or easy bruising from decreased production of platelets in the bone marrow.
• Anemia from decreased production of platelets in the bone marrow.
• Serious infections from decreased production of normal white blood cells in the bone marrow.
• Bone and joint pain. Your child may experience pain in his bones and joints that results from the bone marrow being overcrowded and "full."
• Swollen lymph nodes. Your child may have swelling in the lymph nodes under the arms, in the groin, chest, and in the neck. Leukemia cells may collect in the nodes, causing swelling.

These are general symptoms of the disease, but do not include all possible symptoms. It's important to have your child evaluated by a qualified medical professional right away for an accurate diagnosis and prompt treatment.

Causes of Childhood CML

It is not known what causes leukemia, including CML. In the majority of childhood leukemias, gene mutations and chromosome abnormalities in the leukemia cells occur by chance. The abnormalities found in leukemia cells are not found in the other cells of the body.

Nearly all cases of CML are associated with a specific type of genetic abnormality called a chromosomal translocation. In this translocation, part of chromosome #9 breaks off and attaches itself to part of chromosome #22. The resulting abnormal chromosome, often called the "Philadelphia chromosome," forms an abnormal gene called BCR-ABL. This gene makes an abnormal protein which drives the development of the abnormal myeloblasts.