Chronic myelogenous leukemia (CML)

What is chronic myelogenous leukemia?

Chronic myelogenous leukemia (CML; also known as chronic myeloid leukemia or chronic granulocytic leukemia) is a cancer of the blood system in which too many white blood cells (WBCs) are made in the bone marrow. In the early stages of CML (the chronic phase), these excess WBCs mature normally. In contrast, excess WBCs in late CML (the accelerated and acute phases) do not mature.

Who gets CML?

The American Cancer Society estimates that in 2007 there will be about 4,570 new cases of chronic myelogenous leukemia in the United States, and that about 490 will die of the disease. With the average age of people with CML around 66 years, CML mostly affects adults, although 2 percent of CML patients are children.

What causes CML?

In almost everyone with CML, the genetic material (chromosomes) in the leukemia cells has an abnormal feature called the Philadelphia chromosome (right).

The Philadelphia chromosome results from a mutation called a translocation (two chromosomes break, then parts from each chromosome switch places). In CML, the translocation occurs between chromosomes 9 and 22 (human DNA is packaged in 23 pairs of chromosomes) and produces a new, abnormal gene called BCR-ABL. This abnormal gene produces Bcr-Abl tyrosine kinase, an abnormal protein that causes the excess WBCs typical of CML.

The Philadelphia chromosome is an acquired mutation — that is, a person is not born with it and it is not passed on to their children. Exactly why the Philadelphia chromosome forms is unknown in most cases, although exposure to ionizing radiations (such as during the atomic bomb explosions in Japan) has been shown to cause CML.

What are the symptoms of CML?

In chronic phase CML many people have no symptoms. When symptoms are present, they are often nonspecific and can include signs such as weakness, fatigue, weight loss and fever. These symptoms occur because the leukemia WBCs are replacing normal bone marrow cells. In accelerated and acute phases, symptoms may include lack of appetite, anemia and recurring infections.

How is CML diagnosed?

Because many people with early CML have no symptoms, about half of CML cases are detected when a person visits a doctor for a routine checkup or blood test.

When people do have symptoms, a doctor may order blood tests to examine the different kinds of blood cells present. If the results of the blood test are not normal, the doctor may order more blood tests and a bone marrow exam (or aspiration) may also be done. During the exam, a needle is inserted into the hipbone and a small amount of bone marrow is withdrawn. The bone marrow sample is then examined by chromosome and/or molecular techniques for the presence of the Philadelphia chromosome. Presence of this abnormality is required for a definitive diagnosis of CML.

What are the phases of CML?

CML is divided into three phases depending on the maturity of the leukemia WBCs.

How is CML treated?

Treatment options for people with CML depend on the phase of their disease, age and the availability of a potential donor for a bone marrow or blood cell transplant. Only treatment options for chronic phase CML are discussed in this section.

Chemotherapy

Chemotherapy uses drugs to kill cancer cells. These drugs are usually taken by mouth or administered in a vein or into the skin or tissue. Because the drugs circulate in the blood, they can reach leukemia cells all over the body.

There are four drugs used in the treatment of chronic phase CML. The newest treatment is Gleevec® (imatinib mesylate, Novartis), an oral therapy that is believed to interfere with the action of the abnormal Bcr-Abl tyrosine kinase in CML white blood cells.

• To date, Gleevec treatment has led to hematologic remission (control of WBC levels) in almost all patients.
• In about half of CML patients, Gleevec treatment is also associated with cytogenetic remission, in which the Philadelphia chromosome becomes undetectable.
• However, molecular remission (elimination of CML cells as determined using a more sensitive molecular method called PCR) occurs in less than 10 percent of people who receive Gleevec.
• Overall, it is estimated that about 80 percent of people receiving Gleevec still have the Philadelphia chromosome, either because it was never eliminated or the mutation recurred.

Before Gleevec, the most common drugs used to treat CML were the oral treatments hydroxyurea and busulphan. An intravenous treatment, cytarabine, is sometimes used in combination with immune therapy (discussed below).

Immune therapy

Immune therapy uses the body’s immune system to fight cancer. One type used to treat chronic phase CML is interferon alpha, a regulator of the immune system. Interferon alpha is sometimes combined with cytarabine chemotherapy and can be associated with adverse side effects, some of which are severe. About half of patients receiving interferon alpha discontinue therapy because of these side effects.

Bone marrow transplantation

Bone marrow transplantation is used to replace the CML patient’s unhealthy bone marrow (which produces abnormal blood cells) with healthy bone marrow (that can produce normal blood cells). In the procedure, the patient’s bone marrow is destroyed with high doses of chemotherapy, with or without radiation therapy. Healthy bone marrow or blood cells are then taken from the donor, who has the same genetic type as the patient (an HLA match), and given to the recipient intravenously. Bone marrow transplantation is limited to younger patients (less than 55 years old) with a suitable donor — which is only about 10 percent of people with CML.

Clinical trials

Clinical trials of new immunotherapies or chemotherapy combinations can be important treatment options for CML patients.

Learn more about clinical trials.

What are some questions I can ask my doctor?

Your doctor is your best resource for information so you should feel free to ask any questions that are on your mind. Below are some questions you might want to ask your doctor.

• What treatment choices do I have?
• Which treatment do you recommend, and why?
• What side effects are there to the treatments that you recommend?
• What can I do to help reduce the side effects I may have from treatment?
• What are the chances that my leukemia will come back once I am in remission?

Below are additional resources that may be helpful to you.