An Overview of Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a chronic type of leukemia that tends to grow and progress slowly. It is a type of myelogenous leukemia that starts in myeloid cells, which are a type of immature white blood cell (WBC).

CML is one of the four major categories of leukemia. The other three are acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).

Scientist using microscope
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All leukemias begin in the blood-forming cells in the bone marrow. Each type of leukemia is named based on how fast the cancer tends to grow (acute cancer grows fast; chronic grows slowly) as well as the type of blood-forming cells from which the malignancy developed.

What Causes CML?

Certain changes in DNA can cause normal bone marrow cells to become leukemia cells.

People with CML generally have the Philadelphia chromosome, which contains the abnormal BCR-ABL gene. The BCR-ABL gene causes WBCs to grow in an abnormal, uncontrolled way, leading to leukemia.

Who Gets CML?

CML can occur at any age, but it is more common in adults over the age of 50, who account for nearly 70 percent of all cases. Kareem Abdul-Jabbar is a famous American who was diagnosed with CML.

How Common Is CML?

CML is relatively rare. The American Cancer Society reports that for the year 2021, up to 9,110 new cases will be diagnosed, including 5,150 in men and 3,960 in women, resulting in 1,220 deaths, including 680 men and 540 women.

Symptoms

Because CML is a slow-growing cancer, many people do not have symptoms at the time of diagnosis. Some with leukemia do not have any symptoms at all, and are diagnosed based on abnormalities detected with routine blood work.

CML may cause symptoms as it progresses with time.

The most common symptoms, according to the Cleveland Clinic include:

  • Extreme tiredness or fatigue
  • Weakness
  • Fever
  • Night sweats
  • Unexplained weight loss
  • Pain or fullness in the upper left abdomen, beneath the ribs
  • Swollen lymph nodes
  • Frequent infections
  • Shortness of breath
  • Easy bruising and bleeding
  • Bone and joint pain
  • Pale skin

Abdominal fullness develops due to splenomegaly (enlargement of the spleen), which occurs in those with CML. The spleen normally stores blood cells and destroys old blood cells. In CML, the spleen may become enlarged because of all the extra WBCs occupying the organ. Splenomegaly can produce pressure on nearby organs, like the stomach, which may contribute to a sense of becoming full after eating just small amounts of food.

Weakness and fatigue can be caused by anemia, a deficiency of red blood cells (RBCs) that carry oxygen to the tissues. Anemia can make you feel like you won’t be able to exert yourself or use your muscles as vigorously as usual.

Diagnosis

When you are being evaluated for possible leukemia, your healthcare provider will take your medical history and do a physical exam. And you would have many of these same preliminary diagnostic steps even if you are getting a routine medical checkup. Along with an enlarged spleen size, lab, gene, and imaging tests accurately detect CML, according to the American Cancer Society.

Spleen Size

Normally, your spleen can't be felt on a physical exam, but an enlarged spleen can be detected during a physical exam. It can cause a fullness on the left side of the upper abdomen, beneath the edge of the rib cage.

Lab Tests

Too many WBCs and abnormal levels of certain chemicals in the blood may be indicative of CML. These are often described as blasts (immature WBCs) based on their appearance.

If your blood tests are consistent with CML, you may need to have a bone marrow aspiration. This involves a procedure in which a needle is inserted deep into your bone to collect a sample of blood cells. The sample is examined with a microscope. In CML, excess blood-forming cells are present and the marrow is described as hypercellular.

Gene Tests

Gene testing will also be done to see if you have the Philadelphia chromosome and/or the BCR-ABL gene. If you do not have the Philadelphia chromosome or the BCR-ABL gene, then you may have another type of cancer, but it isn't CML.

Imaging Tests

Diagnostic imaging tests are not needed to diagnose CML. However, they might be performed as part of the assessment of certain symptoms or to evaluate abdominal swelling.

Phases of CML

CML can be classified into three different phases. The phase is based on the number blasts in your blood and bone marrow. Knowing the phase of your CML can help you to get a sense of how your illness will affect you in the future.

Chronic Phase

In the first phase of CML, you would have an increased number of WBCs in the blood and/or bone marrow. However, blasts should still make up less than 10 percent of cells.

Usually, in the chronic phase, there are no symptoms, but there can be some fullness of the upper left abdominal area. Your immune system should still be functioning pretty well in the chronic phase, so you can put up a good fight against infections. A person can be in the chronic phase for as short as a few months to as long as many, many years.

Accelerated Phase

In the accelerated phase, the number of blasts in the blood and/or bone marrow is higher than in the chronic phase. Symptoms may include fever, weight loss, decreased appetite, and an enlarged spleen.

The number of WBCs is higher than normal and you can have other changes in your blood counts, such as a high number of basophils (a type of WBC) or a low number of platelets.

There are different sets of criteria used to define the accelerated phase. The World Health Organization (WHO) Criteria defines the accelerated phase as the presence of any of the following:

  • 10 to 19% blasts in the bloodstream and/or bone marrow
  • More than 20% basophils in the bloodstream
  • Very high or very low platelet count that is not related to treatment
  • Increasing spleen size and high WBC count despite treatment
  • New genetic changes or mutations

Blast Phase

This phase is often referred to as blast crisis. It is the third and final stage and has the potential to be life-threatening. The number of blasts in the blood and/or bone marrow becomes very high and they can spread to other tissues. Symptoms are much more common in the blast phase and may include infections, bleeding, abdominal pain, and bone pain.

In the blast phase, CML may appear more like AML (acute myeloid leukemia) or ALL (acute lymphoblastic leukemia) than chronic leukemia.

The WHO defines the blast phase as greater than 20% blast cells in the bloodstream or bone marrow. The International Bone Marrow Transplant Registry defines the blast phase as greater than 20% blast cells in the blood and/or bone marrow. Both definitions also include the presence of blast cells outside of the blood or bone marrow.

Prognosis

The phase of your CML is an important factor in your prognosis, but it’s not the only factor.

Your age, the size of your spleen, and your blood counts are also used to place you in one of three categories: low, intermediate, or high-risk.

People in the same risk group are more likely to respond in a similar way to treatment. People in the low-risk group generally respond better to treatment. However, these groupings are tools, not absolute indicators.

CML Treatments

All treatments have potential risks and benefits, and your CML treatment will be preceded by a discussion with your healthcare provider about the risks and your tolerance for side effects. Not every person with CML receives every CML treatment discussed below.

Tyrosine Kinase Inhibitor Therapy

Tyrosine kinase inhibitor therapy is a type of targeted therapy that inhibits the action of the abnormal BCR-ABL gene. These drugs come in the form of pills that can be swallowed.

Therapy

Description

Imatinib

Was the first tyrosine kinase inhibitor approved by the FDA to treat CML; approved in 2001.

Dasatinib

Was approved for the treatment of CML in 2006.

Nilotinib

Was first approved to treat CML in 2007.

Bosutinib

Approved to treat CML in 2012, but only approved for people who have been treated with another tyrosine kinase inhibitor that has stopped working or caused very bad side effects.

Ponatinib

Approved to treat CML in 2012 but is only approved for patients with a T315I mutation or CML that is resistant or intolerant to other tyrosine kinase inhibitors.

Immunotherapy

Interferon is a substance that the immune system naturally makes. PEG (pegylated) interferon is a long-acting form of interferon.

Interferon is not used as initial treatment for CML, but for some patients, this may be an option when they are unable to tolerate tyrosine kinase inhibitor therapy. Interferon comes as a liquid that is injected under the skin or into a muscle with a needle.

Chemotherapy

Omacetaxine is a chemotherapy drug used for treating CML that's resistant to other treatments and/or if you have an intolerance to two or more tyrosine kinase inhibitors. Resistance is when CML does not respond to a treatment or if the disease responds at first but then stops responding. Intolerance is when treatment with a drug must be stopped due to severe side effects.

Omacetaxine is given as a liquid that is injected under the skin with a needle. Other chemotherapy drugs may be injected into a vein or may be given as a pill to swallow.

Hematopoietic Cell Transplant (HCT)

An HCT is a procedure that replaces cells in your bone marrow with new, healthy blood-forming cells. High-dose chemotherapy is used before the procedure to destroy both normal cells and CML cells in the bone marrow.

An allogeneic HCT is a complex treatment and can cause very serious side effects. It is usually considered as a treatment option for patients younger than 65 years of age.

Clinical Trials: Investigational Therapies

New drugs for the treatment of CML are continuously being investigated. Clinical trials may be an option for some patients. You can ask your treatment team if there is an open clinical trial that you can join and whether or not they believe you would be a good candidate for such a clinical trial.

A Word From Verywell

Your CML prognosis depends on factors such as your age, disease phase, the number of blasts in your blood or bone marrow, the size of your spleen at diagnosis, and your overall health.

With the introduction of tyrosine kinase inhibitors in 2001, many people with CML have done very well, and the disease can often be kept in the chronic phase for years.

Still, a number of challenges remain: it can be difficult to predict, from the start, which patients with CML are likely to have poor outcomes. Additionally, most patients need to take treatment indefinitely, and suppressive treatments are not without side effects. So, while advances have been significant in recent decades, there is still room for further improvement.

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3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Pophali PA, Patnaik MM. The role of new tyrosine kinase inhibitors in chronic myeloid leukemia. The Cancer Journal. 2016;22(1):40-50. doi. 10.1097/PPO.0000000000000165, Published January/February, 2016.

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Additional Reading
  • Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341(3):164-172.
  • National Cancer Institute. Chronic Myelogenous Leukemia Treatment.
  • Thompson PA, Kantarjian HM, Cortes JE. Diagnosis and treatment of chronic myeloid Leukemia in 2015. Mayo Clin Proc. 201 5;90(10):1440-54.