What Is Chronic Myeloid Leukemia?

Understanding CML: Overview, Symptoms, Prognosis

Scientist Viewing Cell Culture with Inverted Microscope
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Chronic myeloid leukemia (CML) is one of the four major categories of leukemia. The other three are acute myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphocytic leukemia.

Regardless of the type, all leukemias begin in the blood-forming cells in the bone marrow. Each type of leukemia gets its name from how fast the cancer tends to grow (acute cancer grows fast; chronic grows slowly) and also the type of blood-forming cells from which the malignancy developed.

CML is a chronic leukemia, meaning it tends to grow and progress slowly. CML is also a myelogenous leukemia, meaning it starts in immature white blood cells known as myeloid cells.

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 white blood cells to grow in an abnormal, uncontrolled way, causing 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 one famous American who has CML.

How Common Is CML?

CML is relatively rare. In the United States in 2017, the estimates were that 8,950 new cases would occur and an estimated 1,080 people would die of this disease.

Symptoms

Because CML is a slow-growing cancer, many people do not have symptoms when they are first diagnosed.

In fact, up to 40 to 50 percent of patients do not have any symptoms at all, and they receive their diagnosis after routine blood work detects an abnormality.

CML may cause symptoms as it progresses with time, however. Given this situation, the list of “most common symptoms” can be described as follows:

  • No symptoms (up to 50 percent of people at diagnosis)
  • Extreme tiredness or fatigue
  • Weakness
  • Fever
  • Night sweats
  • Unexplained weight loss
  • Pain or fullness in the upper left abdomen, beneath the ribs.

The last symptom in the list is due to an enlarged spleen, also called splenomegaly, which is present in 46 to 76 percent of those with CML. Such enlargement of the spleen can result in less space for the other organs in the area, like the stomach, which may contribute to a sense of becoming full early when eating a meal.

The weakness and fatigue that some people with CML experience can develop from a number of different sources. One source of weakness and fatigue is anemia, which means the body does not have enough healthy red blood cells that carry oxygen to the tissues. Anemia can also make you feel like you won’t be able to exert yourself or use your muscles as vigorously as usual.

Diagnosis

Your doctor will take your medical history and perform a physical exam, just like any other evaluation for an illness.

Spleen Size

Checking the size of your spleen is an important part of the physical exam. A normal-sized spleen is not normally felt, but an enlarged spleen can be detected on the left side of the upper abdomen, beneath the edge of the rib cage.

The spleen normally stores blood cells and destroys old blood cells. In CML, the spleen may become enlarged because of all the extra white blood cells occupying the organ.

Lab Tests

Laboratory tests are also needed. Blood is usually taken from a vein in the arm, and bone marrow is sampled through a procedure called a bone marrow aspiration and biopsy. Your samples are sent to a lab and a pathologist examines them under the microscope and performs other tests, looking to find and further describe the leukemia cells, if present.

Too many white blood cells and abnormal levels of certain chemicals in the blood may be indicative of CML.

In the bone marrow samples, when more blood-forming cells are present than is expected, the marrow is said to be hypercellular. Bone marrow is often hypercellular in CML because it is full of leukemia cells.

Gene Tests

Gene testing will also be done to look for “the Philadelphia chromosome” and/or the BCR-ABL gene. This type of test is used to confirm the diagnosis of CML. If you do not have the Philadelphia chromosome or the BCR-ABL gene, then you do not have CML.

Imaging Tests

Scans, or imaging tests, are not needed to diagnose CML. However, they might be performed as part of your workup, in some instances; for example, to investigate certain symptoms or to see if there is enlargement of the spleen or liver.

Phases of CML

Cases of CML can be classified into three different groups called phases. The phase is based on the number of immature white blood cells, or blasts, that you have in the 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

This is the first phase of CML. In this phase, you already have an increased number of white blood cells in the blood and/or bone marrow. However, these immature white blood cells, or blasts, make up less than 10 percent of cells in the blood and/or bone marrow.

Usually, in the chronic phase there are no symptoms, but there can be some upper left abdominal fullness. Your immune system is still functioning pretty well in the chronic phase, so you still have the ability to 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 blast cells in the blood and/or bone marrow is higher than in the chronic phase and the leukemia cells grow to cause symptoms which may include fever, weight loss, not feeling hungry, and an enlarged spleen.

The number of white blood cells is higher than normal and you can have changes in your blood counts, such as a high number of basophils or a low number of platelets.

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

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

Blast Phase

This is also referred to as “blast crisis,” since it is the third and final stage and has the potential to be life-threatening. The number of blast cells in the blood and/or bone marrow becomes very high and these blast cells spread outside the blood and/or bone marrow to other tissues. Symptoms are much more common in the blast phase, which may include infections, bleeding, abdominal pain, and bone pain.

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

The WHO definition for blast phase is greater than 20 percent blast cells in the bloodstream or bone marrow. The International Bone Marrow Transplant Registry definition of blast phase is greater than 30 percent blast cells in the blood and/or bone marrow. Both definitions include the presence of blast cells outside of the blood or bone marrow.

Prognosis

When trying to predict your prognosis, the phase of your CML is an important factor, but it’s not the only factor.

There are several other items that have been shown to correlate with your risk as an individual patient, including your age, the size of your spleen, and blood counts. Based on such factors, a person can fall into 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 the decision to treat CML is one that is made by having doctor-patient conversations and evaluating the particular individual patient and his or her disease and overall health. 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. What is the target? This group of drugs targets the abnormal BCR-ABL protein that helps CML cells grow.

These drugs inhibit the BCR-ABL protein from sending the signals that cause too many CML cells to form. 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 the drug.

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 is a liquid that is injected under the skin or into a muscle with a needle.

Chemotherapy

Omacetaxine is a newer chemotherapy drug that was approved for CML in 2012, in patients with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Resistance is when CML does not respond to a treatment. 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 they may be given as a pill to swallow.

Hematopoietic Cell Transplant (HCT)

Before tyrosine kinase inhibitors, this was considered the treatment of choice for CML, but an allogeneic HCT is a complex treatment and can cause very serious side effects. Thus, it may not be a good treatment choice for every patient with CML, and many treatment centers today only consider this treatment option for patients younger than 65 years of age.

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

Clinical Trials: Investigational Therapies

New drugs are continuously being researched. Clinical trials of new therapies may be an option for some patients. You can always 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

For the individual with CML, the prognosis can depend on factors such as age, the phase of CML, the amount of blasts in the blood or bone marrow, the size of the spleen at diagnosis, and overall health.

With the introduction of drugs called tyrosine kinase inhibitors starting 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 the CML treated 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.

Sources:

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.

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.

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