Chronic Myeloid Leukemia (CML)

Chronic myeloid (myelogenous) leukemia (CML) is blood cancer that starts in the blood-forming myeloid cells or stem cells in your bone marrow. Healthcare providers treat CML with innovative therapies that have turned CML from being a potentially life-threatening illness into a chronic illness.

What is chronic myeloid leukemia (CML)?

Chronic myeloid leukemia (CML) is blood cancer that starts in the blood-forming myeloid cells or stem cells in your bone marrow. The condition has other names: chronic myelogenous leukemia or chronic granulocytic leukemia. Many people with CML may have normal life spans, thanks to therapy that has turned the condition from a life-threatening illness into a chronic illness that medication can manage.

How common is chronic myeloid leukemia?

CML is relatively common. About 1 in 565 people in the U.S. will develop the condition. Chronic myeloid leukemia represents about 15% of all types of leukemia. You can develop CML at any age, but it typically affects older adults.

How fast does CML progress or get worse?

It takes a long time for CML to get worse. You can have this condition for years before noticing symptoms. Many people learn they have CML after routine blood test results show unusual blood cell counts. Prompt treatment keeps CML from getting worse. Without treatment, chronic myeloid leukemia can become a life-threatening illness within three to four years.

Symptoms and Causes

What are CML symptoms?

You can have CML without having noticeable symptoms. Chronic myeloid leukemia symptoms are mild and get worse over time. Common CML symptoms may include:

• Fatigue or weakness.
• Shortness of breath (dyspnea).
• Fever.
• Night sweats.
• Unexplained weight loss.
• Abdominal swelling or discomfort in the upper left part of your belly, where you can find your spleen.
• Feeling full when you haven’t eaten much.

What causes chronic myeloid leukemia?

People with CML have an acquired genetic mutation or change in myeloid stem cells growing in their bone marrow. Acquired mutations aren’t present at birth and aren’t something you can inherit. Acquired mutations happen during your lifetime.

In genetic mutations, mutated or changed genes give cells new instructions on what to do. In this case, the mutation creates a new fused gene, BCR-ABL. The new gene triggers the following chain of events that lead to chronic myeloid leukemia:

• The BCR-ABL gene gives new instructions to myeloid stem cells.
• The stem cells make an abnormal version of tyrosine kinase enzymes.
• These enzymes help manage cell growth. They act like “on” and “off” switches.
• The abnormal tyrosine kinase enzymes don’t have an “off” switch.
• Without an “off” switch, myeloid stem cells in your bone marrow divide and multiply uncontrollably.
• Over time, abnormal myeloid stem cells in your bone marrow start dividing and multiplying uncontrollably, making unusually large amounts of immature white blood cells (blasts).
• Eventually, the blasts accumulate in your bone marrow, making it hard for your bone marrow to make normal red blood cells, white blood cells and platelets. You may have fewer red blood cells but more platelets and abnormal white blood cells.

What are the risk factors for this condition?

The only risk factor for CML is exposure to high levels of radiation — and this applies to very few people.

What are the complications of this condition?

People with CML may develop:

• Anemia. This condition happens when you don’t have enough red blood cells.
• Enlarged spleen (splenomegaly).

Can CML lead to other types of cancer?

Yes, it can. People with CML may have an increased risk of other types of cancer (second cancers). A recent study showed about 30% of people with chronic myeloid leukemia developed second cancers, including:

• Small intestine cancer.
• Thyroid cancer.
• Stomach cancer.
• Lung cancer.
• Prostate cancer.

Diagnosis and Tests

How is CML diagnosed?

Healthcare providers may suspect you have CML if you have unusual blood test results. But they actually diagnose CML with chromosome or genetic tests that identify genetic changes or mutations. Common tests for CML include:

• Complete blood count (CBC): Providers may check for high levels of white blood cells or low red blood cell levels.
• Bone marrow aspiration or bone marrow biopsy: Providers take small samples of fluid or tissue for genetic tests. A medical pathologist will perform tests to analyze abnormal cells’ genetic makeup.
• Computed tomography (CT) scan: Providers use this test to determine if CML is affecting other parts of your body.
• Ultrasound: Providers may do this test to determine if your spleen is larger than normal. An enlarged spleen is a CML symptom.

What are CML stages?

Unlike many types of cancer, healthcare providers don’t characterize chronic myeloid leukemia by cancer stages. They characterize CML as being in one of four phases:

• Chronic CML:The term “chronic” often means you have a long-term condition. In CML, the term refers to the percentage of blasts (immature white blood cells) in your bone marrow and blood. In chronic CML, blasts make up about 10% of cells in your blood and bone marrow. Between 80% and 90% of people diagnosed with the condition have chronic CML. Some but not all people with chronic CML have symptoms.
• Accelerated CML:In this phase, blasts make up 10% to 19% of cells in your blood or bone marrow. Providers may also look for basophils. Basophils are white blood cells that release enzymes to improve blood flow and prevent blood clots. If you have CML, you may have increased basophil levels.
• Blast (blast crisis) CML:Blast CML can be life-threatening. In blast CML, tests show blasts make up 20% or more of cells in your bone marrow or blood. Most people with blast phase CML have very noticeable symptoms such as extreme fatigue, fever, weight loss and shortness of breath.
• Resistant CML: CML that comes back after treatment or doesn’t respond to treatment is called resistant CML.

Management and Treatment

How is CML treated?

Healthcare providers typically treat chronic phase CML with tyrosine kinase inhibitors (TKIs). TKIs are a type of targeted therapy. In CML, the targets are the abnormal BCR-ABL enzymes that let abnormal white blood cells divide and multiply uncontrollably. TKIs block the enzymes so that CML cells start to die.

TKIs have made a huge difference for people with chronic myeloid leukemia. Before TKIs, only about 20% of people with the condition were alive five years after diagnosis. TKIs changed that outcome for people with early (chronic) CML.

TKIs put chronic myeloid leukemia into remission. (Remission means you don’t have CML symptoms and tests don’t find signs of the disease.) Most people take TKIs for the rest of their lives. However, recent studies show CML remains in remission even after people stop taking TKIs. This is treatment-free remission. Common TKIs to treat chronic phase CML include:

• Imatinib (Gleevec®).
• Dasatinib (Sprycel®).
• Nilotinib (Tasigna®).
• Bosutinib (Bosulif®).
• Ponatinib (Iclusig®).
• Asciminib (Scemblix®).

What are TKI side effects?

Side effects vary based on the specific TKI but may include:

• Stomach pain.
• Fatigue.
• Diarrhea.
• Muscle cramps.
• Edema.
• Pleural effusion (fluid accumulation around your lungs).
• Pancreatitis.
• Damage to your liver.
• Lower-than-normal white blood cell and platelet counts.

What are other CML treatments?

If TKIs aren’t effective, providers may use chemotherapy along with or instead of a TKI.

Prevention

Can CML be prevented?

No, it can’t. Medical researchers know CML happens when a specific gene mutates, but they haven’t discovered why that mutation happens.

Outlook / Prognosis

What can I expect if I have this condition?

That depends on your situation. If treatment puts chronic myeloid leukemia into remission, you won’t have symptoms or signs of disease, but you’ll need medication to keep CML in remission. Most people with CML attend frequent, routine appointments to see how well their treatment is working.

What about treatment-free remission?

Treatment-free remission (TFR) means you don’t have CML symptoms or signs even after you stop taking a TKI. Recent studies show about 40% of people who stop treatment remain in remission for several years. But TFR is a relatively recent approach to treating chronic myeloid leukemia. Not everyone is a candidate. If you have chronic myeloid leukemia, it’s important that you talk to your provider before stopping treatment.

Is CML curable?

Right now, allogeneic stem cell transplantation is the only way to “cure” chronic myeloid leukemia. Allogeneic stem cell transplantation uses donated stem cells. It’s a complicated medical treatment. Its side effects are more serious than targeted therapy side effects. For that reason, providers typically only use stem cell transplantation to treat resistant CML.

What is the survival rate of CML?

When you think about survival rates, it’s important to remember that survival rates can’t predict how long you’ll live. Survival rates are based on other peoples’ experiences. What was true for them may not be true for you.

That being said, overall, 90% of people with CML are alive five years after diagnosis. (Before TKI, only 22% of people with CML were alive at the five-year mark.) If you have CML, your healthcare provider is your best resource for information about what you can expect.

Living With

How do I take care of myself?

If you have chronic myeloid leukemia, you may need to take medication for the rest of your life. You’ll also need regular checkups so your healthcare provider can monitor your overall health. They’ll look for signs that CML has come back and for signs of second cancers.

When should I see my healthcare provider?

In general, you should expect to see your provider every few months for the rest of your life.

What questions should I ask my healthcare provider?

• What phase of chronic myeloid leukemia do I have?
• What are my treatment options?
• What will my treatment feel like?
• Will I be able to work during my treatment?
• How often will you perform blood tests to see how my treatment is working?
• What are the chances CML will go into remission?
• Would a stem cell transplant be helpful in my case?
• Who can I talk to about managing my treatment costs?

Additional Common Questions

What’s the difference between CML and CLL?

CML (chronic myeloid leukemia) and CLL (chronic lymphocytic leukemia) are both types of leukemia that develop in your blood or bone marrow. The difference is that CML starts in your myeloid stem cells. CLL starts in your lymphoid stem cells.