Chronic myeloid leukemia (CML): Full guide

What is CML?

Chronic myeloid leukemia (CML) is a cancer of the blood-forming cells in the bone marrow. Bone marrow is the soft, spongy tissue inside your bones where blood cells are made. In CML, the marrow makes far too many white blood cells called myeloid cells (also called granulocytes).

CML is caused by a gene change that happens during a person's life. It is not passed down in families. Two chromosomes, 9 and 22, swap pieces. The shortened chromosome 22 is called the Philadelphia chromosome. This swap joins two genes, BCR and ABL1, into one new gene called BCR-ABL. That gene makes a protein that acts like a stuck "on" switch, telling the cells to keep growing.

CML is most common in adults in their 50s and 60s, but it can happen at any age. Many people have no symptoms and are found because of a routine blood test. Others feel tired, lose weight, sweat at night, or feel fullness or pain on the upper left side of the belly from a big spleen.

Before the year 2000, CML was often deadly. Today, pills called tyrosine kinase inhibitors (TKIs) block the BCR-ABL protein. Most people who take their TKI every day and have regular blood tests live close to a normal life span. Some people who do very well can even stop treatment, with careful monitoring.

Phases of CML

CML is described by phase rather than type. The phase is based on how many very young, immature cells (blasts) are in the blood and marrow, and on other blood and gene findings.

Most people (about 9 in 10) are diagnosed in the chronic phase. When treated with a TKI, very few people move on to the more advanced phases.

Chronic phase

The earliest and most common phase. There are few blasts. Symptoms are often mild or absent. TKI pills work very well in this phase.

Accelerated phase

More blasts or other signs that CML is getting harder to control, such as new gene changes or rising counts despite treatment. Some newer systems no longer use this group and instead call it high-risk chronic phase. Treatment is usually changed or strengthened.

Blast phase (blast crisis)

CML acts like an acute leukemia, with many blasts. It can be myeloid or lymphoid. It needs strong treatment right away, often a TKI with chemotherapy, followed by a stem cell transplant if possible.

Philadelphia chromosome-positive ALL (related condition)

A different, fast-growing leukemia that has the same BCR-ABL gene. It is treated as acute leukemia, often with TKIs plus other drugs. It is not the same as CML.

Tests you may have

Tests at diagnosis confirm CML and its phase. After that, the most important test is a blood test called BCR-ABL PCR. It measures how much of the CML gene is left in your blood. You will have it often, for as long as you have CML.

Other blood tests check how your body is handling treatment. A repeat bone marrow test is only needed if treatment is not working as expected.

Complete blood count (CBC)

Measures white cells, red cells, and platelets. In CML the white cell count is often very high, and platelets may be high too. The blood count usually returns to normal within weeks of starting a TKI.

Blood smear

A lab expert looks at your blood under a microscope to count blasts and other young cells.

Bone marrow aspirate and biopsy

A needle takes a small sample of marrow, usually from the back of the hip bone, after numbing medicine. It is done at diagnosis to confirm the phase and look at chromosomes. It is not usually needed again unless treatment is not working as expected.

Chromosome test (cytogenetics) and FISH

Tests that look for the Philadelphia chromosome and any extra chromosome changes. Extra changes can mean higher risk.

BCR-ABL PCR (quantitative)

A very sensitive blood test that measures how much BCR-ABL gene is in your blood. The result is given as a percent on the International Scale (IS). Lower is better. It is usually done every 3 months, and less often once results are low and stable.

BCR-ABL mutation test

If your BCR-ABL level rises or does not drop as expected, this test checks for changes in the gene that make some TKIs stop working. It helps choose the next TKI. One change, called T315I, needs specific drugs.

Other blood tests

Liver and kidney tests, blood sugar, cholesterol, and pancreas enzymes are checked before and during treatment, because some TKIs can affect them.

Heart and lung checks

An ECG (heart tracing) may be done before some TKIs, such as nilotinib. Your care team will also review your heart and blood vessel health, which affects which TKI is safest for you.

Phase, risk score, and response goals

CML is not staged by tumor size. Instead, doctors note the phase and give a risk score at diagnosis. Common scores are the Sokal score and the ELTS score. They use your age, spleen size, platelet count, and blast count. A higher risk score may lead your care team to choose a stronger, newer TKI first.

The most important measure over time is how far your BCR-ABL level drops. Doctors compare it to goals, called milestones, at 3, 6, and 12 months. Meeting the milestones means treatment is working well. Missing one does not mean failure. It means your care team will check why, such as missed doses, drug interactions, or a gene change, and may switch your TKI.

Over the long term, the goal is a very low BCR-ABL level that stays low. A deep response for a long time may let some people try stopping treatment.

Milestone at 3 months

BCR-ABL at 10% or lower.

Milestone at 6 months

BCR-ABL at 1% or lower. This usually means no Philadelphia chromosome can be seen on a marrow test.

Milestone at 12 months

BCR-ABL at 0.1% or lower. This is called a major molecular response (MMR). People who reach and keep MMR have a very low chance of CML getting worse.

Deep molecular response

BCR-ABL at 0.01% or lower (MR4) or 0.0032% or lower (MR4.5). This is needed before anyone can safely try stopping a TKI.

Undetectable BCR-ABL

No BCR-ABL found with a very sensitive test. Even then, a few CML cells usually remain, so you keep taking your TKI unless your care team plans a supervised stop.

Gene tests and what they mean

Every person with CML has the BCR-ABL gene. That is what makes TKIs work so well. The gene tests below help your care team confirm CML, follow your response, and pick the right TKI if one stops working.

Ask your care team to share your BCR-ABL results after each test. Many people keep a log of their numbers over time.

Philadelphia chromosome

The shortened chromosome 22 created when chromosomes 9 and 22 swap pieces. It is found in almost everyone with CML.

BCR-ABL fusion gene

The joined gene that drives CML. It is the target of all TKI pills.

Transcript type (e13a2 or e14a2)

The exact form of the BCR-ABL gene. Most people have one of these two common forms, and the lab needs to know which one to measure it. A rare form may need a special test.

International Scale (IS)

A standard way of reporting BCR-ABL results so they can be compared between labs. Try to use the same lab over time when possible.

Kinase domain mutations

Changes in the BCR-ABL gene that can make a TKI stop working. Different mutations respond to different TKIs.

T315I mutation

A specific change that makes imatinib, dasatinib, nilotinib, and bosutinib stop working. Ponatinib and asciminib can work against it.

Additional chromosome changes

Extra changes besides the Philadelphia chromosome, found on the marrow test. Some of them mean higher risk and closer follow-up.

Main treatments

For almost everyone with chronic phase CML, treatment is a TKI pill taken every day. There are several good choices. They all block BCR-ABL, but they differ in how fast they work, their side effects, how you take them, and their cost. Your care team will choose based on your risk score, other health problems, other medicines, and your preferences.

Taking your TKI every day, at the right time and in the right way, is the single most important thing you can do. Missing doses is one of the most common reasons CML stops responding.

Imatinib

The first TKI, taken once a day with food and a full glass of water. It has been used for more than 20 years and is now available as a lower-cost generic. It works well for many people, especially those with lower-risk CML.

Dasatinib

A second-generation TKI taken once a day, with or without food. It lowers BCR-ABL faster than imatinib. It can cause fluid around the lungs. Some acid-reducing medicines make it work less well.

Nilotinib

A second-generation TKI taken twice a day on an empty stomach. It lowers BCR-ABL faster than imatinib. It can raise blood sugar and cholesterol and can affect the heart and blood vessels, so it may not be the best choice for people with heart disease or diabetes.

Bosutinib

A second-generation TKI taken once a day with food. Diarrhea is common at first and often gets better. It can be used as a first treatment or after other TKIs.

Asciminib

A newer TKI that blocks BCR-ABL in a different spot (called a STAMP inhibitor). It is taken on an empty stomach. It is approved as a first treatment and for people whose CML did not respond to, or who could not take, other TKIs. It can also work against the T315I change. Many people have fewer side effects with it.

Ponatinib

A strong TKI used when other TKIs have not worked, or for the T315I change. It can raise the risk of blood clots, heart problems, and high blood pressure, so the dose is often lowered once CML responds.

Switching TKIs

If side effects are hard to live with, or BCR-ABL is not dropping as hoped, switching to another TKI often helps. Do not stop or change your pills on your own.

Treatment-free remission (stopping a TKI)

Some people with a deep, stable response can try stopping their TKI under close watch. This usually requires chronic phase CML, at least 3 years on a TKI, a deep response lasting at least 2 years, and a lab that can do very sensitive PCR tests. After stopping, you need BCR-ABL tests about monthly at first, then less often. About half of people stay in remission. If CML comes back, nearly everyone responds again when the TKI is restarted.

Stem cell transplant

A transplant using stem cells from a donor. It is rarely needed today. It may be used for blast phase or for CML that does not respond to several TKIs.

Clinical trials

Trials are testing new drugs and ways to help more people stop treatment safely. Ask your care team if one fits you.

Common side effects and what helps

Most TKI side effects are mild to moderate. Many are worst in the first few months and get better with time. Because you may take a TKI for years, it is important to tell your care team about side effects, even small ones. A dose change or a switch to another TKI can often help.

Many medicines, supplements, and foods interact with TKIs. Always tell your pharmacist and other doctors that you take one.

Fatigue

Feeling tired is common at first. Gentle daily activity, good sleep, and a steady routine help. Tell your care team if it does not improve.

Swelling and fluid

Imatinib can cause puffiness around the eyes and swelling in the legs. Dasatinib can cause fluid around the lungs (pleural effusion), which may cause shortness of breath or cough. Report new trouble breathing right away.

Muscle cramps and aches

Common with imatinib and some other TKIs. Staying hydrated and stretching can help. Your care team may check your minerals, like potassium and magnesium.

Nausea, diarrhea, and stomach upset

Taking imatinib or bosutinib with food can help. Diarrhea is common at the start of bosutinib and usually eases. Ask about medicines that can help.

Rash and skin changes

A rash or dry skin can happen. Gentle skin care and sun protection help. Tell your care team about any rash.

Low blood counts

In the first months, TKIs can lower white cells, red cells, or platelets. Your care team checks your counts and may pause the drug for a short time.

Heart, blood vessel, and blood sugar effects

Nilotinib and ponatinib can raise the risk of narrowed arteries, heart attack, stroke, and high blood sugar or cholesterol. Keep your blood pressure, cholesterol, and blood sugar well controlled, and do not smoke.

Liver and pancreas effects

Some TKIs can raise liver or pancreas blood tests. These are checked regularly.

TKI withdrawal symptoms

After stopping a TKI to try treatment-free remission, some people get muscle and joint aches for a few weeks or months. These usually fade and can be treated with simple pain relievers.

Pregnancy and fertility

TKIs can harm an unborn baby. Use reliable birth control during treatment. If you want to have a child, talk with your care team before trying, so you can plan safely together.

Living with CML

For most people, CML is a long-term condition managed with a daily pill and regular blood tests, much like other chronic illnesses. Many people work, travel, raise families, and live full lives.

Adherence means taking your TKI exactly as prescribed, every day. Use a pill box, phone alarm, or app, and link your dose to a daily habit. If cost, side effects, or busy days make it hard to take your pills, tell your care team. There is often help, such as lower-cost generics, copay programs, or a switch to another TKI.

Keep up with your BCR-ABL tests, even when you feel well. These tests catch problems early, long before you would feel anything. Ask for a copy of your results and keep track over time.

Take care of your heart and overall health: stay active, eat well, do not smoke, and keep up with regular checkups and cancer screenings. Support is available for you and your family. Groups like Blood Cancer United (formerly the Leukemia and Lymphoma Society) and the National CML Society offer free education and help.