Chronic Myeloid Leukemia (CML)

What chronic myeloid leukemia is

The bone marrow makes three kinds of blood cells: red cells, platelets and white cells. In CML, a single blood stem cell acquires a gene change and starts producing too many granulocytes (a type of white cell called myeloid cells). Unlike acute myeloid leukemia, the cells in early CML still mature and work fairly normally. That is why the disease is "chronic" and can go unnoticed for months or years.

CML is one of the myeloproliferative neoplasms, the same family as polycythemia vera and myelofibrosis. It accounts for about 15% of adult leukemias. For an overview of all types, see leukemia.

The Philadelphia chromosome and BCR-ABL

Almost every case of CML carries the Philadelphia chromosome. Pieces of chromosomes 9 and 22 break off and swap places. The join creates a fusion gene called BCR-ABL1, which produces an enzyme (a tyrosine kinase) that is permanently switched on. It tells the cell to keep dividing. Modern CML drugs block this exact enzyme, which is why treatment works so well.

The change happens during a person's lifetime. It is not passed on to children, and family members do not have a higher risk. The only well-established risk factor is high-dose radiation exposure.

CML symptoms

Around half of people have no symptoms at diagnosis. The leukemia is found when a blood test done for another reason shows a high white count. When symptoms do occur, they usually build slowly:

• tiredness and pale skin from anemia
• a dragging feeling or fullness under the left ribs from an enlarged spleen, sometimes with getting full quickly after eating
• night sweats, low fever and unintended weight loss
• easy bruising or bleeding, or occasionally blood clots, because platelets may be very high or not work properly
• bone pain
• rarely, symptoms of very thick blood (leukostasis): headache, blurred vision, breathlessness or priapism

Phases of CML

CML is staged by phase rather than numbered stages. Phase is based on the proportion of immature cells (blasts) in the blood or marrow and on other features.

Before TKIs, chronic phase usually progressed to blast phase within a few years. Today, progression is uncommon in people who take their treatment and reach good responses.

How CML is diagnosed

1. Complete blood count (CBC): typically shows a high white count, often far above normal, with cells at every stage of maturity. Basophils and platelets are often raised.
2. Blood film: a specialist looks at the cells under a microscope.
3. Bone marrow biopsy: a sample from the back of the hip bone confirms the diagnosis, counts blasts and checks for extra chromosome changes.
4. Cytogenetics or FISH: detects the Philadelphia chromosome.
5. Quantitative PCR for BCR-ABL1: measures how much of the fusion gene is present. This number becomes the main marker used to track treatment for life.
6. Physical exam and sometimes ultrasound: to measure the spleen.

Your doctor may also calculate a risk score (such as Sokal or ELTS) from your age, spleen size and blood counts. It helps guide which TKI to start.

CML treatment

Tyrosine kinase inhibitors (TKIs)

TKIs are tablets that block the BCR-ABL enzyme. They are the standard first treatment in chronic phase:

• Imatinib: the first TKI, used since 2001, now available as a generic.
• Second-generation TKIs: dasatinib, nilotinib and bosutinib. They tend to produce faster, deeper responses.
• Later options: ponatinib, for resistance or the T315I mutation, and asciminib, which binds the enzyme at a different site.

The choice depends on your risk score, other health conditions and side-effect profile. Nilotinib, for example, is avoided with significant heart or blood vessel disease, and dasatinib can cause fluid around the lungs.

Common TKI side effects include tiredness, nausea, diarrhea, muscle cramps, rash, puffy eyes and low blood counts early on. Most are mild and ease over time. Some TKIs interact with grapefruit juice and with many common drugs, so check before taking new medicines or supplements.

Monitoring response

BCR-ABL1 levels are checked by PCR blood test every 3 months at first. Doctors look for set milestones:

• Major molecular response (MMR): BCR-ABL1 at 0.1% or less, ideally by 12 months.
• Deep molecular response: 0.01% or less, sometimes undetectable.

Not reaching milestones, or a rising level, prompts a check for adherence, drug interactions and resistance mutations, then a switch of TKI.

Stopping treatment (treatment-free remission)

Some people who have taken a TKI for several years and kept a deep molecular response for at least 2 years can try stopping under close supervision. About half stay in remission. Those who relapse almost always respond again when they restart the same drug. Never stop a TKI on your own.

Stem cell transplant and other treatment

An allogeneic stem cell transplant from a donor is the only treatment known to cure CML outright. Because of its risks, it is now reserved for people whose disease resists several TKIs or who are in blast phase. Blast phase is treated with chemotherapy like acute leukemia plus a TKI, aiming for transplant.

CML in pregnancy and children

TKIs can harm a developing baby. People who could become pregnant need effective contraception while taking them and should plan any pregnancy with their hematologist, who may pause treatment or switch to interferon. CML is rare in children, and TKIs can slow growth, so children are treated in specialist pediatric centers.

CML life expectancy and outlook

Before 2001, median survival was about 5 to 6 years. With TKIs, people diagnosed in chronic phase who respond well now have a life expectancy close to that of the general population. The best predictors are the phase at diagnosis and how quickly BCR-ABL1 falls in the first year. Taking the tablets every day matters: missed doses are a leading cause of losing response.

Frequently asked questions

Is chronic myeloid leukemia curable?

CML is not usually described as cured with tablets alone, but it is highly controllable. Most people on TKIs live a normal or near-normal lifespan. About half of those with a long, deep response can stop treatment and stay in remission. A donor stem cell transplant can cure it but carries serious risks.

What are the first symptoms of CML?

Often there are none, and a high white count is found on a routine blood test. When symptoms appear, the most common are tiredness, fullness or pain under the left ribs from a large spleen, night sweats, weight loss and easy bruising.

Is CML hereditary?

No. The Philadelphia chromosome develops in a single bone marrow cell during life. It is not present in the eggs or sperm, so it cannot be passed to children, and relatives do not need screening.

What is the difference between CML and CLL?

CML affects myeloid cells and is driven by BCR-ABL, which TKI tablets target. Chronic lymphocytic leukemia (CLL) affects lymphocytes, has different gene changes and different treatments. Both are slow-growing and often found on routine blood tests.

How long do you take CML medication?

Most people take a TKI for years and many for life. People who reach and hold a deep molecular response for several years may be offered a supervised trial of stopping, with monthly PCR tests at first so the drug can be restarted quickly if levels rise.

Can CML turn into acute leukemia?

Yes, if it is not controlled. Blast phase behaves like acute leukemia. This is now uncommon because TKIs keep most people in chronic phase, which is why regular PCR monitoring and taking every dose matter.