Tests for Chronic Myeloid Leukemia (CML)

If signs and symptoms or the results of blood tests suggest you might have chronic myeloid leukemia (CML), your health care team will do further tests to be sure.

If CML is found, other tests will also be done to learn more about it.

Medical history and physical exam

If your health care team thinks you might have CML (or another type of leukemia), they will most likely do a physical exam and take a complete medical history.

• During the medical history, they will focus on any symptoms and how long you've had them. They’ll also ask you about any other health problems.
• During the physical exam, they will pay close attention to your abdomen (belly), especially your spleen (which is on the left side under your ribs) and other parts of your body that might be affected.

If there is reason to think you might have problems caused by low levels of blood cells (tiredness, infections, bleeding or bruising, etc.), your health care team will likely order tests to check your blood cell counts (see below).

If the results suggest leukemia, you will probably be referred to a hematologist/oncologist. This is a doctor who specializes in treating blood disorders, including blood cancers like leukemia.

Blood and bone marrow tests

If your doctor thinks you might have leukemia, they will need to check your blood and bone marrow to be sure.

• Blood is usually taken from a vein in your arm.
• A small amount of bone marrow is removed with a bone marrow aspiration and biopsy.

These samples are sent to a lab, where they're checked under a microscope. They might also have other types of tests done on them.

Blood cell counts

• Complete blood cell count (CBC): The CBC measures the levels of different cells in your blood (red blood cells, white blood cells, and platelets). It often includes a differential (diff), which is a count of the different types of white blood cells in your blood sample.
• Blood smear: In a blood smear, some of your blood is put on a slide to see how the cells look under the microscope.

These are often the first tests done when doctors suspect a blood problem.

What doctors look for on these tests

Most people with CML have too many white blood cells (leukocytosis), with a lot of early (immature) cells, including very early cells called myeloblasts or blasts.

With these tests, doctors look at:

• The size and shape of the white blood cells
• Whether they contain granules (small spots seen in some types of white blood cells)
• Whether the cells look mature (like normal circulating blood cells) or immature (lacking features of normal circulating blood cells)

Sometimes people with CML have low numbers of red blood cells or blood platelets. Even though these findings may suggest leukemia, the diagnosis typically needs to be confirmed with other tests.

Bone marrow samples

Leukemia starts in the bone marrow, so checking your bone marrow for leukemia cells is often a key part of testing for it. Bone marrow samples are collected during a bone marrow aspiration and biopsy.

These 2 tests are usually done at the same time.

The samples are usually taken from the back of your pelvic (hip) bone, but sometimes other bones are used instead. If only an aspiration is done, it may be taken from your sternum (breastbone).

Bone marrow aspiration

For a bone marrow aspiration, you lie on a table (either on your side or on your belly). The doctor cleans the skin over your hip and then numbs the area and the surface of the bone by injecting a local anesthetic. This may cause a brief stinging or burning sensation.

A thin, hollow needle is then inserted into your bone, and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most people still have some brief pain when the marrow is removed.

Bone marrow biopsy

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into your bone. This may also cause some brief pain. Once the biopsy is done, pressure is applied to the site to help prevent bleeding.

What doctors look for on these tests

Doctors will look at how much of the bone marrow sample is made up of blood-forming cells. This is known as cellularity. Normal bone marrow contains both blood-forming cells and fat cells.

• If your bone marrow has more blood-forming cells than expected, it's said to be hypercellular.
• If too few of these cells are found, the marrow is called hypocellular.

In people with CML, the bone marrow is often very hypercellular because it's full of leukemia cells.

These tests may also be done once treatment is started to see how well the leukemia is responding to treatment.

Blood chemistry tests

Blood chemistry tests measure the amount of certain chemicals in your blood, but they're not used to diagnose leukemia.

They can help find liver or kidney problems caused by the spread of leukemia cells or by the side effects of certain drugs. These tests can also help determine if you need to be treated to correct low or high blood levels of certain minerals.

Gene and chromosome tests

CML is diagnosed when tests show a person has the abnormal BCR::ABL1 gene (also known as BCR-ABL) or the Philadelphia chromosome in their leukemia cells.

(The Philadelphia chromosome contains the BCR::ABL1 gene. For more on these genetic changes, see What Causes Chronic Myeloid Leukemia?).

Some sort of gene testing will be done to look for the Philadelphia chromosome and/or the BCR::ABL1 gene. This type of testing is used to confirm a CML diagnosis and learn more about your CML cells.

Cytogenetics (karyotyping)

This test looks for changes in the chromosomes (long strands of DNA) inside cells under a microscope.

In people who might have CML, the test is used to look for the Philadelphia chromosome (an abnormally short chromosome 22). The Philadelphia chromosome is found in the leukemia cells of almost all people with CML.

Cytogenetic testing might also find other chromosome changes in the cells. This is more common if the CML is progressing to a more advanced phase.

This test usually takes 2 to 3 weeks to complete, because chromosomes can best be seen when the cell is dividing. A sample of your blood or bone marrow must be grown in the lab for at least several days, until the cells start to divide.

Fluorescent in situ hybridization (FISH)

FISH testing is used to look for specific genes or chromosome changes (not just any change) in cells from a blood or bone marrow sample.

This test lets doctors look at chromosomes and DNA without first having to grow the cells in the lab. It uses special fluorescent dyes that only attach to specific parts of certain chromosomes. Because the cells don’t have to grow in the lab first, the results are usually available faster than with cytogenetics, often within a few days.

In people who might have CML, FISH can look for specific pieces of the BCR::ABL1 gene. It can often find the BCR::ABL1 gene even if cytogenetics doesn’t find the Philadelphia chromosome, or if cytogenetic testing can’t be done for some reason.

Polymerase chain reaction (PCR)

This very sensitive test can look for signs of the BCR::ABL1 gene (in the form of RNA) in leukemia cells. It is also known as reverse transcriptase polymerase chain reaction (RT-PCR).

PCR is done on blood or bone marrow samples. It can detect very small amounts of BCR::ABL1, even when doctors can't find the Philadelphia chromosome in bone marrow cells with cytogenetic testing.

Quantitative PCR (qPCR) during treatment

PCR can also be useful during treatment for CML, to check the level of BCR::ABL1 gene products (and therefore leukemia cells) still in the blood or bone marrow.

This is known as quantitative PCR (qPCR).

The level is typically given as a percentage based on the International Scale (IS). The percentage should go down over time if treatment is working, so the IS can help doctors see how you are responding to treatment.

(For more on this, see How Do You Know If Treatment for Chronic Myeloid Leukemia Is Working?)

Imaging tests

Imaging tests use x-rays, sound waves, or magnetic fields to create pictures of the inside of your body. They aren't needed to diagnose CML, but they might be used to look for the cause of symptoms or to see if organs like your spleen or liver are enlarged.

Computed tomography (CT) scan

A CT scan uses x-rays to make detailed images of the inside of your body. It can show if any organs in your body are enlarged. It may be done if your cancer care team suspects the leukemia is growing in an organ, like your spleen.

Magnetic resonance imaging (MRI)

Like CT scans, MRIs make detailed images of soft tissues in your body. But MRI scans use radio waves and strong magnets instead of x-rays. MRIs are very helpful in looking at the brain and spinal cord, but they aren’t usually needed in people with CML.

Ultrasound

Ultrasound uses sound waves and their echoes to make pictures of internal organs. It can be used to look for enlarged organs inside your abdomen (belly) such as your liver and spleen.