How is chronic myeloid leukemia diagnosed?
Many people with CML do not have symptoms when it is diagnosed. The leukemia is often found when their doctor orders blood tests for an unrelated health problem or during a routine checkup. Even when symptoms are present, they are often vague and non-specific.
Types of samples used to test for chronic myeloid leukemia
If signs and symptoms suggest you may have leukemia, the doctor will need to check samples (specimens) of blood and bone marrow to be certain of this diagnosis. Other tissue and cell samples may also be taken in order to treat CML.
Blood samples for tests for CML are generally taken from a vein in the arm.
Bone marrow samples
Bone marrow samples are taken from a bone marrow aspiration and biopsy. These 2 tests are usually done at the same time. The samples are taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the breastbone (sternum) or other bones.
For a bone marrow aspiration, you lie on a table (either on your side or on your belly). After the area is cleaned, the skin over the hip and the surface of the bone is numbed with local anesthetic, which may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount (about 1 teaspoon) of liquid bone marrow. Even with the anesthetic, most patients still feel some brief pain when the marrow is removed.
A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow (about 1/16 inch in diameter and 1/2 inch long) is removed with a slightly larger needle that is twisted as it is pushed down into the bone. The biopsy may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.
These samples are sent to a lab, and they are looked at under a microscope for leukemia cells. These tests may also be done after treatment to see if the leukemia is responding to treatment.
One or more of the following lab tests may be used to diagnose CML or to help determine how advanced the disease is.
Blood cell counts and blood cell exam
The complete blood count (CBC) is a test that measures the levels of different cells, like red blood cells, white blood cells, and platelets, in the blood. The CBC often includes a differential (diff), which is a count of the different types of white blood cells in the blood sample. In a blood smear, some of the blood is put on a slide to see how the cells look under the microscope. Most patients with CML have too many white blood cells with many early (immature) cells. Sometimes CML patients have low numbers of red blood cells or blood platelets. Even though these findings may suggest leukemia, this diagnosis usually needs to be confirmed by another blood test or a test of the bone marrow.
Blood chemistry tests
These tests measure the amount of certain chemicals in the blood, but they are 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 chemotherapy drugs. These tests also help determine if treatment is needed to correct low or high blood levels of certain minerals.
Routine exam under a microscope
The samples of blood and bone marrow are looked at under a microscope by a pathologist (a doctor who specializes in diagnosing diseases with lab tests) and may be looked at by a hematologist/oncologist (a doctor specializing in treating blood diseases and cancer) as well.
The doctors will look at the size and shape of the cells in the samples and whether they contain granules (small spots seen in some types of white blood cells).
An important factor is whether the cells look mature (like normal circulating blood cells) or immature (lacking features of normal circulating blood cells). The most immature cells are called myeloblasts (often called blasts).
An important feature of a bone marrow sample is how much of it is blood-forming cells. This is known as cellularity. Normal bone marrow contains both blood-forming cells and fat cells. When the bone marrow has more blood-forming cells than expected, it is 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 hypercellular because it is full of leukemia cells.
Some sort of gene testing will 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.
Conventional cytogenetics: This test looks at chromosomes (pieces of DNA) under a microscope to find any changes. It is also called karyotyping. Chromosomes in a cell can best be seen when the cell is dividing. That is why to do this test, a sample of blood or bone marrow has to be cultured (in the lab) so that the cells start to grow and divide. This takes time, and is not always successful. Normal human cells have 23 pairs of chromosomes, each of which is a certain size. The leukemia cells in many CML patients contain an abnormal chromosome known as the Philadelphia chromosome, which looks like a short chromosome 22. It is caused by swapping pieces (translocation) between chromosomes 9 and 22 (see the section, "Do we know what causes chronic myeloid leukemia?"). Finding a Philadelphia chromosome is helpful in diagnosing CML. Even when the Philadelphia chromosome can't be seen, other tests can often find the BCR-ABL gene.
Fluorescent in situ hybridization: Fluorescent in situ hybridization (FISH) is another way to look at chromosomes. This test uses special fluorescent dyes that only attach to specific parts of genes or chromosomes. FISH can be used to look for specific pieces of the BCR-ABL gene on chromosomes. It can be used on regular blood or bone marrow samples without culturing the cells first, so the results can come back quicker than with conventional cytogenetics.
Polymerase chain reaction (PCR): This is a super-sensitive test that can be used to look for the BCR-ABL oncogene in leukemia cells. It can be done on blood or bone marrow samples and can detect very small amounts of BCR-ABL, even when doctors can't find the Philadelphia chromosome in bone marrow cells with cytogenetic testing. PCR can be used to help diagnose CML and is also useful after treatment to see if copies of the BCR-ABL gene are still there. If copies of this gene are still present it means that the leukemia is still present, even when the cells aren't visible under the microscope.
Imaging tests produce pictures of the inside of the body. There are several imaging tests that might be done in people with leukemia. Leukemia does not usually form visible tumors, so imaging tests are not often helpful in making the diagnosis but they may be done to help find the extent of the disease.
Computed tomography scan
This test can help tell if any lymph nodes or organs in your body are enlarged. It isn’t usually needed to diagnose CML, but it may be done if your doctor suspects the leukemia is growing in an organ, like your spleen.
The computed tomography (CT) scan is a type of x-ray test that produces detailed, cross-sectional images of your body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs). A CT scanner has been described as a large donut, with a narrow table in the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.
Instead of taking one picture like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into detailed images of the part of your body that is being studied.
Often before the test, you may be asked to drink a contrast solution that helps better outline abnormal areas in the body. This helps outline abnormal areas more clearly. You may also receive an IV (intravenous) line through which a different contrast dye (IV contrast) is injected. This also helps outline abnormal areas.
The IV injection of contrast dye can cause some flushing (redness and a feeling of warmth in the face or elsewhere). Some people are allergic to the dye and get hives. Rarely, more serious reactions like trouble breathing and low blood pressure can occur. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.
In some cases, a CT can be used to guide a biopsy needle precisely into a suspected abnormality, such as an abscess. For this procedure, called a CT-guided needle biopsy, you remain on the CT scanning table while a radiologist moves a biopsy needle through the skin and toward the location of the mass. CT scans are repeated until the needle is within the mass. A sample is then removed to be looked at under a microscope. This is rarely needed in CML.
Magnetic resonance imaging scan
Magnetic resonance imaging (MRI) scans are very helpful in looking at the brain and spinal cord. These scans can also be used to look at other areas of the body. MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. Not only does this create images of cross-sectional slices of the body like a CT scanner, it can also produce images of slices that are parallel with the length of your body.
A contrast material might be injected, just as with CT scans, but this is done less often. This will be a different contrast from that used for CT scans, so being allergic to one doesn’t mean you are allergic to the other.
MRI scans take longer than CT scans, often up to an hour. You might have to lie inside a narrow tube, which is confining and can upset people with a fear of enclosed spaces. Special, "open" MRI machines may help with this problem. The MRI machine makes loud buzzing noises that you may find disturbing. Some places give you headphones or earplugs to help block this noise out.
Ultrasound uses sound waves and their echoes to make a picture of internal organs or masses. Most often for this test a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with a gel). It gives off sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image that is shown on a computer screen.
Ultrasound can be used to look at lymph nodes near the surface of the body or to look for enlarged organs inside your abdomen such as the kidneys, liver, and spleen.
This is an easy test to have, and it doesn't use radiation. For most scans you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.
A plain x-ray of your chest can be done in most outpatient settings. In patients with CML, it isn't needed for a diagnosis, but an x-ray may be used to see if you have normal lungs or if you have an infection.
Last Medical Review: 09/23/2013
Last Revised: 02/10/2014