Tests for Chronic Lymphocytic Leukemia (CLL)

Certain signs and symptoms or the results of blood tests (see below) might suggest that a person has chronic lymphocytic leukemia (CLL), but further tests are needed to be sure. If CLL is found, other tests will also be done to learn more about it.

Medical history and physical exam

If you might have CLL (or some other type of leukemia), your doctor will want to take a complete medical history, focusing on any symptoms you've had and how long you've had them. They might also ask about other health problems, as well as about possible risk factors for CLL.

During the physical exam, your doctor will pay close attention to your lymph nodes, abdomen (belly), and other areas that might be affected.

If there is reason to think you might have problems caused by low levels of blood cells (anemia, infections, bleeding or bruising, etc.), the doctor will most likely order tests to check your blood cell counts. If the results suggest leukemia, you may be referred to a hematologist, a doctor who specializes in treating blood disorders (including blood cancers like leukemia).

Blood tests

Most often, CLL can be diagnosed based on the results of blood tests (taken from a vein in the arm). Other blood tests might also be done to learn more about the leukemia and about a person's overall health.

Complete blood count and peripheral blood smear

The complete blood count (CBC) measures the amounts of red and white cells and platelets in your blood. This test is often done along with one that looks at the numbers of the different types of white blood cells (called a differential or diff). These tests are often the first ones done when a blood problem is suspected.

People with CLL have too many lymphocytes in their blood. (This is called lymphocytosis.) Having more than 5,000 lymphocytes/mm³ (per cubic millimeter) of blood strongly suggests CLL, but other tests are needed to know for sure. People with CLL might also have low levels of red blood cells and platelets.

For the peripheral blood smear, a sample of blood is looked at with a microscope. If you have CLL, the blood smear could show many abnormal looking lymphocytes called smudge cells.

Flow cytometry

This lab test is important in diagnosing CLL. It uses a machine that looks for certain substances (markers) on or in cells that help identify what types of cells they are.

Flow cytometry can be used to see if a sample of blood contains CLL cells. It can also be used to look for CLL cells in bone marrow or other fluids. (See below.) If a person has CLL, the test will show that the leukemia cells are all the same, and that they have certain markers.

Other blood tests

Blood chemistry tests may be done to measure the amount of certain chemicals in your blood, but they're not used to diagnose leukemia. In people already known to have CLL, these tests can help find liver or kidney problems caused by the spread of leukemia cells or certain chemotherapy (chemo) drugs. These tests also can check the levels of certain minerals so any imbalances can be treated.

Your doctor may order blood tests to check for previous hepatitis virus infections if you're going to be treated with a drug that might reactivate these infections. (You can find more on this in Immunotherapy for Chronic Lymphocytic Leukemia.)

Your blood immunoglobulin (antibody) levels may be tested to check if you have enough antibodies to fight infections, especially if you've recently had a lot of infections.

A blood protein called beta-2-microglobulin may be measured. High levels of this protein generally mean a more advanced CLL.

Lymph node biopsy

In a lymph node biopsy, all or part of a lymph node is removed so it can be looked at under a microscope and tested to see if it contains leukemia cells.

This test isn't always needed to diagnose CLL, but it might be done if the results of blood tests aren't enough to make the diagnosis. A lymph node biopsy may also be done if a lymph node has grown very large and the doctor wants to know if the leukemia has changed (transformed) into a more aggressive type of cancer.

Lymph node biopsies can be done in different ways.

In an excisional lymph node biopsy, an entire lymph node is removed through a cut in the skin. If the lymph node is very large, only part of it may be removed using an incisional biopsy. If the node is near the skin surface, this is a simple operation that can be done by first numbing the skin, but if the node is inside the chest or abdomen (belly), general anesthesia (where the patient is in a deep sleep) is used.

Less often, a needle biopsy may be done, either using a very thin, hollow needle (a fine needle aspiration, or FNA) or a slightly larger hollow needle (a core needle biopsy, or CNB). But it can be harder to diagnose CLL from a needle biopsy.

Bone marrow aspiration and biopsy

Blood tests or a lymph node biopsy are often enough to diagnose CLL, but if not, samples of bone marrow (the inner parts of certain bones, where new blood cells are made) might be tested.

A bone marrow aspiration and biopsy are usually done together. The samples of bone marrow are usually taken from the back of the pelvic (hip) bone, but sometimes they may be taken from other bones.

For a bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over your hip, the doctor uses a thin needle to put in a drug that numbs the area and the surface of the bone. This may cause brief stinging or burning. A hollow needle is then put into the bone, and a syringe is used to suck out a small amount of liquid bone marrow. Even with the numbing medicine, most people still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece (core) of bone and marrow is removed with a larger needle that's pushed down into the bone. Even with the numbing medicine, this can cause a feeling of pressure or tugging, but it usually doesn't hurt. After the biopsy is done, pressure will be put the site to help prevent bleeding.

Lab tests of blood and biopsy samples

Different types of lab tests might be done on blood or biopsy samples.

Routine microscopic exams

Samples from blood or biopsies are looked at under a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in cancer and blood diseases).

The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types.

A key factor is if the cells look mature (like normal blood cells that can fight infections). CLL cells tend to look mature, while cells of acute leukemias look immature.

Flow cytometry and immunohistochemistry

For both flow cytometry (as mentioned above) and immunohistochemistry (IHC), samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For IHC, the cells are then looked at with a microscope to see if the antibodies stuck to them (meaning they have these proteins), while for flow cytometry a special machine is used.

These tests are used for classifying leukemia cells according to the substances (antigens or markers) on their surfaces (a process called immunophenotyping). Leukemia cells can have different markers depending on which type of cells they start in and how mature they are, so this information can be helpful in diagnosing CLL or learning more about it.

Chromosome tests

Some tests look at the chromosomes inside the cells. Chromosomes are long strands of DNA that contain our genes. Normal human cells have 23 pairs of chromosomes, each of which are a certain size and look a certain way. CLL cells sometimes have chromosome changes that can be seen with a microscope or found with other tests. Recognizing these changes can be important in determining a person’s outlook and treatment options.

Cytogenetics (karyotyping): For this test, cells are grown in the lab for a couple of weeks, and then their chromosomes are examined under a microscope. Because it takes time for the cells to start dividing, this test usually takes 2 to 3 weeks to complete.

Fluorescent in situ hybridization (FISH): This test can be used to look at the cells’ chromosomes and DNA without having to grow the cells in the lab. It uses special fluorescent dyes that only attach to specific parts of particular chromosomes. FISH can be used to look for certain genes or chromosome changes (not just any change). 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.

What these tests look for

In people with CLL, the leukemia cells often have certain chromosome changes. For example, part of a chromosome may be missing. This is called a deletion. The most common deletions occur in parts of chromosomes 13, 11, or 17. Other, less common chromosome changes include an extra copy of chromosome 12 (trisomy 12) or a translocation (swapping of DNA) between chromosomes 11 and 14, written as t(11;14).

This type of information may be helpful to determine a person's prognosis (outlook). For example, the deletion of part of chromosome 13, written as del(13q14), is usually linked with a slower-growing disease and a better outlook, while a deletion of part of chromosome 17, written as del(17p), often means the leukemia is less likely to respond to certain kinds of treatment. But this information needs to be looked at along with other factors, such as the stage of the CLL.

Molecular and genetic tests

Other types of lab tests can also be done on the samples to look for specific gene or other changes in the leukemia cells. Some of the changes found on these tests can help doctors learn more about the leukemia, and some can even help tell if certain treatments are likely to be helpful. For example:

• Immunoglobulins, the antibodies that help your body fight infections, are made up of light chains and heavy chains. Whether the gene for the immunoglobulin heavy chain variable region (IGHV or IgV_H) has changed (mutated) can help your doctor know how aggressive your CLL is.
• TP53 is a gene that normally helps keep cells from growing out of control. Changes (mutations) in this gene tend to be linked with a poorer outlook, and they can affect which treatments are most likely to be helpful.

To learn more about these lab tests, see Tests Used on Biopsy and Cytology Samples to Diagnose and Classify Cancer.

Imaging tests

Imaging tests use x-rays, sound waves, or magnetic fields to create pictures of the inside of the body. Imaging tests are not done to diagnose CLL, but they may be done for other reasons, such as to look for the cause of symptoms such as chest pain or trouble breathing.

Computed tomography (CT) scan

A CT scan can show if any lymph nodes or organs in your body are enlarged. It may be done if your doctor suspects the leukemia is growing in an organ, like your spleen.

PET/CT scan

Some machines combine a CT scan with a PET scan (PET/CT scan). For a PET scan, glucose (a form of sugar) containing a radioactive atom is injected into the blood. Because cancer cells grow rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of the areas of radioactivity in the body. This test allows the doctor to compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT. This test might be used to guide a biopsy needle into a lymph node to remove a sample for testing.

Ultrasound

Ultrasound  uses sound waves and their echoes to make pictures of the inside of the body. It can be used to look at lymph nodes near the surface of the body or to look for enlarged organs (like the liver and spleen) inside your abdomen.