Tests for Chronic Lymphocytic Leukemia (CLL)

If signs and symptoms or the results of blood tests suggest you might have chronic lymphocytic leukemia (CLL), 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 another type of leukemia), your health care team will most likely do a physical exam and take a complete medical history.

During the medical history, they will focus on any symptoms you've had and how long you've had them. They might also ask about other health problems, as well as possible risk factors for CLL.

During the physical exam, they 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.), your health care team will likely order tests to check your blood cell counts.

If the results suggest leukemia, you will probably be referred to a hematologist/oncologist—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 your arm). Other blood tests might also be done to learn more about the leukemia and your overall health.

Complete blood count and peripheral blood smear

A complete blood count (CBC) measures the amounts of red and white blood cells and platelets in your blood. This test is often done along with a differential (or “diff”), which is a count of the different types of white blood cells in the blood sample.  

These tests are often the first ones done when a blood problem is suspected.

People with CLL have too many lymphocytes, a type of white blood cell, 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 for diagnosing CLL. It is described in more detail below.

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 by certain chemotherapy (chemo) drugs.
• These tests can also 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.

More information on this can be found 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 (B2M) 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 for leukemia cells. This test isn't always needed to diagnose CLL, but it might be done if blood tests results 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 transformed into a more aggressive type of cancer.

Lymph node biopsies can be done in different ways.

Excisional or incisional biopsy

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 often a simple operation that can be done by first numbing your skin. But if the node is inside your chest or abdomen (belly), general anesthesia (where you are put into a deep sleep) is used.

Needle biopsy

Less often, a needle biopsy may be done using 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 your bone marrow might be tested. Bone marrow is the inner part of certain bones, where new blood cells are made.

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

Bone marrow aspiration

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 small 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 through the hard part of the bone into the soft marrow, 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.

Bone marrow biopsy

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 is pushed into your bone.

Even with numbing medicine, this can still sometimes hurt. After the biopsy, pressure will be put on the site to help prevent bleeding.

Lab tests of blood and biopsy samples

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

Routine microscopic exams

Samples from blood or biopsies are looked at under a microscope by a pathologist (a doctor who specializes in looking at lab tests and biopsy samples). The samples may also be reviewed by your 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

Flow cytometry and immunohistochemistry (IHC) are tests used to classify leukemia cells according to the substances (antigens or markers) on their surfaces. This process is 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.

In both tests, samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on the surface of cells.

• For IHC, the treated cells are then looked at with a microscope to see if the antibodies stuck to them (meaning they have these proteins).
• Flow cytometry classifies the treated cells using a special machine.

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 your outlook and treatment options.

Cytogenetics (karyotyping): For this test, cells are grown in the lab for at least several days, 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 certain chromosomes.

FISH can be used to look for certain specific 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 chromosome 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 your 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 your CLL.

Molecular and genetic tests

Other types of lab tests can also be done on the samples to look for specific gene changes or other changes in the leukemia cells.

Some of the changes found on these tests can help your cancer care team learn more about your leukemia. Some can even help them understand if certain treatments are likely to be helpful.

For example:

• Immunoglobulins are the antibodies that help your body fight infections. They are made up of light chains and heavy chains. Your doctor can get an idea of how aggressive your CLL is likely to be by looking at if the gene for the immunoglobulin heavy chain variable region (IGHV or IgV_H) has changed (mutated).
• 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.

Newer types of lab tests can look for multiple gene mutations at the same time. These are known as next generation sequencing (NGS) tests.

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 your 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 like chest pain, weight loss, or trouble breathing.

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 lymph nodes or 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.

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 your 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 your body.

This test allows the doctor to compare areas of higher radioactivity on the PET scan with more detailed images from the CT scan. For example, 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 your body. It can be used to look at lymph nodes near the surface of your body or to look for enlarged organs (like the liver and spleen) inside your abdomen.