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chronic-lymphocytic-leukaemia

Leukemia - Chronic Lymphocytic (CLL)

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What is chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) is a type of cancer that starts from white blood cells (called lymphocytes) in the bone marrow. It then invades the blood. Leukemia cells tend to build up in the body over time, but in many cases people don't have any symptoms for at least a few years. In time, it can also invade other parts of the body, including the lymph nodes, liver, and spleen. Compared to other types of leukemia, CLL usually grows slowly.

Doctors have found that there seem to be 2 different kinds of CLL:

One kind of CLL grows very slowly and rarely needs to be treated. People with this kind of CLL survive an average of 15 years or more.

The other kind of CLL grows faster and is a more serious disease. People with this form of CLL survive an average of about 8 years.

The leukemia cells from these 2 types look alike, but lab tests can tell the difference between them. The tests look for proteins called ZAP-70 and CD38. Patients whose CLL cells contain low amounts of ZAP-70 and CD38 have a better prognosis (outlook).

Leukemia is different from other types of cancer that start in organs like the lungs, colon, or breast and then spread to the bone marrow. Cancers that start elsewhere and then spread to the bone marrow are not leukemia.

Normal bone marrow, blood, and lymphoid tissue

To understand the different types of leukemia, it helps to know some basic facts about the blood and lymph systems.

Bone marrow

Bone marrow is the soft inner part of some bones such as the skull, shoulder blades, ribs, pelvis, and backbones. The bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow.

Blood stem cells go through a series of changes to make new blood cells. During this process, the cells develop into either lymphocytes (a kind of white blood cell) or other blood-forming cells. The blood-forming cells can develop into 1 of the 3 main types of blood cell components:

Red blood cells

White blood cells (other than lymphocytes)

Platelets

Red blood cells

Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed. Anemia (having too few red blood cells in the body) typically causes a person to feel tired, weak, and short of breath because the body tissues are not getting enough oxygen.

Platelets

Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in plugging up holes in blood vessels caused by cuts or bruises. A shortage of platelets is calledthrombocytopenia. A person with thrombocytopenia may bleed and bruise easily.

White blood cells

White blood cells help the body fight infections. Lymphocytes are one type of white blood cell. The other types of white blood cells are granulocytes (neutrophils, basophils, and eosinophils) and monocytes.

Lymphocytes: These are the main cells that make up lymphoid tissue, a major part of the immune system. Lymphoid tissue is found in lymph nodes, the thymus gland, the spleen, the tonsils and adenoids, and is scattered throughout the digestive and respiratory systems and the bone marrow.

Lymphocytes develop from cells called lymphoblasts to become mature, infection-fighting cells. The 2 main types of lymphocytes are known as B lymphocytes (B cells) and T lymphocytes (T cells).

B lymphocytes protect the body from invading germs by developing (maturing) into plasma cells, which make proteins called antibodies. The antibodies attach to the germs (bacteria, viruses, and fungi), which helps other white blood cells called granulocytes to recognize and destroy them. B lymphocytes are the cells that most often develop into chronic lymphocytic leukemia (CLL) cells.

T lymphocytes can recognize cells infected by viruses and directly destroy these cells.

Granulocytes: These are white blood cells that have granules in them. Granules are spots that can be seen under the microscope. They contain enzymes and other substances that can destroy germs, such as bacteria. The 3 types of granulocytes -- neutrophils, basophils, and eosinophils -- are distinguished by the size and color of their granules. Granulocytes develop from blood-forming cells called myeloblasts to become mature, infection-fighting cells.

Monocytes: These white blood cells, which are related to granulocytes, also are important in protecting the body against bacteria. They start in the bone marrow as blood-forming monoblasts and develop into mature monocytes. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them. Macrophages also help lymphocytes recognize germs and start making antibodies to fight them.

Any of the blood-forming or lymphoid cells from the bone marrow can turn into a leukemia cell. Once this change takes place, the leukemia cells fail to go through their normal process of maturing. Most leukemia cells may reproduce quickly, but often the problem is that they don't die when they should. They survive and build up in the bone marrow. Over time, these cells spill into the bloodstream and spread to other organs, where they can prevent other cells in the body from functioning normally.

Types of leukemia

Not all leukemias are the same. Leukemias are divided into 4 main types. Knowing the specific type of leukemia helps doctors better predict each patient's prognosis (outlook) and select the best treatment.

Acute leukemia versus chronic leukemia

The first factor in classifying leukemia is whether most of the abnormal cells are mature (look like normal white blood cells) or immature (look more like stem cells).

In acute leukemia, the bone marrow cells cannot mature properly. Immature leukemia cells continue to reproduce and build up. Without treatment, most patients with acute leukemia would live only a few months. Some types of acute leukemia respond well to treatment, and many patients can be cured. Other types of acute leukemia have a less favorable outlook.

In chronic leukemia, the cells can mature partly but not completely. These cells may look fairly normal, but they are not. They generally do not fight infection as well as normal white blood cells do. And they survive longer, build up, and crowd out normal cells. Chronic leukemias tend to develop over a longer period of time, and most patients can live for many years. But chronic leukemias are generally harder to cure than acute leukemias.

Myeloid leukemia versus lymphocytic leukemia

The second factor in classifying leukemia is the type of bone marrow cells that are affected.

Leukemias that start in early forms of myeloid cells -- white blood cells (other than lymphocytes), red blood cells, or platelet-making cells (megakaryocytes) -- are myeloid leukemias (also known as myelocytic, myelogenous, or non-lymphocytic leukemias).

If the cancer starts in lymphocytes, it is called lymphocytic leukemia (also known as lymphoid or lymphoblastic leukemia). Lymphomas are also cancers that start in lymphocytes. While lymphocytic leukemias develop from cells in the bone marrow, lymphomas develop from cells in lymph nodes or other organs.

By considering whether leukemias are acute or chronic, and whether they are myeloid or lymphocytic, they can be divided into 4 main types:

Acute myeloid (or myelogenous) leukemia (AML)

Chronic myeloid (or myelogenous) leukemia (CML)

Acute lymphocytic (or lymphoblastic) leukemia (ALL)

Chronic lymphocytic leukemia (CLL)

Rarer forms of lymphocytic leukemia

There is the common form of CLL (which starts in B lymphocytes), but there are some rare types of leukemia that share some features with CLL.

Prolymphocytic leukemia (PLL): This is a type of leukemia in which the cancer cells are similar to normal cells called prolymphocytes -- immature forms of B lymphocytes (B-PLL) or T lymphocytes (T-PLL). Both B-PLL and T-PLL tend to be more aggressive than the usual type of CLL. Most cases will respond to some form of treatment, but over time they tend to relapse. PLL may develop in someone who already has CLL (in which case it tends to be more aggressive), but it can also occur in people who have never had CLL.

Large granular lymphocyte (LGL) leukemia: This is another rare form of chronic leukemia. The cancer cells are large and have features of either T lymphocytes or natural killer (NK) cells (another type of lymphocyte). Most LGL leukemias are slow-growing, but a small number are more aggressive. Drugs that suppress the immune system may be helpful, but aggressive cases are very hard to treat.

Hairy cell leukemia (HCL): This is another cancer of lymphocytes that tends to progress slowly. It accounts for about 2% of all leukemias. The cancer cells are a type of B lymphocyte but are different from those seen in CLL. There are also important differences in symptoms and treatment. This type of leukemia gets its name from the way the cells look under the microscope -- they have fine projections on their surface that make them look "hairy." 

What are the risk factors for chronic lymphocytic leukemia?

A risk factor is something that affects a person's chance of getting a disease like cancer. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for a number of cancers.

But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And many people who get the disease may not have had any known risk factors. Even if a person has a risk factor and develops cancer, it is often very hard to know how much that risk factor may have contributed to the cancer.

There are very few known risk factors for chronic lymphocytic leukemia (CLL).

Certain chemical exposures

Some studies have linked exposure to Agent Orange, an herbicide used during the Vietnam War, to an increased risk of CLL. Some other studies have suggested that farming and long-term exposure to some pesticides may be linked to an increased risk of CLL, but more research in this area is needed.

Family history

First-degree relatives (parents, siblings, or children) of CLL patients have a 2- to 4-fold increased risk for this cancer.

Gender

CLL is slightly more common in males than females, but the reasons for this are not known.

Do we know what causes chronic lymphocytic leukemia?

The exact cause of most cases of chronic lymphocytic leukemia (CLL) is not known. But scientists have learned a great deal about the differences between normal lymphocytes and CLL cells in recent years.

Normal human cells grow and function based mainly on the information contained in each cell's chromosomes. Chromosomes are long molecules of DNA in each cell. DNA is the chemical that carries our genes -- the instructions for how our cells function. We resemble our parents because they are the source of our DNA. But our genes affect more than the way we look.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA.

Some genes contain instructions for controlling when our cells grow and divide. Certain genes that promote cell growth and division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are calledtumor suppressor genes. Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes.

Each human cell contains 23 pairs of chromosomes. In most cases of CLL, a change can be found in at least one of these chromosomes. Most often this change is a deletion -- that is, loss of part of a chromosome. The loss of part of chromosome 13 is the most common deletion, but other chromosomes such as 11 and 17 can also be affected. Sometimes there is an extra chromosome 12 (trisomy 12). Other, less common abnormalities may also be found. Scientists know these chromosome changes are important in CLL, but it's not yet clear which genes they involve or exactly how they lead to leukemia.

We do know that normal B lymphocytes are part of the immune system. They are programmed to grow and divide when they come into contact with a foreign substance called an antigen. (Scientists call substances foreign if they don't normally occur in a person's body and can be recognized by their immune system. Germs contain foreign antigens. So do blood cells from someone else with a different blood type.) Scientists think that CLL begins when B lymphocytes continue to divide without restraint after they have reacted to an antigen. But why this happens is not yet known.

Sometimes people inherit DNA mutations from a parent that greatly increase their risk of getting certain types of cancer. But inherited mutations rarely cause CLL. DNA changes related to CLL usually occur during the person's lifetime, rather than having been inherited before birth.

Can chronic lymphocytic leukemia be prevented?

Many types of cancer can be prevented by lifestyle changes to avoid certain risk factors, but there are very few known risk factors for chronic lymphocytic leukemia (CLL), and most of these cannot be avoided. Most CLL patients have no known risk factors, so there is no way to prevent these cancers.

Can chronic lymphocytic leukemia be found early?

The American Cancer Society recommends screening tests for certain cancers in people without any symptoms, because they are easier to treat if found early. But at this time, no screening tests are routinely recommended to detect chronic lymphocytic leukemia (CLL) early.

CLL is sometimes found on routine blood tests done for other reasons. For instance, a person's white blood cell count may be very high, even though he or she doesn't have any symptoms.

It is important to report any symptoms that could be caused by CLL to the doctor right away.

How is chronic lymphocytic leukemia diagnosed?

Certain signs and symptoms might suggest that a person has chronic lymphocytic leukemia (CLL), but tests are needed to confirm the diagnosis.

Many people with CLL do not have any symptoms when it is diagnosed. The leukemia is often found when their doctor orders blood tests for some unrelated health problem or during a routine checkup.

Signs and symptoms

Even when people with CLL have symptoms, they are often vague and non-specific. Symptoms can include the following:

Weakness

Feeling tired

Weight loss

Fever

Night sweats

Enlarged lymph nodes (felt as lumps under the skin)

Pain or a sense of "fullness" in the belly (especially after eating a small meal), which is caused by an enlarged spleen

Many of the signs and symptoms of advanced CLL occur because the leukemia cells replace the bone marrow's normal blood-making cells. As a result, people do not make enough red blood cells, properly functioning white blood cells, and blood platelets.

Anemia is a shortage of red blood cells. It can cause tiredness, weakness, and shortness of breath.

A shortage of normal white blood cells (leukopenia) increases the risk of infections. A common term you may hear is neutropenia, which refers specifically to low levels of neutrophils (a type of granulocyte). Patients with CLL may have very high white blood cell counts because of excess numbers of lymphocytes (lymphocytosis), but the leukemia cells do not protect against infection the way normal white blood cells do.

A shortage of blood platelets (thrombocytopenia) can lead to excess bruising, bleeding, frequent or severe nosebleeds, and bleeding gums.

People with CLL have a higher risk of infections. This is mainly because their immune systems are not working as well as they should. CLL is a cancer of B lymphocytes, which normally make antibodies that help fight infection. But in CLL, these antibody-making cells don't work as they should, so they can't fight infections well. Infections may range from simple things like frequent colds or cold sores to pneumonia and other serious infections.

CLL may also affect the immune system in other ways. In some people with CLL, the immune system cells make abnormal antibodies that attack normal blood cells. This is known as autoimmunity. It can lead to low blood counts. If the antibodies attack red blood cells, it is known as autoimmune hemolytic anemia. Less often, the antibodies attack platelets and the cells that make them, leading to low platelet counts (thrombocytopenia). Rarely, the antibodies attack white blood cells, leading to leukopenia (low white blood cell counts).

CLL often causes the liver or spleen to become enlarged. If these organs are enlarged, you may notice fullness or swelling of the belly. You may also notice that you feel full after only a small meal. The spleen is on the left side, while the liver is on the right. These organs are usually covered by the lower ribs but when they are larger than normal your doctor can feel them.

CLL will often invade the lymph nodes. If the nodes are close to the surface of the body (for instance, on the sides of the neck, in the groin, in the underarm area, or above the collarbone), you or your doctor may notice the swelling as a lump under the skin. Lymph nodes inside the chest or abdomen may also become swollen, but these can be found only by imaging tests such as a computed tomography (CT) scan.

The symptoms and signs above may be caused by CLL, but they can also be caused by other conditions. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed.

Medical history and physical exam

If you have any signs or symptoms that suggest you might have leukemia, your doctor will want to take a complete medical history to check for symptoms and possible risk factors. You will also be asked about your general health.

A physical exam provides information about your general health, possible signs of leukemia, and other health problems. During the physical exam, your doctor will pay close attention to your lymph nodes and other areas that might be affected.

Types of samples used to test for chronic lymphocytic leukemia

If symptoms and/or the results of the physical exam suggest you may have leukemia, the doctor will need to check samples of blood and bone marrow to be certain of this diagnosis. Other tissue and cell samples may also be taken to help guide treatment.

Blood samples

Blood samples for tests for CLL are generally taken from a vein in the arm.

Bone marrow samples

Bone marrow samples are obtained from a bone marrow aspiration and biopsy, usually at the same time. The samples are usually taken from the back of the pelvic (hip) bone, but sometimes they may be taken from the sternum (breastbone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the area and the surface of the bone 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 of liquid bone marrow (about 1 teaspoon). Even with the anesthetic, most patients still have 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 tests are not usually needed to diagnose CLL, but they may help tell how advanced it is. They are often done before starting treatment to see how much CLL is in the bone marrow. They may then be repeated during or after treatment to see if the treatment is effective.

Lymph nodes

In an excisional lymph node biopsy, an entire lymph node is removed through a cut in the skin. If the node is near the skin surface, this is a simple operation that can be done with local anesthesia, but if the node is inside the chest or abdomen, general anesthesia (where the patient is asleep) is used.

This type of biopsy is often used to diagnose lymphomas, but it is only rarely needed in CLL. It may be used if a lymph node has grown very large and the doctor wants to know if the leukemia has changed (transformed) into a more aggressive lymphoma.

Spinal fluid

The procedure used to take samples of spinal fluid (also called cerebrospinal fluid or CSF) is called a lumbar puncture (or spinal tap). CSF is the liquid that surrounds the brain and spinal cord. For this test, the doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.

This is not a routine test for patients with CLL. It is only done if the doctor suspects leukemia cells may have spread to the area around the brain or spinal cord (which is rare), or if there might be an infection in those areas.

Lab tests used to diagnose and classify leukemia

One or more of the following lab tests may be done on the samples to diagnose CLL or to help determine how advanced the disease is.

Complete blood count and blood cell exam (peripheral blood smear)

The complete blood count (CBC) is a test that measures the different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. This test is often done along with a differential (or diff) which looks at the numbers of the different types of white blood cells. Patients with CLL have too many lymphocytes (calledlymphocytosis). Having more than 10,000 lymphocytes/mm³ (per cubic millimeter) of blood makes the diagnosis almost certain, but it may need to be confirmed by the more specialized tests discussed below. The patient will often have too few red blood cells and blood platelets as well. For the peripheral blood smear, a sample of blood is looked at under the microscope. In patients with CLL, the blood smear often shows many abnormal looking lymphocytes calledsmudge cells.

Other blood tests

Other tests may be done to measure the amount of certain chemicals in the blood, but they are not used to diagnose leukemia. In patients already known to have CLL, these tests help detect liver or kidney problems caused by the spread of leukemia cells or due to the side effects of certain chemotherapy (chemo) drugs. These tests also help determine if treatment is needed to correct low or high blood levels of certain minerals. If treatment with the drug rituximab (Rituxan®) is planned, the doctor may order blood tests to check for previous hepatitis infection.

Blood immunoglobulin (antibody) levels may be tested to see if the patient has enough antibodies to fight infections, especially if they have had many recent infections. Another blood protein called beta-2-macroglobulin may be measured. High levels of this protein indicate a more advanced CLL.

Routine microscopic exams

Any samples taken (blood, bone marrow, lymph node tissue, or CSF) 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 blood diseases and cancer).

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.

An important factor is if the cells look mature (like normal blood cells that can fight infections). Some leukemia cells can lack features of normal blood cells and are not effective in fighting infections. The most immature cells are calledlymphoblasts (or blasts). Chronic lymphocytic leukemia cells usually appear mature.

A key feature of a bone marrow sample is its cellularity. Normal bone marrow contains a certain number of blood-forming cells and fat cells. Marrow with too many blood-forming cells is said to be hypercellular. If too few blood-forming cells are found, the marrow is called hypocellular. Doctors also look to see how much of the normal marrow has been replaced by CLL cells.

The pattern of spread of CLL cells in the bone marrow is also important. A pattern where the cells are in small groups (nodular or interstitial pattern) often indicates a better outlook than if the cells are scattered throughout the marrow (adiffuse pattern).

Cytochemistry

For cytochemistry tests, cells are exposed to chemical stains (dyes) that react with only some types of leukemia cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present.

Flow cytometry

This test is important in diagnosing CLL. It looks for certain substances on the outside surface of cells that help identify what types of cells they are.

A sample of cells is treated with special antibodies that stick only to these substances. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will cause them to give off light, which can be measured and analyzed by a computer.

Some doctors are now using flow cytometry (or immunocytochemistry) to test for substances called ZAP-70 and CD38 on the cells. These substances seem to be linked to the type of B lymphocyte involved in the leukemia. Studies suggest that CLL with fewer cells that have these substances seem to have a better outlook. 

Immunocytochemistry

During this test, as in flow cytometry, cells from the blood or bone marrow samples are treated with special antibodies. But instead of using a laser and computer, the sample is treated so that certain types of cells change color when seen under a microscope.

Gene tests

Cytogenetics: For this test, bone marrow cells (or sometimes cells from the blood or other tissues) are grown in the lab, and the chromosomes are examined under a microscope. Because it takes time for the cells to start dividing, this test usually takes weeks to complete. Normal human cells contain 23 pairs of chromosomes, but some cases of CLL have chromosome changes that can be seen under the microscope.

In some cases of CLL, 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. Deletion of part of chromosome 17 (often written as del[17p]) is linked to a poor outlook. 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.

This information may be helpful to determine a patient's prognosis (outlook), but it needs to be looked at along with other factors, such as the stage of CLL. The loss of part of chromosome 13 is usually linked with a slower growing disease and a better outlook, while defects in chromosomes 11 or 17 often indicate a poorer outlook. Trisomy 12 does not seem to have much of an effect on prognosis.

Fluorescent in situ hybridization (FISH): This is a type of chromosome test that 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 is used to look for certain chromosome changes (not just any change). It can be used on regular blood or bone marrow samples. Because the cells don’t have to grow in the lab first, it can usually provide results more quickly than cytogenetics, often within a couple of days.

Molecular tests: Whether the gene for the immunoglobulin heavy chain variable region (IgVH) has changed (mutated) can help your doctor know how aggressive your CLL is. In order to check for the change, that gene is looked at in a test called DNA sequencing.

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 the leukemia, but they may be done for a number of reasons, including to help find a suspicious area that might be cancerous, to learn how far a cancer may have spread, and to help determine if treatment has been effective.

Computed tomography (CT) scan

The 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).

This test can help tell if any lymph nodes or organs in your body are enlarged. It isn't usually needed to diagnose CLL, but it may be done if your doctor suspects the leukemia is growing in an organ, like your spleen.

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.

Before the scan, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV line through which the contrast dye is injected. The injection of contrast dye can cause a feeling of flushing or warmth in the face or elsewhere. Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lay in when the pictures are being taken.

Sometimes a CT scan is combined with a PET scan in a test known as a PET/CT scan. For a PET scan, glucose (a form of sugar) containing a radioactive atom is injected into the blood. Because cancer cells in the body 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. The PET/CT scan combines both tests in one machine. 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.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into very detailed images of parts of the body. A contrast material called gadolinium may be injected into a vein before the scan to better see details.

MRI scans are most useful in looking the brain and spinal cord, but they are not often needed in people with CLL.

MRI scans take longer than CT scans -- often up to an hour. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you may find disturbing. Some places provide headphones or earplugs to help block this noise out.

Ultrasound

Ultrasound uses sound waves and their echoes to produce 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 over the area to be examined (which is first lubricated with gel). It emits sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image 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.

This is an easy test to have done, and it uses no radiation. For most ultrasound exams, you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.

Chest x-ray

A plain x-ray of your chest can be done in most outpatient settings. In patients with CLL, it isn't needed for a diagnosis, but it may be used to see if you have normal lungs or if you have an infection.

How is chronic lymphocytic leukemia staged?

For most cancers, staging is the process of finding out how far the cancer has spread. Stages are often useful because they can help guide treatment and determine a person's prognosis (outlook). Most types of cancer are staged based on the size of the tumor and how far in the body the cancer has spread.

Chronic lymphocytic leukemia (CLL), on the other hand, does not usually form tumor masses. It generally involves all of the bone marrow in the body and, in many cases, has spread to other organs such as the spleen, liver, and lymph nodes when it is found. Therefore the outlook for the patient with CLL depends on other information, such as the lab test results and the results of imaging tests.

Staging for chronic lymphocytic leukemia

A staging system is a standardized way for the cancer care team to summarize information about how far a cancer has spread. There are 2 different systems for staging CLL:

Rai system: This is used more often in the United States.

Binet system: This is used more widely in Europe.

There are also other factors that have been found to affect prognosis, which are discussed below.

Rai staging system

The Rai system divides CLL into 5 stages:

Rai stage 0: The blood lymphocyte count is too high, usually defined as over 10,000 lymphocytes/mm3 of blood (this is called lymphocytosis). Some doctors will diagnose CLL if the count is over 5,000/mm3 and the cells all have the same chemical pattern on special testing. The lymph nodes, spleen, and liver are not enlarged and the red blood cell and platelet counts are near normal.

Rai stage I: Lymphocytosis plus enlarged lymph nodes. The spleen and liver are not enlarged and the red blood cell and platelet counts are near normal.

Rai stage II: Lymphocytosis plus an enlarged spleen (and possibly an enlarged liver), with or without enlarged lymph nodes. The red blood cell and platelet counts are near normal.

Rai stage III: Lymphocytosis plus anemia (too few red blood cells), with or without enlarged lymph nodes, spleen, or liver. Platelet counts are near normal.

Rai stage IV: Lymphocytosis plus thrombocytopenia (too few blood platelets), with or without anemia, enlarged lymph nodes, spleen, or liver.

For practical purposes, doctors separate the Rai stages into low-, intermediate-, and high-risk groups when determining treatment options.

Stage 0 is considered low risk.

Stages I and II are considered intermediate risk.

Stages III and IV are considered high risk.

Binet staging system

In the Binet staging system, CLL is classified by the number of affected lymphoid tissue groups (neck lymph nodes, groin lymph nodes, underarm lymph nodes, spleen, and liver) and by whether or not the patient has anemia (too few red blood cells) or thrombocytopenia (too few blood platelets).

Binet stage A: Fewer than 3 areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.

Binet stage B: 3 or more areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.

Binet stage C: Anemia and/or thrombocytopenia are present.

Both of these staging systems are helpful and have been in use for many years.

In recent years, doctors have found that other factors can also help predict a person's outlook. The factors described below are not part of formal staging systems (at least at this time), but they can also provide helpful information.

Prognostic factors for chronic lymphocytic leukemia

Along with the stage, there are other factors that help predict a person's outlook. These factors are sometimes taken into account when looking at possible treatment options. Factors that tend to be linked with shorter survival time are called adverse prognostic factors. Those that predict longer survival are favorable prognostic factors.

Adverse prognostic factors

Diffuse pattern of bone marrow involvement (more widespread replacement of normal marrow by leukemia)

Advanced age

Male gender

Deletions of parts of chromosomes 17 or 11

High blood levels of certain substances, such as beta-2-microglobulin

Lymphocyte doubling time (the time it takes for the lymphocyte count to double) of less than 12 months

Increased proportion of large or atypical lymphocytes in the blood

High proportion of CLL cells containing ZAP-70 (more than 20%) or CD38 (more than 30%)

CLL cells with unchanged (not mutated) gene for the immunoglobulin heavy chain variable region (IgVH)

Favorable prognostic factors

Non-diffuse (nodular or interstitial) pattern of bone marrow involvement

Deletion of part of chromosome 13 (with no other chromosome abnormalities)

Low proportion of CLL cells containing ZAP-70 (20% or less) or CD38 (30% or less)

CLL cells with a mutated gene for the immunoglobulin heavy chain variable region (IgVH)

Some of these prognostic factors, such as the presence or absence of ZAP-70 and CD38, will probably become more important over time, and may eventually be found to be better predictors of outcome than the staging systems, particularly for people in the earliest stages of CLL.

Staging for hairy cell leukemia

There is no generally accepted staging system for hairy cell leukemia.

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