Certain signs and symptoms might suggest that a person may have acute lymphocytic leukemia (ALL), but tests are needed to confirm the diagnosis.
Signs and symptoms of acute lymphocytic leukemia
Acute lymphocytic leukemia (ALL) can cause many different signs and symptoms. Most of these occur in all kinds of ALL, but some are more common with certain subtypes.
Generalized symptoms
Patients with ALL often have several non-specific symptoms. These can include weight loss, fever, night sweats, fatigue, and loss of appetite. Of course, these are not just symptoms of ALL and are more often caused by something other than leukemia.
Shortage of blood cells
Most signs and symptoms of ALL result from a shortage of normal blood cells, which happens when the leukemia cells crowd out the normal blood-making cells in the bone marrow. As a result, people do not have enough normal red blood cells, white blood cells, and blood platelets. These shortages show up on blood tests, but they can also cause symptoms.
- Anemia is a shortage of red blood cells. It can cause a person to feel tired, weak, dizzy, cold, lightheaded, or short 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 ALL may have high white blood cell counts due to excess numbers of leukemia cells, but these cells do not protect against infection the way normal white blood cells do. Fevers and recurring infections are some of the most common symptoms of ALL.
- A shortage of blood platelets (thrombocytopenia) can lead to excess bruising, bleeding, frequent or severe nosebleeds, and bleeding gums.
Swelling in the abdomen
Leukemia cells may collect in the liver and spleen, causing them to enlarge. This may be noticed as a fullness or swelling of the belly. The lower ribs usually cover these organs, but when they are enlarged the doctor can feel them.
Enlarged lymph nodes
Acute lymphocytic leukemia may spread to lymph nodes. If the affected nodes are close to the surface of the body (on the sides of the neck, in the groin, in underarm areas, above the collarbone, etc.), they may be noticed as lumps under the skin. Lymph nodes inside the chest or abdomen may also swell, but these can be detected only by imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) scans.
Spread to other organs
Less often, ALL may spread to other organs. If it spreads to the brain and spinal cord (central nervous system, or CNS) it can cause headaches, weakness, seizures, vomiting, trouble with balance, facial numbness, or blurred vision. ALL may also spread to the chest cavity, where it can cause fluid buildup and trouble breathing. On rare occasions it may spread to the skin, eyes, testicles, kidneys, or other organs.
Bone or joint pain
Some patients have bone pain or joint pain caused by the buildup of leukemia cells near the surface of the bone or inside the joint.
Enlarged thymus gland
The T-cell subtype of ALL often affects the thymus, which is a small gland in the middle of the chest located behind the sternum (breastbone) and in front of the trachea (windpipe). An enlarged thymus can press on the trachea, causing coughing or trouble breathing.
The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. Growth of the thymus due to excess leukemia cells may press on the SVC, causing the blood to "back up" in the veins. This is known as SVC syndrome. It can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. The SVC syndrome can be life-threatening, and needs to be treated right away.
Medical history and physical exam
If any signs and symptoms suggest the possibility of leukemia, the doctor will want to get a thorough medical history, including how long symptoms have been present and whether or not there is any history of exposure to risk factors.
During the physical exam, the doctor will probably focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes, mouth, and skin will be looked at carefully, and a thorough nervous system exam will be done. The abdomen will be felt for signs of an enlarged spleen or liver.
If there is reason to think the problems might be caused by abnormal numbers of blood cells (anemia, infections, bleeding or bruising, etc.), the doctor will likely test your blood counts. If the results suggest leukemia may be the cause, the doctor may refer you to a cancer doctor, who may run one or more of the tests described below.
Types of samples used to test for acute lymphocytic leukemia
If signs and symptoms and/or the results of the physical exam suggest you may have leukemia, the doctor will need to check samples of cells from your blood and bone marrow to be sure of the diagnosis. Other tissue and cell samples may also be taken to help guide treatment.
Blood samples
Blood samples for tests for ALL are generally taken from a vein in the arm.
Bone marrow samples
Bone marrow samples are obtained from a bone marrow aspiration and biopsy -- two tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases 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 skin 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 briefly cause some pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.
These bone marrow tests are used to help diagnose leukemia. They may also be done again later to tell if the leukemia is responding to treatment.
Lumbar puncture (spinal tap)
This important test looks for leukemia cells in the cerebrospinal fluid (CSF), which is the liquid that surrounds the brain and spinal cord. A lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.
For this test, the patient may be lying on their side or sitting up. 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.
Excisional lymph node biopsy
This is often an important procedure when diagnosing lymphomas, but is only rarely needed with leukemias.
In this procedure, a surgeon cuts through the skin to remove an entire lymph node. If the node is near the skin surface, this is a simple operation that can often be done with local anesthesia, but if the node is inside the chest or abdomen, general anesthesia (where the patient is asleep) is used.
Lab tests used to diagnose and classify acute lymphocytic leukemia
One or more of the following lab tests may be done on the samples to diagnose ALL, to determine what subtype of ALL it is, and/or to help determine how advanced the disease is.
Blood cell counts and blood cell exam (peripheral blood smear)
These tests look at the numbers of the different types of blood cells and at how they look under the microscope. Changes in the numbers and the appearance of these cells often help diagnose leukemia.
Most patients with ALL have too many immature white cells in their blood, and not enough red blood cells or platelets. Many of the white blood cells will be lymphoblasts (blasts), which are immature lymphocytes not normally found in the bloodstream. These immature cells do not function like normal, mature white blood cells. Even though these findings may suggest leukemia, the disease usually is not diagnosed without looking at a sample of bone marrow cells.
Blood chemistry and coagulation tests
Blood chemistry tests measure the amounts of certain chemicals in the blood, but they are not used to diagnose leukemia. In patients already known to have ALL, these tests can help detect liver or kidney problems caused by spreading leukemia cells or 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.
Blood coagulation tests may also be done to make sure the blood is clotting properly.
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 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 element is whether the cells appear mature (look like normal blood cells), or immature (lacking features of normal blood cells). The most immature cells are called lymphoblasts (or "blasts" for short).
Determining what percentage of cells in the bone marrow are blasts is particularly important. A diagnosis of ALL generally requires that at least 20% to 30% of the cells in the bone marrow are blasts. Under normal circumstances, blasts are never more than 5% of bone marrow cells.
Sometimes just counting and looking at the cells does not provide a definite diagnosis, and other lab tests are needed.
Cytochemistry
In cytochemistry tests, cells are exposed to chemical stains (dyes) that react only with 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. For instance, one stain can help distinguish ALL from acute myeloid leukemia (AML). The stain causes the granules of most AML cells to appear as black spots under the microscope, but it does not cause ALL cells to change colors.
Flow cytometry and immunohistochemistry
Flow cytometry is often used to look at the cells from bone marrow, lymph nodes, and blood samples. It is very helpful in determining the exact type of leukemia.
The test looks for certain substances on the surface of cells that help identify what types of cells they are. A sample of cells is treated with special antibodies (man-made versions of immune system proteins) that stick to the cells only if these substances are present on their surfaces. 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. Groups of cells can be separated and counted by these methods.
In immunohistochemistry tests, cells from the blood or bone marrow samples are also 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.
These tests are used for immunophenotyping -- classifying leukemia cells according to the substances (antigens) on their surfaces. Different types of lymphocytes have different antigens on their surface. These antigens also change as each cell matures. Each patient's leukemia cells should all have the same antigens because they are all derived from the same cell. Lab testing for antigens is a very sensitive way to diagnose ALL. Because cells from different subtypes of ALL have different sets of antigens, this is sometimes helpful in ALL classification, although it is not needed in most cases.
Cytogenetics
For this test, chromosomes (long strands of DNA) are looked at under a microscope to detect any changes. Normal human cells contain 23 pairs of chromosomes, each of which is a certain size and stains a certain way. In some cases of leukemia, the cells have chromosome changes that can be seen under a microscope.
For instance, 2 chromosomes may swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. This change, called a translocation, can usually be seen under a microscope. Recognizing these changes can help identify certain types of ALL and may be important in determining the outlook for the patient.
Most of the chromosome changes in adult ALL are translocations. The most common one is a translocation between chromosomes 9 and 22, which results in a shortened chromosome 22 (called the Philadelphia chromosome). About 25% to 30% of adults with ALL have this abnormality in their leukemia cells.
Information about this and other translocations may be useful in predicting response to treatment. For this reason, most doctors will test all patients with ALL for genetic changes in the leukemia cells.
Cytogenetic testing usually takes about 2 to 3 weeks because the leukemia cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be viewed under the microscope.
Not all chromosome changes can be seen under a microscope. Other lab tests can often help find these changes.
Fluorescent in situ hybridization (FISH)
This is similar to cytogenetic testing. It uses special fluorescent dyes that only attach to specific parts of particular chromosomes. FISH can find most chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.
FISH can be used to look for specific changes in chromosomes. It can be used on regular blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.
Polymerase chain reaction (PCR)
This is a very sensitive DNA test that can also find some chromosome changes too small to be seen under a microscope, even if very few leukemia cells are present in a sample.
These tests may also be used after treatment to try to find small numbers of leukemia cells that may not be visible under a microscope.
Imaging tests
Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. Because leukemia does not usually form visible tumors, imaging tests are of limited value. Imaging tests might be done in people with ALL, but they are done more often to look for infections or other problems, rather than for the leukemia itself. In some cases they may be done to help determine the extent of the disease, if it is thought it may have spread beyond the bone marrow and blood.
X-rays
Routine chest x-rays may be done if the doctor suspects a lung infection. They may also be done to look for enlarged lymph nodes in the chest.
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 ALL, but it may be done if your doctor suspects leukemia cells are growing in an organ, like your spleen.
Instead of taking one picture, as does 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 IV 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.
Spiral CT (also known as helical CT) is now available in many medical centers. This type of CT scan uses a faster machine. The scanner part of the machine rotates around the body continuously, allowing doctors to collect the images much more quickly than standard CT. This lowers the chance of blurred images occurring as a result of body movement. It also lowers the dose of radiation received during the test. The slices it images are thinner, which yields more detailed pictures.
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 stay 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 biopsy sample is then removed to be looked at under a microscope.
Recently, newer devices have been developed that combine the 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 in the body grow rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. The PET/CT scan 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 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. A contrast material called gadolinium is often injected into a vein before the scan to better see details. The contrast material usually does not cause allergic reactions.
MRI scans are very helpful in looking at the brain and spinal cord.
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 out.
Ultrasound
Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. For this test, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with gel). The transducer emits 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 displayed 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 done, and it uses no radiation. You simply lie on a table, and a technician moves the transducer over the part of your body being looked at.
Gallium scan and bone scan
These tests are not often done for ALL, but they may be useful if a patient has bone pain that might be due to either an infection or cancer in the bones.
For these tests, the doctor or nurse injects a slightly radioactive chemical into the bloodstream, which collects in areas of cancer or infection in the body. These areas can then be viewed with a special type of camera. The images from these scans are seen as "hot spots" in the body, but they don't provide much detail. If an area lights up on the scan, other imaging tests such as x-rays, CTs, or MRIs may be done to get a more detailed look at the area. If leukemia is a possibility, a biopsy of the area may be needed to confirm this.