It is very important to diagnose childhood leukemia as early as possible and to determine what type of leukemia it is so that treatment can be tailored to provide the best chance of success. The exams and tests below are used to diagnose the disease, to help determine what type of leukemia it is, and to measure how advanced it may be.

Signs and symptoms of childhood leukemia: Many of the signs and symptoms of childhood leukemia are caused by a lack of normal blood cells, a result of the leukemia cells crowding out the normal blood cell-making cells in the bone marrow. As a result, a child may 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. The leukemia cells may also invade other areas of the body, which can also cause symptoms.

Many of these symptoms have other causes as well, and most often they are not due to leukemia. Still, it's important to let your child's doctor know about them so that the cause can be found and treated, if needed.

Fatigue, pale skin: Anemia (a shortage of red blood cells) may cause a child to feel tired, weak, dizzy, or short of breath. It may also cause the skin to appear pale.

Infections and fever: A child with leukemia may develop fever. This is often caused by an infection, which may not improve even with antibiotics. This is because of a lack of normal white blood cells, which would normally help fight the infection. Although children with leukemia may have very high white blood cell counts, the leukemia cells do not protect against infection the way normal white blood cells do. Fever is also sometimes caused by the leukemia cells themselves releasing certain chemicals into the body.

Easy bleeding or bruising: A child with leukemia may bruise easily, have frequent nosebleeds and bleeding gums, or bleed excessively from small cuts. There may be pinhead-sized red spots on the skin caused by bleeding from tiny blood vessels. This comes from a lack of blood platelets, which normally stop bleeding by plugging holes in damaged blood vessels.

Bone or joint pain: Some children with leukemia will have bone pain or joint pain. This is from the buildup of leukemia cells near the surface of the bone or inside the joint.

Swelling of 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 often feel them.

Loss of appetite, weight loss: If the spleen and/or liver become large enough, they may press against other organs like the stomach. This can limit the amount of food that can be eaten, leading to a loss of appetite and weight loss over time.

Swollen lymph nodes: Some leukemias may spread to lymph nodes. The child, a parent, or a health care professional may notice swollen nodes as lumps under the skin in certain areas of the body (such as on the sides of the neck, in underarm areas, above the collarbone, or in the groin). Lymph nodes inside the chest or abdomen may also swell, but these can only be detected by imaging tests, such as CT or MRI scans.

Lymph nodes often enlarge when they are fighting an infection, especially in infants and children. Lymph nodes that grow as a reaction to infection are called reactive nodes or hyperplastic nodes. An enlarged lymph node in a child is more often a sign of infection than leukemia, but it should be checked by a doctor and followed closely.

Coughing or trouble breathing: The T-cell type of acute lymphocytic leukemia (ALL) often involves the thymus, which is a small organ in the chest behind the breastbone (sternum) and in front of the windpipe (trachea). Enlargement of the thymus or of lymph nodes inside the chest can press on the trachea. This can lead to coughing or trouble breathing.

Swelling of the face and arms: 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 skin 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.

Headache, seizures, vomiting: Leukemia can spread outside the bone marrow. It may spread to the central nervous system (brain and spinal cord), the testicles, ovaries, kidneys, lungs, heart, intestines, or other organs. A small portion of children have leukemia that has already spread to the central nervous system when they are first diagnosed. Headache, trouble concentrating, weakness, seizures, vomiting, problems with balance, and blurred vision can be symptoms of central nervous system leukemia.

Rashes, gum problems: In children with acute myelogenous leukemia (AML), leukemia cells may spread to the gums, causing swelling, pain, and bleeding. Spread to the skin can cause small, darkly colored spots that can resemble common rashes. A collection of AML cells under the skin or in other parts of the body is called a chloromaor granulocytic sarcoma.

Extreme fatigue, weakness: One rare but very serious consequence of AML is extreme tiredness, weakness, and slurring of speech. This can occur when very high numbers of leukemia cells make the blood too "thick" and slow the circulation through small blood vessels of the brain.

Medical history and physical exam:If your child has signs and symptoms that suggest they may have leukemia, the doctor will want to get a thorough medical history, including how long the symptoms have been present and whether or not there is any history of exposure to risk factors. A family history of cancer, especially leukemia, may also be important.

During the physical exam, the doctor will focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes, mouth, and skin will likely be looked at carefully, and a nervous system exam may be done. The abdomen will be felt for signs of an enlarged spleen or liver.

The doctor may also get blood samples to test your child's blood cell counts. If these are abnormal, the doctor may refer you to a pediatric oncologist, a doctor who specializes in treating cancers (like leukemia) in children. This doctor may run one or more of the tests described below.

Types of tests used to look for leukemia in children: If the doctor thinks your child might have leukemia, he or she will need to check samples of cells from your child's blood and bone marrow to be sure of the diagnosis. Other tissue and cell samples may also be taken to help guide treatment.

Blood tests:Blood samples for tests for leukemia are taken as they are for other tests – usually from a vein in the arm. In infants and younger children, they may be taken from other veins (such as in the feet or scalp) or from a "finger stick."

Blood counts and blood smears are the usual tests done on these samples. A complete blood count (CBC) is done to determine how many of each type of blood cell are present in the blood. For a blood smear, a small sample of blood is spread on a glass slide and looked at under a microscope. Abnormal numbers of different blood cell types and changes in the way these cells look may make the doctor suspect leukemia.

Most children with acute leukemia — lymphocytic or myeloid — will have too many white blood cells and not enough red blood cells and/or platelets. Many of the white blood cells in the blood will be blasts, an early type of blood cell normally found only in the bone marrow. Even though these findings may make a doctor suspect that a child has leukemia, usually the disease cannot be diagnosed for sure without looking at a sample of bone marrow cells.

Bone marrow aspiration and biopsy:Bone marrow samples are obtained from a bone marrow aspiration and biopsy – 2 tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bones, but in some cases they may be taken from the front of the pelvic bones, the breastbone (sternum [very rarely in children]), or other bones.

For a bone marrow aspiration, the skin over the hip and the surface of the bone is cleaned and numbed with local anesthetic. In most cases, the child is also given other medicines to reduce pain or even be asleep during the procedure. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out (aspirate) a small amount of liquid bone marrow.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is twisted as it is pushed down into the bone. Once the biopsy is done, pressure will be applied to the site to help prevent any bleeding.

These bone marrow tests are used to diagnose leukemia and may be repeated later to tell if the leukemia is responding to treatment.

Lumbar puncture (spinal tap):This test is used to look for leukemia cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord.

For this test, the doctor first numbs an area in the lower part of the back over the spine. The doctor usually also gives the child medicine to make him or her sleep during the procedure. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.

This test is routinely done in children with leukemia, but it is important that it is done by an expert. Doctors have found that if the spinal tap isn't performed expertly and some blood leaks into the CSF, in some cases leukemia cells may escape into the fluid and grow there.

In children already diagnosed with leukemia, a lumbar puncture can also be used to give chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.

Lymph node biopsy:This type of biopsy is important in diagnosing lymphomas, but it is rarely needed for children with leukemias.

During this procedure, a surgeon cuts through the skin to remove an entire lymph node (excisional biopsy). If the node is near the skin surface, this is a simple operation. But it may be more involved if the node is inside the chest or abdomen. Most often the child will need general anesthesia (where the child is asleep).

Lab tests used to diagnose and classify leukemia

Routine microscopic exams:As mentioned above, blood counts and smears are usually the first tests done when leukemia is a possible diagnosis. Any other samples taken (bone marrow, lymph node tissue, or CSF) are also 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 staining patterns of the blood cells in the samples to classify them into specific types.

A key element is whether the cells look mature (like normal blood cells) or immature (lacking features of normal blood cells). The most immature cells are called blasts. Having too many blasts in the sample, especially in the blood, is a typical sign of leukemia.

An important 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.

Cytochemistry:In cytochemistry tests, cells from the sample are put on a microscope slide and 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. This can help the doctor determine what types of cells are present. For example, one 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 used to test the cells from bone marrow, lymph nodes, and blood samples to determine more accurately the exact type of leukemia. It is a very important tool because it may help define the unique traits of the leukemia. It can also be used to measure the response to treatment and the existence of minimal residual disease  in some types of leukemias.

The test checks for certain substances on the surface of cells that help identify what types of cells they are. The cells in the sample are treated with special antibodies (man-made versions of immune system proteins) 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 is measured and analyzed by a computer.

Flow cytometry can also be used to estimate the amount of DNA in the leukemia cells. This is important to know, especially in ALL, because cells with a high DNA index (more than 16% above normal) are often more sensitive to chemotherapy, and these leukemias have a better prognosis (outlook).

For immunohistochemistry tests, cells from the bone marrow or other samples are treated with special man-made antibodies. But instead of using a laser and computer for analysis, the sample is treated so that certain types of cells change color. The color change is visible under a microscope. Like flow cytometry, it is helpful in distinguishing different types of leukemia from one another and from other diseases.

These tests are used for immunophenotyping – classifying leukemia cells according to the substances (antigens) on their surfaces. Different types of cells have different antigens on their surface. These antigens also change as the cells mature. 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 and classify leukemias.

Cytogenetics:For this test, chromosomes (pieces of DNA) from leukemia cells 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 types of leukemia, chromosome changes may be seen.

For instance, sometimes 2 chromosomes 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 acute leukemias and can help determine prognosis (outlook).

Some types of leukemia have cells with an abnormal number of chromosomes (instead of the usual 46) – they may be missing some chromosomes or have extra copies of some. This can also affect a patient's outlook. For example, chemotherapy is more likely to work in cases of ALL where the cells have more than 50 chromosomes and is less likely to be effective if the cells have fewer than 46 chromosomes. (Counting the number of chromosomes by cytogenetics provides similar information to measuring the DNA index by flow cytometry, as described above.)

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 looked at under the microscope.

Not all chromosome changes can be seen under a microscope. Other lab tests can often help detect 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 blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days.

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. Like flow cytometry, it can be a very useful tool to look for small numbers of leukemia cells (minimal residual disease, or MRD) during and after treatment.

These tests may also be used after treatment to see if even small numbers of leukemia cells, which would not be detected by other tests, are still there.

Other blood tests:Children with leukemia will have tests to measure certain chemicals in the blood to evaluate how well their body systems are working.

These tests are not used to diagnose leukemia, but in children already known to have it, they can help find damage to the liver, kidneys, or other organs caused by the spread of leukemia cells or by certain chemotherapy drugs. Tests are also often done to measure blood levels of important minerals, as well as to ensure the blood is clotting properly.

Children might also be tested for blood infections. It is important to quickly diagnose and treat infections in children with leukemia because their weakened immune systems can allow infections to spread quickly.

Imaging tests:Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. Leukemia does not usually form tumors, so imaging tests aren't as useful as they are for other types of cancer. But if leukemia is suspected or has been diagnosed, your child's doctor may order some of the following imaging tests to get a better idea of the extent of the disease or to look for other problems, such as infections.

Chest x-rays:A chest x-ray can help detect an enlarged thymus or lymph nodes in the chest. If this test is abnormal, a computed tomography (CT) scan may be done to get a more detailed view. Chest x-rays can also help look for pneumonia if your child seems to have a lung infection.

Computed tomography (CT) scan:The CT scan is a type of x-ray test that produces detailed, cross-sectional images of the 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 the body are enlarged. It isn't usually needed to diagnose leukemia, but it may be done if the doctor suspects the leukemia is growing in lymph nodes in the chest or in organs like the spleen or liver. It is also sometimes used to look at the brain and spinal cord, but MRI may also be used for this.

Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around your child. A computer then combines these pictures into detailed images of the part of the body that is being studied.

Before the scan, your child 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. He or she 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 your child has any allergies or has ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. Your child will need to lie still on a table while the scan is being done. During the test, the table slides in and out of the scanner, a ring-shaped machine that completely surrounds the table. Some children may need to be sedated before the test. Spiral CT (also known as helical CT) is now used in many medical centers. This type of CT scan uses a faster machine with a lower dose of radiation, but gives more detailed pictures.

PET/CT scan: In recent years, newer devices have been developed that combine the CT scan with a positron emission tomography (PET) scan. For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) 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 lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.

Magnetic resonance imaging (MRI) scans:Like CT scans, MRI scans give 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 show details. The contrast material usually does not cause allergic reactions.

MRI scans are most helpful in looking at the brain and spinal cord.

MRI scans take longer than CT scans – often up to an hour. Your child may have to lie inside a narrow tube, which is confining and can be distressing, so sedation is sometimes needed. Newer, more open MRI machines may be another option, although they still require that your child be able to lie still. All MRI machines make loud buzzing and clicking noises that your child 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). 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 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 the abdomen such as the kidneys, liver, and spleen. (It can't be used to look at organs or lymph nodes in the chest because the ribs block the sound waves.)

This is an easy test to have, and it uses no radiation. Your child simply lies on a table, and a technician moves the transducer over the part of the body being looked at.

Gallium scan and bone scan:These tests are not often done for childhood leukemias, but they may be useful if your child has bone pain that might be from either an infection or cancer in the bones. If your child has already been diagnosed with leukemia or if a PET scan (described above) has already been done, there is usually no need for these tests.

For these tests, the doctor or nurse injects a small amount of a slightly radioactive chemical into the bloodstream, which collects in areas of cancer or infection in the body. These areas can then be looked at 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 or CT or MRI scans 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.