Signs and Symptoms of Childhood Leukemia

Many of the signs and symptoms of childhood leukemia result from a lack of normal blood cells, which happens when the leukemia cells crowd out the normal blood cell-making cells in the bone marrow. The leukemia cells may also invade other areas of the body, which can also cause symptoms. It is important to keep in mind that many of these symptoms have other causes as well, and are most often not due to leukemia.

Fatigue, Paleness of the Skin

A child may complain of excessive tiredness, or the skin may appear pale because of anemia (a shortage of red blood cells).

Infections and Fever

A child with leukemia may develop fever. This is often due to infections, which may not improve even with antibiotics. This is because of a lack of normal white blood cells, particularly mature granulocytes, 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 sometimes caused by the leukemia cells themselves releasing certain chemicals into the body.

Easy Bleeding or Bruising

A child with leukemia may bruise easily or have increased bleeding from small cuts and nosebleeds. There may be pinhead-sized red spots on the skin that represent 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 Pain

About 1 out of 3 children with leukemia will have bone pain. A smaller number will have joint pain. This is due to 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 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 (on the sides of the neck, in the groin, underarm areas, above the collarbone, etc.). Swelling of lymph nodes inside the chest or abdomen may also occur, 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 gland, which is located in the front of the chest. Enlargement of the thymus or of lymph nodes inside the chest can press on the nearby trachea (windpipe). This can lead to coughing, shortness of breath, or even suffocation.

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 and arms and a bluish-red coloration of the head, arms, and upper chest. It can also cause trouble breathing and a change in consciousness if it affects the brain. The SVC syndrome can be life-threatening, and requires immediate attention.

Headache, Seizures, Vomiting

Leukemia can spread outside the bone marrow. It may involve the central nervous system (brain and spinal cord), the testicles, ovaries, kidneys, lungs, heart, intestines, or other organs. About 5% to 10% 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 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 other parts of the body is called a chloroma or granulocytic sarcoma.

Extreme Fatigue, Weakness

One rare but very serious consequence of AML is extreme tiredness, weakness, and slurring of speech, which occurs when very high numbers of leukemia cells make the blood too "thick" and interfere with circulation through small blood vessels of the brain.

Most of the symptoms seen in leukemia can also be seen in other problems like infections. For this reason, an accurate diagnosis is crucial.

Medical History and Physical Exam

If any of the signs and symptoms above suggest the possibility of leukemia, the doctor will want to get a thorough medical history, including how long any 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.

The physical exam will likely focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes and mouth will likely be looked at carefully. The abdomen will be felt thoroughly for signs of an enlarged spleen or liver.

If there is any reason to think there might be problems caused by abnormal numbers of blood cells (anemia, infections, bleeding or bruising, etc.), the doctor will likely test your child's blood counts. If these are abnormal, the doctor may refer you to a childhood cancer doctor, who may run one or more of the tests described below.

Types of Samples Used to Test for Leukemia in Children

Blood Samples

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 is present in the blood. A blood smear involves spreading a small sample of blood on a glass slide and looking at the blood cells under a microscope. Changes in the numbers of different cell types in the blood and the way these cells look under the microscope may make the doctor suspect leukemia.

Most children with acute leukemia (ALL or AML) will have too many white blood cells and not enough red blood cells and/or not enough platelets. Many of the white blood cells in the blood will be blasts, a type of cell normally found only in the bone marrow. Even though these findings may make a doctor suspect that leukemia is present, usually the disease cannot be diagnosed for sure without getting a sample of bone marrow cells.

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, the skin over the hip and the surface of the bone are numbed with local anesthetic. In some 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 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 (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. Once the biopsy is done, pressure will be applied to the site to help prevent any bleeding

These tests are used for the initial diagnosis and may be repeated later to tell if the leukemia is responding to therapy.

Lumbar Puncture (Spinal Tap)

This procedure is used to look for leukemia cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord. A lumbar puncture can also be used to give chemotherapy drugs into the CSF to prevent or treat spread of leukemia to the spinal cord and brain.

For this test, the doctor first numbs an area in the lower part of the back near the spine. The doctor may also recommend that the child be given something to make him or her sleep so the child won't squirm during the procedure. Squirming may keep the spinal tap from being done cleanly. A small needle is then placed between the bones of the spine to withdraw some of the fluid.

Although this procedure is routinely done in children with leukemia, it is important that it is done by someone who is an expert. Doctors have found that if the spinal tap isn't performed expertly and some blood leaks into the spinal fluid, leukemia cells may escape into the spinal fluid and grow there.

Lymph Node Biopsy

During this procedure, a surgeon cuts through the skin to remove the entire lymph node (excisional biopsy). If the node is near the skin surface, this is a simple operation that can be done with local anesthesia (numbing medicine used only at the biopsy site). But if the node is inside the chest or abdomen, then the child will need general anesthesia (where the child is asleep). This procedure is important in diagnosing lymphomas, but is rarely needed for children with leukemias.

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 diagnosing diseases with lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in treating 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. (See the section, "How Is Childhood Leukemia Classified?" for more information on the types of leukemia.)

An important factor is if the cells look mature (like normal circulating blood cells that can fight infections). Some leukemic cells can lack features of normal blood cells and are not effective in fighting infections. The most immature cells are called "blasts".

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

During this test, cells from the sample 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 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

This technique is sometimes used to test the cells from bone marrow, lymph nodes, and blood samples. It is very accurate in determining the exact type of leukemia.

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 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).

Immunocytochemistry

As in flow cytometry, this technique involves treating cells from the bone marrow or other samples with special manmade 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.

Cytogenetics

This test involves looking at chromosomes (pieces of DNA) under a high-powered 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 certain types of leukemia, chromosome changes may be seen.

For instance, sometimes two chromosomes swap some of their genetic material, leaving one longer than normal and one shorter than normal. This change, called a translocation, can usually be seen under a microscope. Recognizing these translocations can help identify certain types of ALL and AML 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 copies of some chromosomes or have extra copies of some. This can also affect a patient's outlook. For example, most cases of ALL where the cells have more than 50 chromosomes are more sensitive to chemotherapy, while those where the cells have fewer than 46 are more resistant to it. (Counting the number of chromosomes by cytogenetics provides similar information to measuring the DNA index by flow cytometry, as described above.)

Fluorescent in situ hybridization (FISH) is a type of cytogenetic test. It uses special fluorescent dyes that only attach to specific parts of chromosomes. FISH can be used to look for specific changes in chromosomes. It can be used on regular blood or bone marrow samples and is very accurate, which is why this test is now used in many medical centers.

Molecular Genetic Studies

Certain substances, called antigens, are on the surface of lymphocytes. These antigens are proteins that normally help immune system cells recognize other types of cells and each other. Different types of lymphocytes have different antigens on their surface. These antigens may also change as each cell matures.

Lymphocytic leukemias such as ALL start from a single abnormal lymphocyte, so all the cells in each patient's leukemia have the same antigens. These antigens can be tested for using special man-made antibodies that react only to a specific antigen. Lab tests for antigens are a very sensitive way to diagnose ALL. Because different subtypes of ALL cells have different sets of antigens, this test is sometimes helpful in ALL classification, although it is not needed in most cases.

Tests of leukemia cell DNA can detect most translocations that are visible under a microscope in cytogenetic tests. Sensitive DNA tests such as polymerase chain reaction (PCR) can also find translocations too small to be seen under a microscope. This testing is sometimes helpful in leukemia classification because many subtypes of ALL and AML have distinctive translocations. This information may be useful in predicting response to treatment. See "What's New in Childhood Leukemia Research and Treatment?" for information on recent advances in genetics.

Other Blood Tests

Children with leukemia will have tests to measure the amount of 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 help find liver or kidney problems from damage caused by the spread of leukemic cells or the side effects of certain chemotherapy drugs. Tests are often done to measure blood levels of important minerals, as well as to ensure the blood is clotting properly, as well.

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

Imaging Tests

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.

Chest X-rays

A chest x-ray can help detect enlargement of the thymus or lymph nodes in the chest. If this test is abnormal, a computed tomography (CT) scan may be done to get more detail on the extent of the disease.

Chest x-rays can also help find pneumonia if your child appears to have an 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, although MRI may also be sued 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 your body that is being studied.

Often after the first set of pictures is taken, your child will receive an intravenous (IV) injection of a contrast dye or your child may be asked to drink a solution of contrast material. This helps better outline blood vessels and internal organs. A second set of pictures is then taken.

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 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 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.

Magnetic Resonance Imaging (MRI) Scans

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. Not only does this create images of cross-sectional slices of the body like a CT scanner, it can also produce images of slices that are parallel with the length of the body. A contrast material might be injected, just as with CT scans, but is used less often.

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, "open" MRI machines may be another option. The MRI machine makes loud buzzing noises that your child may find disturbing. Some places provide headphones to block this out.

Ultrasound (Ultrasonography)

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 oil). 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 that is displayed on a computer screen.

Ultrasound can be used to look for enlarged organs inside the abdomen.

This is an easy test to have done, 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 may be useful if your child has bone pain that might be due to either bone infection or cancer involving bones. If your child has already been diagnosed with leukemia, there is usually no need for these studies.

For these tests, the radiologist injects a small amount of a 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, x-rays of the affected area can be done to get a more detailed look. If leukemia is a possibility, a biopsy of the area may be needed to confirm this.

Last Medical Review: 08/19/2007
Last Revised: 05/14/2009