Signs and Symptoms of Childhood Leukemia

Most of the signs and symptoms that children with leukemia develop result from a lack of normal blood cells caused by crowding out of normal blood cell-producing bone marrow by the leukemia cells. A child may complain of shortness of breath, excessive tiredness, or the skin may appear pale because of anemia (a shortage of red blood cells).

Infection: A child with leukemia may develop an infection that doesn't respond to antibiotics, have a high fever, and become very sick. This is because of a deficiency of normal white blood cells, particularly mature granuloctyes. Although leukemia is a cancer of white blood cells and children with leukemia may have very high white blood cell counts, the leukemic cells do not protect against infection the way normal white blood cells do.

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 results from poor production of blood platelets, which are important for plugging holes in damaged blood vessels.

Bone pain: About ? of the children will have bone pain. A smaller number will have joint pain. This is due to accumulation of the leukemia cells underneath the covering of the surface of the bone or inside the joint. Some children will also have a lack of appetite.

Swelling of the abdomen: Leukemia often causes enlargement of the liver and spleen. Enlargement of these organs would be noticed as a fullness, or even swelling, of the belly. The lower ribs usually cover these organs but when they are enlarged, the doctor can feel them.

Swollen lymph nodes: Leukemia can also spread to lymph nodes. The child, a parent, or a health care professional may notice swollen nodes that are close to the surface of the body (lymph nodes 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. These are sometimes detected only by imaging tests, such as CT or MRI scans.

Enlargement of the thymus: The T-cell type of ALL often involves the thymus. Enlargement of the thymus or of lymph nodes inside the chest can compress the nearby trachea (windpipe). This can lead to coughing, shortness of breath, or even suffocation. 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 leukemia cells may compress the SVC causing swelling and bluish-red discoloration of the head, arms, and upper chest. This is known as SVC syndrome, and can affect the brain and threaten the child's life. Patients with SVC syndrome need immediate treatment.

Headache, seizures, vomiting: Leukemia cells can spread outside the bone marrow. This is called "extramedullary spread." It may involve the central nervous system (brain and spinal cord), the testicles, ovaries, kidneys, lungs, heart, intestines, or other organs. Spread to the central nervous system (CNS) at the time of initial diagnosis is seen in 10% to 12% of patients with AML, and about twice as often as in ALL. Headache, poor school performance, weakness, seizures, vomiting, difficulty in maintaining balance, and blurred vision can be symptoms of CNS leukemia.

Rashes, fatigue, weakness: AML can cause some unique symptoms. 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. One unusual but very serious consequence of AML is extreme tiredness, weakness, and slurring of speech, which occurs when very high numbers of leukemic cells make the blood too "thick" and interfere with circulation through small blood vessels of the brain.

Types of Specimens Used to Diagnose Children with Leukemia

Most of the symptoms of leukemia are not unique. Some of these symptoms can also be caused by other problems like infections. For these reasons, an accurate diagnosis is needed and the best way to do this is for your doctor to take cells samples from the child's blood and bone marrow.

Blood cell counts and blood cell examination: Changes in the numbers of different cell types in the blood and the appearance of these cells under the microscope often make the doctor suspect leukemia. Most children with acute leukemia (ALL or AML) will have either too many white cells in their blood and not enough red blood cells (oxygen-carrying cells) and/or not enough platelets (cells that help plug up small holes in blood vessels and stop bleeding from cuts and bruises). In addition, many of the white blood cells in these children's blood will be blasts, a type of cell normally found in the bone marrow but not in circulating blood. Even though these findings may make your doctor suspect that leukemia is present, usually the disease cannot be diagnosed for sure without obtaining a sample of bone marrow cells.

Bone marrow aspiration and biopsy: Bone marrow aspiration involves removing a small amount of bone marrow. Usually the sample is taken from the back of the pelvic bone. The bone is numbed with xylocaine, a local anesthetic. In some cases, the child is also given medications to reduce pain or even put her or him to sleep during the procedure. The needle is then put through the outer bone into the marrow space, and some marrow is removed. A biopsy follows, during which a small cylindrical piece of bone and bone marrow (about 1/16-inch in diameter and 1/2-inch long) is removed. Both samples generally are taken at the same time. These tests are used for the initial diagnosis and are repeated later to tell if the leukemia is responding to therapy.

Other blood tests: Children with leukemia will have tests done to measure the amount of certain chemicals in the blood, in order to evaluate how well their liver and kidneys are working. These tests are not used to diagnose leukemia. But, in children already known to have leukemia, these tests help detect liver or kidney problems due to damage caused by the spread of leukemic cells or the side effects of certain chemotherapy drugs. Tests may also be done to check for spread of infections to the child's bloodstream. Prompt and accurate diagnosis and treatment of infections is important for children with leukemia, because their weakened immune system allows infections to spread quickly.

Lymph node biopsy: 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 medication) in the older, cooperative child. But if the node is inside the chest or abdomen, general anesthesia is used (the child is asleep). This procedure is important in diagnosing lymphomas, but is rarely needed for children with leukemias.

Lumbar puncture (spinal tap): A small needle is inserted into the spinal cavity in the lower back to withdraw some cerebrospinal fluid (CSF) look for leukemia cells. A lumbar puncture is also used to administer chemotherapy drugs into the spinal fluid to prevent or treat spread of leukemia to the spinal cord and brain.

Laboratory Tests Used to Diagnose and Classify Leukemia

Using a microscope, a doctor will examine all bone marrow aspirates and biopsy specimens, all lymph node biopsy specimens, all CSF specimens, and any blood smears with significant abnormalities. This doctor has special training in recognizing cells from blood and lymphoid tissue diseases. The doctor may be a pathologist (doctor specializing in diagnosis of disease by laboratory tests) or a hematologist/oncologist (doctor specializing in medical treatment of cancer and blood diseases). The doctors will look at the size and shape of the cells and other aspects of their appearance.

Cytochemistry: After cells from a sample are placed on glass microscope slides, they are stained with dyes that are attracted to certain chemicals only present in some types of leukemia cells. 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 examine the cells from bone marrow, lymph nodes, and blood samples. It is very accurate in determining the exact type of leukemia. The cells being examined by flow cytometry are treated with selected antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of leukemia cells. If the sample contains those cells, the laser will cause them to give off light, which is measured and analyzed by a computer. Flow cytometry is also used to estimate the amount of DNA in the leukemia cells. ALL cells with high DNA content, more than 16% above normal, are more sensitive to chemotherapy.

Immunocytochemistry: As in flow cytometry, cells from the bone marrow aspiration or biopsy sample are treated with special laboratory 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 detectable under a microscope. Like flow cytometry, it is helpful in distinguishing different types of leukemia from one another and from other diseases.

Cytogenetics: Normal human cells contain 46 chromosomes (pieces of DNA and protein that control cell growth and metabolism). In certain types of leukemia, part of one chromosome may be attached to part of a different chromosome. This change, called a translocation, can usually be detected under a microscope. Recognizing these translocations helps in identifying certain types of ALL and AML and is important in determining prognosis. Some types of leukemia have an abnormal number of chromosomes. For example, ALL cells with over 50 chromosomes are more sensitive to chemotherapy, and those with less than 46 are more resistant to it.

Molecular genetic studies: Certain substances, called antigen receptors, occur on the surface of lymphocytes. These receptors are important in initiating a response from the immune system. Normal lymphoid cells have many different antigen receptors which help the body respond to many types of infection. Lymphocytic leukemias, such as ALL, however, start from a single abnormal lymphocyte, so all the cells in each patient's leukemia have the same antigen receptor. Laboratory tests of the DNA sequences that contain information on each cell's antigen receptors are a very sensitive way to diagnose ALL. Because different subtypes of ALL cells have different antigen receptor features, this test is sometimes helpful in ALL classification. However, the test is quite complex and expensive, and it is not necessary in most cases.

Molecular genetic studies

Tests of leukemia cell DNA can also detect most translocations that are visible under a microscope in cytogenetic tests. DNA tests such as polymerase chain reaction (PCR) or fluorescent in situ hybridization (FISH), can also find some translocations involving parts of chromosomes too small to be seen with usual cytogenetic testing under a microscope. This sophisticated testing is sometimes helpful in leukemia classification because many subtypes of ALL and AML have distinctive translocations. Information about these translocations 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.

Imaging Studies

X-rays: A chest x-ray and bone x-ray are frequently obtained to diagnose and evaluate a child with leukemia. These may show a mass in the chest, or evidence that the leukemia has caused changes in the bone or, rarely, the joint.

Ultrasound: This test uses sound waves which, when reflected by organs, allow a mass or other abnormalities to be detected. It is useful in determining if the leukemia involves the kidney, spleen, or liver.

Computed tomography (CT scan): This is a special x-ray procedure, in which the x-ray beam moves around the body, taking pictures from different angles. A computer combines these views to produce a cross-sectional picture of the inside of the body.

Magnetic resonance imaging (MRI): This procedure uses large magnets and radio waves to produce computer-generated pictures of internal organs. The pictures look very similar to a CT scan but are more detailed. MRI will be used when there is concern about leukemia involving the brain.

Gallium scan and bone scan: For this procedure, the radiologist injects a radioactive chemical that accumulates in areas of cancer or infection in the body. This area can then be viewed with a special camera. These tests are useful when a patient has bone pain that might be due to bone infection or cancer involving bones. If the patient has already been diagnosed with leukemia, there is no need for this study.