Tests for Childhood Leukemia

Most of the signs and symptoms of childhood leukemia are more likely to have other causes, such as infections. Still, it’s important to let your child’s doctor know about such symptoms right away so that the cause can be found and treated, if needed.

Exams and tests will be done to determine the cause of the symptoms. If leukemia is found, further tests will be needed to find out the type and subtype of leukemia and decide how it should be treated.

It’s 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.

Medical history and physical exam

If your child has signs and symptoms that suggest they might have leukemia, the doctor will want to get a thorough medical history to learn about the symptoms and how long your child has had them. The doctor may also ask about exposure to possible risk factors. A family history of cancer, especially leukemia, may also be important.

During the physical exam, the doctor will look for 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 nervous system exam may be done. The child's abdomen (belly) will be felt for signs of an enlarged spleen or liver.

Tests to look for leukemia in children

If the doctor thinks your child might have leukemia, blood and bone marrow samples will need to be checked to be sure. Your child’s doctor may refer you to a pediatric oncologist, a doctor who specializes in childhood cancers (including leukemias), to have some of these tests done. If leukemia is found, other types of tests may also be done to help guide treatment.

Blood tests

The first tests done to look for leukemia are blood tests. The blood samples are usually taken from a vein in the arm, but 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 blood cells of each type are 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 blood cells and changes in the way these cells look may make the doctor suspect leukemia.

Most children with leukemia 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 can’t be diagnosed for sure without looking at a sample of bone marrow cells.

Bone marrow aspiration and biopsy

A bone marrow aspiration and bone marrow biopsy are tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bones, but sometimes they may be taken from the front of the pelvic bones or from other bones.

Before the tests, the skin over the hip bone is cleaned and numbed by injecting a local anesthetic or applying a numbing cream. In most cases, the child is also given other medicines to make them drowsy or even go to sleep during the tests.

• For a bone marrow aspiration, 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 pushed down into the bone. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding.

The bone marrow samples are then sent to a lab for testing.

Bone marrow tests are used to diagnose leukemia, but they may also be repeated later to find out 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 applies a numbing cream in an area in the lower part of the back over the spine. The doctor usually also gives the child medicine to make them sleep during the procedure. A small, hollow needle is then put in between the bones of the spine to withdraw some of the fluid, which is then sent to a lab for testing.

In children already diagnosed with leukemia, lumbar punctures might 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. (This is known as intrathecal chemotherapy.)

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 (known as an excisional biopsy). If the node is near the skin surface, this is a simple operation. But it is more complex if the node is inside the chest or abdomen. Most often the child will need general anesthesia (where the child is asleep).

Lab tests to diagnose and classify leukemia

All blood, bone marrow, and other samples are sent to a lab for further testing.

Microscopic exams

All of the samples taken (blood, bone marrow, lymph node tissue, or CSF) are looked at with a microscope. The samples might be exposed to chemical stains (dyes) that can cause color changes in some types of leukemia cells.

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.

Flow cytometry and immunohistochemistry

These tests are used to classify leukemia cells based on certain proteins in or on the cells (known as immunophenotyping). This kind of testing is very helpful in determining the exact type and subtype of leukemia. It is most often done on cells from bone marrow, but it can also be done on cells from the blood, lymph nodes, and other body fluids.

For both flow cytometry and immunohistochemistry, samples of cells are treated with antibodies, which are proteins that stick to certain other proteins on cells. For immunohistochemistry, the cells are then examined under a microscope to see if the antibodies stuck to them (meaning they have these proteins), while for flow cytometry a special machine is used.

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 more DNA than normal (a DNA index of 1.16 or higher) are often more sensitive to chemotherapy, and these leukemias have a better prognosis (outlook).

Flow cytometry can also be used to measure the response to treatment and the existence of minimal residual disease (MRD) in some types of leukemias. (See Prognostic Factors in Childhood Leukemia.)

Chromosome tests

These tests look at the chromosomes (long strands of DNA) inside the cells. Normal human cells have 23 pairs of chromosomes, each of which is a certain size and looks a certain way under the microscope. But in some types of leukemia, the cells have changes in their chromosomes.

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. Other types of chromosome changes are also possible. Recognizing these changes can help identify certain subtypes of acute leukemias and can help determine prognosis (outlook).

Sometimes the leukemia cells have 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 child’s outlook. For example, in ALL, chemotherapy is more likely to work if the cells have more than 50 chromosomes and is less likely to work if the cells have fewer than 46 chromosomes.

Finding these types of chromosome changes with lab tests can be very helpful in predicting a child’s outlook and response to treatment.

Cytogenetics: For this test, leukemia cells are grown in a lab dish and the chromosomes are looked at under a microscope to detect any changes, including missing or extra 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.

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 another way to look at chromosomes and genes. 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 test that can also find some chromosome and gene changes too small to be seen under a microscope, even if there are very few leukemia cells in a sample. This test can be very useful in looking for small numbers of leukemia cells (minimal residual disease, or MRD) that might not be detected with other tests during and after treatment.

Other molecular and genetic tests: Newer types of lab tests, sometimes called next generation sequencing (NGS) tests, can also be done on the samples to look for specific gene changes in the leukemia cells.

Other blood tests

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

These tests aren’t 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 make sure the blood is clotting properly.

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

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to make pictures of the inside of the body. Leukemia doesn’t 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 these tests to get a better idea of the extent of the disease or to look for other problems, such as infections. For more details, see Imaging Tests.

Chest x-rays

A chest x-ray can help detect an enlarged thymus or lymph nodes in the chest. If the test result is abnormal, a computed tomography (CT) scan of the chest may be done to get a more detailed view.

Chest x-rays can also help look for pneumonia if your child might have a lung infection.

Computed tomography (CT) scan

The CT scan isn’t usually needed for children with leukemia, but it might 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 an MRI scan may also be used for this.

PET/CT scan: Some machines combine the CT scan with a positron emission tomography (PET) scan, which can provide more information about any abnormal areas that appear on the CT.

Magnetic resonance imaging (MRI) scan

An MRI scan, like a CT scan, makes detailed images of soft tissues in the body. It’s most helpful in looking at the brain and spinal cord, so it’s most likely to be done if the doctor has reason to think the leukemia might have spread there (such as if the child has symptoms like headaches, seizures, or vomiting). This test doesn’t expose the child to radiation.

Ultrasound

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 a fairly easy test to have, and it uses no radiation.