Diagnosis of childhood leukemia

Diagnosis is the process of finding out the cause of a health problem. Diagnosing childhood leukemia usually begins with a visit to your family doctor or when a blood test suggests a problem with the blood. The doctor will ask about any symptoms your child has and do a physical exam. Based on this information, the doctor will refer your child to a specialist or order tests to check for leukemia or other health problems.

The process of diagnosis may seem long and frustrating. It’s normal to worry, but try to remember that other health conditions can cause similar symptoms as leukemia. It’s important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of childhood leukemia.

The following tests are usually used to rule out or diagnose childhood leukemia. Many of the same tests used to diagnose cancer are used to find out whether the leukemia has spread to other parts of the body, such as the brain or testicles. The doctor may also order other tests to check your child’s general health and to help plan treatment.

Your child’s health history is a record of symptoms, risks and all the medical events and problems your child has had in the past. The doctor will ask questions about your child’s personal or family history of certain genetic conditions, including:

• Down syndrome
• Bloom syndrome
• Fanconi anemia
• ataxia-telangiectasia (AT)
• neurofibromatosis type 1 (von Recklinghausen disease)
• Wiskott-Aldrich syndrome
• Klinefelter syndrome
• Li-Fraumeni syndrome
• Shwachman-Diamond syndrome

A physical exam allows the doctor to look for any signs of childhood leukemia. During a physical exam, the doctor may:

• measure vital signs to check for fever, shortness of breath and rapid heartbeat
• check the skin for bruising and paleness
• feel areas of the neck, underarms and groin for any swollen or larger than normal lymph nodes
• check the mouth for infection, bleeding or swollen gums
• check the testicles for swelling
• feel the abdomen for a larger than normal liver or spleen
• check the skeleton for tenderness or pain

Find out more about physical exams.

A complete blood count (CBC) measures the number and quality of white blood cells, red blood cells and platelets. A CBC is done to see how well the bone marrow is working and to check for anemia. Childhood leukemia may be suspected if:

• the blood cell counts are outside normal ranges
• there are immature blood cells (blasts) in the blood (blasts are normally only found in the bone marrow)
• the white blood cell (WBC) count is low or high
• the number of platelets is low

Find out more about complete blood counts.

Leukemia can cause abnormal levels of blood clotting factors, which can affect how well the body can clot blood. The following tests may be done to measure blood clotting factors:

• fibrinogen level
• prothrombin time (PT) or international normalized ratio (INR)
• partial thromboplastin time (PTT)

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are working and can help find abnormalities. They may be used to set a baseline before treatment for leukemia begins. The following blood chemistry tests may be checked when your child’s doctor suspects a diagnosis of leukemia.

Blood urea nitrogen (BUN) and creatinine may be measured to check how well the kidneys are working.

Alanine aminotransferase (ALT), aspartate transaminase (AST) and alkaline phosphatase are liver enzymes that are measured to check how well the liver is working.

Lactate dehydrogenase (LDH) may be measured to check for increased cell turnover. LDH may be high due to leukemia or other conditions.

Phosphate levels in blood may be measured to check for problems with the kidneys, liver or bone.

Uric acid levels in the blood may be higher than normal with leukemia or other conditions.

Electrolytes, such as sodium and potassium, may be measured as part of routine testing and can be used to check for other conditions. Potassium levels may be higher than normal with leukemia.

Find out more about blood chemistry tests.

There are several tests used for molecular and genetic testing.

Immunophenotyping is the study of proteins expressed by cells. It is used to determine the type or subtype of leukemia. Immunophenotyping uses a very specific antigen-antibody reaction to identify proteins in tissues or cells. It uses monoclonal antibodies marked with a fluorescent or specific enzyme label that binds only to specific antigens (proteins). The fluorescent or enzyme label allows doctors to see the blasts.

Immunohistochemistry is used in immunophenotyping. It uses a microscope to view the fluorescent labels. It also allows doctors to look at cells and what is around them.

Flow cytometry is a method involved in immunophenotyping. It involves using a special machine to sort and classify cells using fluorescent labels on their surface. It allows doctors to view many antibodies at the same time. The cells are exposed to a laser, which makes the cells give off a light that is measured and analyzed by a computer. It allows data to be collected rapidly from thousands of cells in a single sample. Flow cytometry helps define unique features of leukemia cells and can distinguish between B-cell ALL, T-cell ALL and AML. This helps doctors make a diagnosis and treatment plan. Flow cytometry can be used to measure response to treatment using minimal residual disease (MRD). Flow cytometry can detect blasts in the bone marrow with greater sensitivity than microscopy.

Cytogenetics looks at a cell’s chromosomes under a microscope to assess the number, size, shape and arrangement. Cytogenetic techniques show chromosomal abnormalities, which help doctors confirm the diagnosis and identify the type or subtype of leukemia. The results of cytogenetic studies also help doctors plan treatment and predict how well the treatment will work.

Fluorescence in situ hybridization (FISH) uses special DNA probes labelled with fluorescent dyes to identify chromosomal abnormalities and other genetic changes in the leukemia cells. FISH is used to diagnose types of leukemia that look the same but have different genetic abnormalities and may need to be treated differently. It is a molecular genetic test used to identify chromosomal abnormalities and other genetic changes in the blasts.

Polymerase chain reaction (PCR) makes many copies of a particular gene segment so that it can be tested in the lab. PCR is used to find DNA mutations, inversions or deletions that are associated with certain types of leukemia. It may be useful in diagnosing and determining the prognosis for specific types of leukemia. PCR may also be used to detect MRD in certain types of leukemia with a specific genetic abnormality that can be followed during treatment.

An x-ray uses small doses of radiation to make an image of parts of the body on film. It is used to check:

• the child’s airway before sedation for bone marrow aspiration and biopsy
• for a lung infection
• for a larger than normal thymus
• for larger than normal lymph nodes in the chest (mediastinal mass)

Find out more about x-rays.

A lumbar puncture (spinal tap) involves removing a small amount of cerebrospinal fluid (CSF) from the spine. CSF is the fluid that surrounds and helps protect the brain and spinal cord. The CSF fluid removed during a lumbar puncture is looked at under a microscope to see if cancer has spread to the central nervous system (CNS).

Find out more about lumbar punctures.

A bone marrow aspiration and biopsy removes cells from the bone marrow so that they can be tested in a lab. The results of the bone marrow aspiration and biopsy will confirm whether or not the child has leukemia.

The samples collected during bone marrow aspiration can also be used for other tests, such as immunophenotyping by flow cytometry and chromosome and molecular genetic analyses. These tests help doctors identify the type of leukemia and plan the best treatments for the child.

Find out more about bone marrow aspiration and biopsy.

To make the decisions that are right for your child, ask the healthcare team questions about a diagnosis.