Diagnosis

What to expect on the journey to a diagnosis

Getting a diagnosis is important as it tells your doctor if you have acute lymphoblastic leukemia as opposed to another condition. If an acute lymphoblastic leukemia diagnosis is made, it can be used to predict how quickly the disease might progress and how it may respond to certain treatments.

Diagnostic techniques can also show what subtype of acute lymphoblastic leukemia is present. Identifying the subtype increases the accuracy of the predictions that your doctor can make about the course and severity of disease.

At the doctors

If you or your child have certain symptoms, a visit to your doctors is advised. Identifying diseases early often makes them easier to manage and increases the chances of successful treatment.

During your appointment, you may be asked about your medical history and for a description of any changes that you may have noticed. Your doctor might perform a physical examination of any areas that are swollen, bleeding, or bruised, and check for possible signs of infection.

Depending on the outcome of this assessment, your doctor may also want to take a blood sample to perform some initial blood tests.

Initial blood tests

Chemical profile

• Reveals information about the health of the liver and kidneys.

Complete blood count

• Shows the number of each group of blood cells present (red blood cells, white blood cells, and platelets).

Blood smear

• Identifies changes in the appearance of cells under a microscope, which may indicate the presence of disease.

At the specialist

If your doctor feels that further tests are needed, a referral to a specialist may be made. This will most likely be a hematologist, a doctor who has undertaken specialist training in diseases of the blood. The hematologist will go over the results and may suggest that further tests are performed.

These tests may include:

Bone marrow aspiration and biopsy

A sample is taken from the spongy marrow in the middle of the bone, normally from the hip.

In the case of a bone marrow aspiration, the sample will be a liquid, whereas in a biopsy, a small section of bone filled with marrow will be collected.

Bone marrow is where many blood cells are produced. Taking a sample from here can allow a hematopathologist (a specialist who studies blood cell diseases by looking at samples of cells and other tissues) to see what type of cells are being made and in what proportions. Cells that look unusual can be spotted using this test and classified according to any changes seen.¹

Lumbar puncture

This test is used if there is a concern that the leukemia may have spread into the brain and spinal cord. It assesses the number of cells in the fluid that bathes these organs. It is performed by inserting a needle into the base of the spine and drawing out some fluid.²

Lab tests

Further laboratory tests may be performed on the blood and bone marrow samples to diagnose and/or determine the specific type of acute lymphoblastic leukemia.

Cytomorphology

• Reveals information about the type of cells present by exposing the cells to chemical dyes that only react with certain types of leukemia cells. This causes a color change that is visible under a microscope.²

Flow cytometry and immunohistochemistry

• Allows the identification of leukemia cells by detecting specific proteins (known as antigens) on the surface of your cells. Different types of cells have different proteins, and the identification of these markers show scientists what type of acute lymphoblastic leukemia cells (B, T, or mixed) are present in the sample. This can tell doctors what specific type of acute lymphoblastic leukemia is present.¹

Genetic testing

• Acute lymphoblastic leukemia comprises several distinct genetic subtypes, identifying which subtype is present can help doctors make a diagnosis and inform treatment decisions. Therefore, comprehensive genetic testing is now considered standard of care.
• A range of different techniques, such as karyotyping and fluorescence in situ hybridization (FISH), will be used to examine the leukemic cells for abnormalities affecting the chromosomes and/or genetics. This will help determine the genetic subtype of acute lymphoblastic leukemia.
• In the UK, patients with acute lymphoblastic leukemia are eligible for whole genome sequencing. This is the most comprehensive and advanced genetic test available. For more information about whole genome sequencing, visit the Genomics England website.

Further blood tests

There are some serious conditions associated with cancer that can occur. More blood tests may be performed to monitor for the conditions listed below, so that the best treatment can be provided as soon as possible.

Conditions screened for:

• You may be tested to see if blood is clotting within your blood vessels. This is a syndrome called disseminated intravascular coagulation and can be associated with acute lymphoblastic leukemia.
• Tumor lysis syndrome is an emergency condition that can occur spontaneously but normally happens following chemotherapy treatment. It can be tested for in the blood by measuring the levels of electrolytes and waste products such as urea.
• Active infections, which may occur due to the low level of functioning white blood cells.

Imaging

There are many different imaging methods used for diagnosis and staging of acute lymphoblastic leukemia. Some techniques are better at visualizing bone changes, whereas others focus on blood flow. Together these techniques can build up a comprehensive picture of what is happening in the body. While imaging is not essential for a diagnosis of acute lymphoblastic leukemia, it can be used to give a clearer picture of the health of the organs and show if the cancer has spread. This, in turn, can help predict the response to treatment. You may have one or several forms of imaging performed.

Ultrasound

This is good for looking at soft tissue and fluid within the body. It uses high frequency soundwaves to create a dynamic image. This may be used to check your liver, spleen, and lymph nodes. The function of the heart may also be checked using a specialized form of ultrasound called echocardiography.

Computed tomography (CT) scan

A method used to visualize what is going on within the body and spot any changes from normal that might indicate how far the cancer has spread. This scan also provides information on the health of multiple organs, particularly the head and chest.

Magnetic resonance imaging (MRI)

MRI allows monitoring of the blood movement and inflammation within the body, along with structural information, and it can identify areas of increased or decreased blood flow. Cancers are often able to increase their own blood supply. An MRI test can help locate a tumor within the body and see if it is all in one place or in multiple areas.

Like a CT scan, MRI can take pictures of the whole body from multiple angles. It uses magnetism and radio waves to capture an image.

Genetic tests

• Karyotyping, also known as cytogenetic analysis, looks at the chromosomes in a cell and checks them for abnormalities. Changes may be present that give physicians a clue about how the specific type of acute lymphoblastic leukemia will respond to treatment. A typical genetic technique is fluorescence in situ hybridization (FISH), which allows certain changes in DNA and chromosomes to be fluorescently labeled to show their presence within tissues or cell samples.
• Chromosomal abnormalities, and mutations in certain genes, can be detected by polymerase chain reaction (PCR). You may have heard about this test in connection with COVID-19, but it can be useful in diagnosing many types of disease. It is a method to detect even very small amounts of DNA from a cancer cell. This is done to determine the type of acute lymphoblastic leukemia, but also to estimate how many cancer cells are left in the body, which is known as minimal residual disease (MRD).³

Once you or your child has a diagnosis, some of these tests may be repeated to show how you are responding to treatment.