Diagnosing Acute Lymphoblastic Leukemia

Doctors at NYU Langone’s Perlmutter Cancer Center use the results of sophisticated blood and tissue tests to diagnose acute lymphoblastic leukemia, a cancer of the blood and bone marrow. Bone marrow, the soft tissue in the center of bones, is where blood cells are made.

In acute lymphoblastic leukemia, commonly known as ALL, bone marrow produces too many immature white blood cells, called lymphoblasts. Lymphoblasts usually develop into healthy lymphocytes, which fight infection. But in acute lymphoblastic leukemia, the lymphoblasts don’t mature. Instead, they multiply rapidly in bone marrow and interfere with all blood cell production. They can travel to the bloodstream, continuing to divide and spreading to various organs.

Excess lymphoblasts, also called leukemia cells, in the blood and bone marrow can cause several health problems. First, because these lymphoblasts don’t develop into healthy white blood cells and typically decrease the number of healthy white blood cells in the body, risk of developing bacterial, viral, and fungal infections increases.

Second, lowered levels of healthy red blood cells, which carry oxygen to tissues and organs, can lead to anemia. This condition results in fatigue, shortness of breath, and pale skin.

Third, high numbers of lymphoblasts can also reduce the level of platelets, the cells that help blood clot. This can lead to increased bleeding; for example, you may have more frequent nosebleeds or excess bleeding if you cut yourself. Lower platelet levels may also lead to petechiae—flat, red, pinpoint spots caused by bleeding under the skin.

When lymphoblasts spread to the bloodstream, they often invade other parts of the body, causing swelling in organs such as lymph nodes, the immune system glands that trap viruses and bacteria. People with acute lymphoblastic leukemia may have swollen lymph nodes on either side of the neck, above the collarbone, under the arms, or around the groin.

Lymphoblasts may also accumulate in and enlarge the spleen, an organ in the upper left part of the abdomen that filters old red blood cells from the blood. An enlarged spleen can press on the stomach and cause a feeling of fullness. The liver, which also filters blood, can become swollen as lymphoblasts collect there. A swollen spleen and liver may cause the abdomen to protrude.

Lymphoblasts can also travel to the brain and spinal cord, causing symptoms such as headaches, seizures, or balance problems.

Although the causes of acute lymphoblastic leukemia are not completely understood, the condition is more common in white men than in others. While the condition is more common in children, it can also occur in adults. The incidence of acute lymphoblastic leukemia after age 50 is rising.

To diagnose the condition, a doctor asks about your medical history and symptoms. He or she may conduct a physical exam to check for swelling in the lymph nodes, liver, or spleen. Several tests can also aid in diagnosing the disease.

Blood Tests

Blood tests allow a doctor to look for increased levels of young white blood cells and reduced levels of red blood cells and platelets. Your doctor also examines the size, shape, and maturity of the white blood cells and looks for abnormal cells such as lymphoblasts.

Bone Marrow Aspiration and Biopsy

Doctors usually conduct a bone marrow aspiration and biopsy to establish the diagnosis of acute lymphoblastic leukemia.

To perform an aspiration, your doctor uses a needle to withdraw liquid from the bone marrow in the back of the pelvis. For a biopsy, the doctor removes a piece of bone and solid marrow from the same area. A pathologist—a doctor who studies diseases in a laboratory—looks at the bone marrow tissue and fluid under a microscope to see if they contain a high number of lymphoblasts.

These procedures are performed together, using a local anesthetic, in the doctor’s office or in the hospital. You can go home the same day as the biopsy.

Molecular and Genetic Analysis

NYU Langone pathologists also perform sophisticated molecular and genetic tests on blood or bone marrow to confirm a diagnosis, to determine a subtype of the condition, or to target a treatment.

Pathologists may use special antibodies, the immune system proteins that help the body recognize foreign substances, to stain cells from the blood or marrow. The staining can reveal the presence of certain proteins on the surface of lymphoblasts, which allows the pathologist to determine the subtype of acute lymphoblastic leukemia.

One way doctors classify acute lymphoblastic leukemia is by the type of white blood cells it forms in—either B cells or T cells. B cells, or B lymphocytes, produce proteins called antibodies that can attack viruses, bacteria, and other foreign matter. T cells, or T lymphocytes, are white blood cells that help to organize an immune response and attack foreign matter in the body.

Doctors also perform tests to identify abnormal chromosomes in lymphoblasts, a process called cytogenetic analysis. Chromosomes consist of DNA, which carries the instructions for genes to make the cellular proteins necessary for the body to function. Healthy human cells have 23 pairs of chromosomes. Mutations or breaks in the genes can lead to uncontrolled growth and cancerous changes in cells. An understanding of chromosomal changes can guide doctors in predicting how well a person’s cancer may respond to certain therapies.

Pathologists often look for a genetic abnormality called a translocation. A translocation occurs when DNA from one chromosome changes places with DNA of another chromosome. In acute lymphoblastic leukemia, a translocation may occur between chromosome 9 and chromosome 22. In this DNA exchange, a gene called ABL from chromosome 9 fuses with a gene called BCR on chromosome 22, creating the BCR–ABL fusion gene. Another name for this is the Philadelphia chromosome.

The BCR–ABL fusion gene makes a protein that signals cells to grow and multiply rapidly, contributing to the development of acute lymphoblastic leukemia, as well as chronic myelogenous leukemia or acute myeloid leukemia. People who have the BRC–ABL fusion gene are at increased risk for cancer returning after treatment. However, they may benefit from targeted medications, which block the activity of the BCR–ABL protein.

Doctors can also test for other genetic changes that occur with acute lymphoblastic leukemia. This helps them understand what subtype of cancer is present, how well a person may respond to treatment, and whether he or she is at risk for a recurrence. Using this information, doctors develop the best treatment plan.

Tests to Determine If Leukemia Has Spread

Our doctors may also perform a number of tests to see if acute lymphoblastic leukemia has spread to areas that cannot be felt during a physical exam, such as the brain and spinal cord or the lymph nodes.

Lumbar Puncture

After diagnosing acute lymphoblastic leukemia, doctors may perform a lumbar puncture to see if the cancer has spread to the spinal cord or brain. During a lumbar puncture, which requires a local anesthetic, your doctor inserts a needle into the spinal canal through the lower back to withdraw a sample of cerebrospinal fluid, the liquid that surrounds the spinal cord and brain. A pathologist then checks the fluid under a microscope to see if it contains lymphoblasts.

CT Scans

A CT scan uses X-rays and a computer to create three-dimensional, cross-sectional images of the body. The test can determine whether acute lymphoblastic leukemia has spread to lymph nodes that a doctor cannot detect with a physical exam, or whether organs such as the spleen or liver have become swollen.

Your doctor may give you a contrast agent before the scan. It’s taken by mouth as a liquid or pill or given as an injection into a vein. The contrast agent travels throughout the body, enabling doctors to get a clear view of organs and blood vessels.