Testing for Leukemia: Getting a Leukemia Diagnosis

Leukemia is a cancer of the blood-forming tissues that often develops in the bone marrow. It affects cells that develop into blood cells, such as red blood cells, white blood cells, and platelets. The most common signs of leukemia include fevers, fatigue, bleeding, and bruising.

If your healthcare provider suspects that you have leukemia, they will refer you to an oncologist (a medical doctor who specializes in diagnosing and treating cancer). Diagnostic tests include blood tests, imaging studies, bone marrow tests, and spinal fluid tests. 

The first step in diagnosing leukemia is a thorough physical exam and review of your medical history. Your healthcare provider will ask several questions about your symptoms and overall health. Common signs of leukemia include fatigue, fevers, bleeding, and bruising. 

During the physical exam, your provider will check your eyes, mouth, and skin. They will feel your lymph nodes, liver, and spleen to look for signs of inflammation. Your provider will also examine any areas of bleeding or bruising.

Leukemia changes the amount and health of cells in the blood. This cancer often develops in the bone marrow, the soft inner part of the bones. Bone marrow is made up of blood-forming cells, fat cells, and other tissues.

When cancer cells form in the bone marrow, they crowd out the healthy cells. This affects the following types of blood cells:

• Red blood cells (RBCs): Cells that carry oxygen from the lungs to other tissues
• White blood cells (WBCs): Immune system cells that help the body fight infections
• Platelets: Cell fragments that plug holes in the blood vessels to prevent bleeding

The following blood tests may help diagnose leukemia:

• Peripheral smear (blood smear): A hematologist (a medical doctor specializing in blood disorders) reviews a sample of your blood under a microscope to look for abnormalities in the appearance and number of blood cells.
• Complete blood count (CBC): This measures the amounts of red blood cells, white blood cells, and platelets. A lack of red blood cells and platelets may indicate leukemia. People with leukemia often have a high number of immature white blood cells called myeloblast, which are not usually present in the blood. 
• Comprehensive metabolic panel (CMP): This measures blood sugar (glucose) and certain minerals, electrolytes, and proteins. It can help determine whether cancer cells have affected the liver and kidneys. 
• Liver function tests (LFTs): These tests measure substances made by the liver. 
• Coagulation panel: This panel measures proteins in the blood to determine how well the blood can clot. It includes a fibrinogen test, which measures levels of blood-clotting proteins called fibrinogens.

Imaging tests use X-rays, sound waves, magnetic fields, or radioactive particles to provide images of the inside of the body. Although leukemia does not cause solid tumors, an imaging test may help determine if it has caused complications or infections. 

Imaging tests for leukemia diagnosis include:

• X-ray: A chest X-ray can determine if you have a lung infection; leukemia affects the immune system and raises the risk of infection.
• Computed tomography (CT) scan: A CT scan uses X-rays to create images of the body. It can determine whether the lymph nodes are enlarged. Healthcare providers may also use CT scans to guide a needle biopsy. 
• Magnetic resonance imaging (MRI): An MRI uses radio waves and strong magnets to provide detailed images of the body’s soft tissues. It can determine if leukemia has affected the brain and spinal cord.
• Positron emission tomography (PET) scan: A PET scan detects cancer cells and determines how far they have spread. It involves injecting glucose containing a radioactive atom into the blood. Cancer cells absorb large amounts of sugar, absorbing the radioactive material. A special camera can create images of these cells. 
• Ultrasound: This noninvasive test uses sound waves and echoes to produce pictures of internal organs. It can help determine if the lymph nodes are swollen. 

The bone marrow is the soft inner part of certain bones where new cells are produced. Leukemia often develops in the bone marrow. 

Bone marrow tests to diagnose leukemia include:

• Bone marrow aspiration: During an aspiration, your healthcare provider will take a sample of the bone marrow using a thin, hollow needle from the back of the hip (pelvic) bone. 
• Bone marrow biopsy: After an aspiration, your provider may take a small piece of bone and marrow using a slightly larger needle pushed down to the bone. 

For both of these tests, your healthcare provider will numb the area of the body using a local anesthetic. Even though the skin and tissues are numbed for these tests, they usually cause brief pain.

Cytochemistry refers to exposing cells to chemical stains or dyes and observing the reaction. Certain leukemia cells react to these chemicals and cause color changes in the cells. This can help determine if a person has leukemia and which type they have. 

Cytochemistry tests for leukemia include:

• Flow cytometry and immunohistochemistry: This test identifies leukemia cells by treating them with certain antibodies (defense proteins produced by the immune system) and examining them under a microscope. 
• Chromosome and gene tests: These tests examine the chromosomes inside cells. Chromosomes are the long strands of DNA that contain genes. Certain types of leukemia change the appearance of chromosomes under a microscope. 

Cerebrospinal fluid (CSF) surrounds and cushions the brain and spinal cord. If your healthcare provider is concerned that leukemia cells have spread to your brain or spinal cord, they may recommend a test known as a lumbar puncture or spinal tap.

During this test, your provider uses a small hollow needle to take a sample of spinal fluid. The sample is then sent to the lab, where a pathologist examines it under a microscope. A pathologist is a medical doctor who analyzes body samples, such as fluid and tissues, to help diagnose a condition and determine the best treatment. 

Once you are diagnosed with leukemia, your healthcare team will conduct further testing to determine the cancer’s stage, or how advanced it is.

Leukemia does not cause solid tumors like other cancers, and its staging process differs from most other cancers. Different types of leukemia have different staging processes. 

Healthcare providers in the United States typically use the Rai system to stage chronic lymphocytic leukemia (CLL). This system is based on the number of lymphocytes (white blood cells) in the blood and bone marrow. Rai system stages include:

• Stage 0: High number of lymphocytes in blood or bone marrow; normal red blood cell and platelet levels; no enlargement of the lymph nodes, spleen, or liver
• Stage 1: High number of lymphocytes; normal red blood cell and platelet levels; enlarged lymph nodes
• Stage 2: High number of lymphocytes; normal red blood cell and platelet levels; enlarged liver or spleen with or without swollen lymph nodes
• Stage 3: High number of lymphocytes; normal platelet levels; low red blood cell count (anemia); with or without enlarged lymph nodes, spleen, or liver
• Stage 4: High number of lymphocytes; low platelet levels; with or without low red blood cell count (anemia); with or without enlargement of the lymph nodes, spleen, or liver

Chronic myeloid leukemia (CML) is classified by phases rather than stages. The phases are based on the number of immature myeloid cells in the blood and bone marrow. Phases of CML include:

• Chronic phase: Earliest phase; less than 10% immature cells (blasts) in the blood or bone marrow; there may be no signs or symptoms
• Accelerated phase: Between 10-19% blasts in the blood or bone marrow; symptoms may include fever and unintended weight loss
• Blast phase: Most aggressive phase; 20% or more blasts in the blood or bone marrow; possible symptoms include fever, fatigue, and an enlarged spleen

Some diseases and chronic health conditions cause many of the same signs and symptoms as leukemia. Once you develop symptoms such as fatigue and fevers, your healthcare team will run several tests to rule out other possible causes. 

Conditions that may cause the same symptoms as leukemia include:

• Viral infections: Certain viruses like Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) affect white blood cell counts and cause an increase in immature white blood cells in the bloodstream.
• Myeloproliferative disorders: These conditions affect immature bone marrow cells and may cause the same symptoms as leukemia. Examples include polycythemia vera and essential thrombocytosis. 
• Aplastic anemia: This chronic condition causes the bone marrow to stop producing blood cells. Symptoms include frequent infections and bleeding. 
• Myelodysplastic syndromes: These chronic conditions affect the bone marrow and may raise the risk of leukemia. 

Leukemia is a cancer of the blood-forming tissues in the body. Common signs of leukemia include fever, fatigue, frequent infections, bleeding, and bruising. 

Several medical tests are used to diagnose leukemia. Your healthcare provider will likely start with a physical exam, medical history, and blood tests. Additional tests include bone marrow aspiration and biopsy, imaging studies, and cytochemistry. 

Once a person is diagnosed with leukemia, their healthcare team conducts more tests to determine the stage, which is needed to develop an appropriate treatment plan.