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Certain signs and symptoms can suggest that a person might have acute lymphocytic leukemia (ALL), but tests are needed to confirm the diagnosis.
If you have signs and symptoms that suggest you might have leukemia, the doctor will want to get a thorough medical history, including how long you have had symptoms and if you have possibly been exposed to anything considered a risk factor.
During the physical exam, the doctor will probably focus on 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 thorough nervous system exam may be done. Your abdomen will be felt for spleen or liver enlargement.
If there is reason to think low levels of blood cells might be causing your symptoms (anemia, infections, bleeding or bruising, etc.), the doctor will most likely order blood tests to check your blood cell counts. You might also be referred to a hematologist, a doctor who specializes in diseases of the blood (including leukemia).
If your doctor thinks you might have leukemia, they will need to check samples of cells from your blood and bone marrow to be sure. Other tissue and cell samples may also be taken to help guide treatment.
Blood samples for ALL tests are generally taken from a vein in the arm.
Complete blood count (CBC) and peripheral blood smear: The CBC measures the numbers of red blood cells, white blood cells, and platelets. This test is often done along with a differential (or diff) which looks at the numbers of the different types of white blood cells. These tests are often the first ones done on patients with a suspected blood problem.
For the peripheral blood smear (sometimes just called a smear), a drop of blood is smeared across a slide and then looked at under a microscope to see how the cells look. Changes in the numbers and the appearance of the cells often help diagnose leukemia.
Most patients with ALL have too many immature white cells called lymphoblasts (or just blasts) in their blood, and not enough red blood cells or platelets. Lymphoblasts are not normally found in the blood, and they don't function like normal, mature white blood cells.
Even though these findings may suggest leukemia, the disease usually is not diagnosed without looking at a sample of bone marrow cells.
Blood chemistry tests: Blood chemistry tests measure the amounts of certain chemicals in the blood, but they are not used to diagnose leukemia. In patients already known to have ALL, these tests can help detect liver or kidney problems caused by spreading leukemia cells or the side effects of certain chemotherapy drugs. These tests also help determine if treatment is needed to correct low or high blood levels of certain minerals.
Coagulation tests: Blood coagulation tests may be done to make sure the blood is clotting properly.
Leukemia starts in the bone marrow, so checking the bone marrow for leukemia cells is a key part of testing for it.
Bone marrow aspiration and biopsy: Bone marrow samples are obtained by bone marrow aspiration and biopsy – tests usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the sternum (breastbone) or other bones.
In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the skin and the surface of the bone by injecting a local anesthetic, which may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most patients still have some brief pain when the marrow is removed.
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. With local anesthetic, most patients just feel some pressure and tugging from the biopsy, but some may feel a brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.
These bone marrow tests are used to help diagnose leukemia. They may also be done again later to tell if the leukemia is responding to treatment.
One or more of the following lab tests may be done on the samples to diagnose AML and/or to determine the specific subtype of ALL.
Routine exams with a microscope: The bone marrow (and sometimes blood) samples are looked at with a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in cancer and blood diseases).
The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types.
A key factor is whether the cells look mature (like normal blood cells), or immature (lacking features of normal blood cells). The most immature cells are called lymphoblasts (or just blasts).
Determining what percentage of cells in the bone marrow are blasts is particularly important. A diagnosis of ALL generally requires that at least 20% of the cells in the bone marrow are blasts. Under normal circumstances, blasts don't make up more than 5% of bone marrow cells.
Sometimes just counting and looking at the cells doesn’t provide a definite diagnosis, and other lab tests are needed.
Cytochemistry: In cytochemistry tests, cells are put on a slide and exposed to chemical stains (dyes) that react only with some types of leukemia cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present. For instance, one stain will turn parts of acute myeloid leukemia (AML) cells black, but has no effect on ALL cells.
Flow cytometry and immunohistochemistry: For both flow cytometry and immunohistochemistry, samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For immunohistochemistry, the cells are examined under a microscope to see if the antibodies stuck to them (meaning they have those proteins), while for flow cytometry a special machine is used.
These tests are used for immunophenotyping – classifying leukemia cells according to proteins on or in the cells. This kind of testing is very helpful in determining the exact type of leukemia. For diagnosing 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 ALL, these tests are most often used to help determine the exact subtype of in someone already thought to have ALL based on other tests.
These tests look at the chromosomes (long strands of DNA) inside the cells. Normal human cells contain 23 pairs of chromosomes (bundles of DNA). In ALL, the cells sometimes have chromosome changes. Recognizing these changes can help identify certain types of ALL, and it can be important in determining a patient’s outlook and likely response to some treatments. For this reason, chromosome testing is a standard part of the work-up for ALL.
The most common chromosome change in ALL is a translocation, in which, 2 chromosomes swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. The most common chromosome change in adult ALL is a translocation that results in a shortened chromosome 22 (called the Philadelphia chromosome). About 1 out of 4 adults with ALL have this abnormality in their leukemia cells. This change is especially important because it can be targeted with certain drugs.
Cytogenetics: For this test, the cells are grown in lab dishes until they start dividing. Then the chromosomes are looked at under a microscope to detect any changes.
Because it takes time for the cells to start dividing, cytogenetic testing often takes about 2 to 3 weeks.
Not all chromosome changes can be seen under a microscope. Other lab tests can often help find 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 genes or 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 on regular blood or bone marrow samples. Because the cells don’t have to be able to divide for this test, it can also be used to look at cells from other tissues, like lymph node samples. It is very accurate and can usually provide results within a couple of days. But because FISH only tests for certain gene changes (and doesn’t look at the chromosomes overall), it is best for looking for the changes that are important based on the kind of leukemia a person has.
Polymerase chain reaction (PCR): This is a very sensitive DNA test that can also find certain gene and chromosome changes too small to be seen with a microscope, even if very few leukemia cells are present in a sample. Like FISH, it is used to find particular gene changes and not to look at the chromosomes overall.
If the leukemia cells have a particular gene (or chromosome) change, PCR can be used after treatment to try to find small numbers of leukemia cells that may not be visible with a microscope.
Other molecular and genetic tests
Other, newer types of lab tests can also be done on the samples to look for specific gene or other changes in the leukemia cells.
ALL can spread to the area around the brain and spinal cord. To check for this spread, doctors remove a sample of the fluid from that area (cerebrospinal fluid or CSF) for testing.
You may lay on your side or sit up for this test. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine and into the area around the spinal cord to collect some fluid.
A lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.
A lymph node or part of a lymph node is often removed to help diagnose lymphomas, but this is only rarely needed with leukemia because the diagnosis is usually made looking at blood and bone marrow.
In this procedure, a surgeon cuts through the skin to remove all or part of a lymph node. If the node is just under the skin, this is a simple operation that can often be done with local anesthesia, but if the node is inside the chest or abdomen, general anesthesia is used to keep you asleep during the biopsy.
When the entire lymph node is removed, it is called an excisional lymph node biopsy. If only part of the lymph node is removed, it is called an incisional lymph node biopsy.
Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to create pictures of the inside of the body. Leukemia does not usually form tumors, so imaging tests aren’t as useful as they are for other types of cancer. Imaging tests might be done in people with ALL to help determine the extent of the disease, if it is thought to have spread beyond the bone marrow and blood. They might also be done to look for infections or other problems. .
Chest x-rays may be done if the doctor suspects a lung infection. They may also be done to look for enlarged lymph nodes in the chest.
The CT scan uses x-rays to make detailed, cross-sectional images of your body.
This test can show if any lymph nodes or organs in your body are enlarged. It isn’t usually needed to diagnose ALL, but it may be done if your doctor suspects leukemia cells are growing in an organ, like your spleen.
Sometimes a test that combines the CT scan with a PET (positron emission tomography) scan (PET/CT scan) is done. This is not often needed for patients with ALL.
MRI scans make detailed images of the body using radio waves and strong magnets instead of x-rays. They are very helpful in looking at the brain and spinal cord. This test might be done if a lumbar puncture finds leukemia cells in the CSF, or if a person is having symptoms that could mean the ALL has spread to the area around the brain.
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 also be used to look at the testicles, if needed.
This is an easy test to have, and it uses no radiation.
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Appelbaum FR. Chapter 98: Acute Leukemias in Adults. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa. Elsevier: 2014.
Jain N, Gurbuxani S, Rhee C, Stock W. Chapter 65: Acute Lymphoblastic Leukemia in Adults. In: Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa: Elsevier; 2013.
National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia. V.1.2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/all.pdf on July 23, 2018.
Last Revised: October 17, 2018