Tests for Chronic Myelomonocytic Leukemia (CMML)

Blood tests

The complete blood count (CBC) measures levels of different cells in the blood, such as red blood cells, white blood cells, and platelets. The CBC is often done with a differential count (or “diff”), which is a count of the different types of white blood cells in the blood sample. In a blood smear, some of the blood is put on a slide to see how the cells look under the microscope.

People with CMML have higher numbers of monocytes, (at least 500 per mm³), which are a type of white blood cell. They also often have low numbers of other white blood cells, red blood cells and/or blood platelets.

Some people with CMML have monoblasts (sometimes just called 'blasts') in their blood. Monoblasts are very early forms of monocytes. Normally, these cells are only found in the bone marrow. It's never normal to see blasts in the blood, and it's often a sign of a bone marrow problem.

Blood cells in people with CMML may also have certain changes in size, shape, or other features that can be seen with a microscope.

Other blood tests may be done to check for other possible causes of low blood counts, such as low levels of vitamin B12 and folate. Tests may also be done to look for other causes of a high white blood cell count, such as an infection.

Bone marrow tests

Samples of bone marrow are taken during a bone marrow aspiration and biopsy for testing. The samples are usually taken from the back of the pelvic (hip) bone. These tests are used to diagnose and classify the type of blood cancer you have. They may also be repeated later on to see if treatment is working or to see if the CMML is transforming into an acute leukemia.

For bone marrow aspiration, you lie flat on a table (either on your side or on your belly). After cleaning the skin over the hip, the surface of the bone is numbed with local anesthetic. A very thin needle is used to put in the numbing drug, which may cause a brief stinging or burning sensation. A long, hollow needle is then put into the bone, and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most people still feel some brief pain when the marrow is removed.

A bone marrow biopsy is usually done right after the aspiration. A small core of bone and marrow is removed with a wider needle that's pushed into the hip bone. The biopsy also cause some brief pain. Once the biopsy is done, pressure on the area will help prevent bleeding and bruising.

A pathologist (a doctor trained in the diagnosis of diseases using lab tests) examines the bone marrow samples with a microscope. Other doctors may look at the samples too.

Looking at the cells in the bone marrow

The doctors will look at the types and number of blood-forming cells in the bone marrow aspirate and biopsy. They will also check to see if the bone marrow shows signs of infections, cancer cells, or other disorders. They will examine the size and shape of the cells and determine whether the red cells contain iron particles or if the white blood cells contain granules (microscopic collections of enzymes and other chemicals that help them fight infections).

Measuring blasts

Tests will be done to measure the percentage of marrow cells that are blasts. Blasts are very early forms of blood cells that are made by bone marrow stem cells. Over time, blasts mature into normal blood cells. But in CMML, some of the blasts don't mature properly, so there may be too many blasts and not enough mature cells. For a diagnosis of CMML, there must be less than 20% blasts in the bone marrow. If there are more than 20% blasts in the bone marrow, a person has acute leukemia.

Cytogenetic testing

This test (sometimes called karyotyping) looks at the chromosomes inside the cells. Each cell should have 46 chromosomes (23 pairs).DNA, which makes up our genes, is packed into chromosomes.

Chromosome changes are fairly common in CMML cells, although there's no single chromosome change that everyone with CMML has. Sometimes pieces of chromosomes or even whole chromosomes are missing. CMML cells may also have extra copies of all or part of some chromosomes. Chromosome translocations (parts of chromosomes trade places with each other) may also be seen.

Chromosome testing can also help the doctors be sure that the problem isn’t a different type of leukemia. For example, in chronic myeloid leukemia or CML, the leukemia cells often have an abnormal chromosome caused by a certain translocation. This is called the Philadelphia chromosome or BCR/ABL1 fusion. If the Philadelphia chromosome is present, the diagnosis is CML, not CMML. Finding changes in certain other genes also makes it very unlikely that a person has CMML.

Cytogenetic testing can take several weeks because the bone marrow cells need time to grow in lab dishes before the chromosomes can be seen with a microscope.

Another test option for looking at chromosomes is fluorescence in situ hybridization (FISH). This test uses special fluorescent dyes that only attach to specific parts of chromosomes. It can find most chromosome changes (such as translocations and deletions) that can be seen with standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing. FISH is very accurate, and results are often available within a couple of days.

Other tests

Other bone marrow tests can help the doctor diagnose CMML and rule out other blood diseases. For example:

• Immunocytochemistry can be helpful in distinguishing CMML from other types of leukemia and from other diseases.
• Flow cytometry can be very helpful in diagnosing leukemias and lymphomas.
• Molecular genetic tests aren't usually needed to diagnose CMML, but they can still be helpful in some cases.

These tests can also be done on cells from blood. For more on these lab tests, see Tests Used on Biopsy and Cytology Samples to Diagnose and Classify Cancer.