Tests for Myelodysplastic Syndromes

Some people have signs or symptoms that suggest they might have a myelodysplastic syndrome (MDS). If you have symptoms, your health care provider will get a complete medical history, focusing on your symptoms and when they began. You will also be examined for possible causes of your symptoms.

For other people, MDS might be suspected based on the results of blood tests that are done for another reason.

In either case, if MDS is suspected, you will likely need tests to look at your blood and bone marrow cells to see if you have MDS or some other health condition.

Blood cell counts and blood cell examination

The complete blood count (CBC) is a test that measures the levels of red blood cells, white blood cells, and platelets in your blood. 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.

Patients with MDS often have too few red blood cells (anemia). They may have shortages of white blood cells and blood platelets as well. Patients with some types of MDS might also have myeloblasts ("blasts") in the blood. These are very early forms of blood cells that are normally only found in bone marrow. Blasts in the blood are not normal and are often a sign of a bone marrow problem. Blood cells from MDS patients may also have certain abnormalities in size, shape, or other features that can be seen under the microscope.

Blood abnormalities may suggest MDS, but the doctor cannot make an exact diagnosis without examining a sample of bone marrow cells.

Other blood tests

The doctor may also order tests to check for other possible causes of low blood counts. For example, low levels of iron, vitamin B12, or folate can cause anemia. If one of these is found to be abnormal, a diagnosis of MDS is much less likely.  

Bone marrow tests

Bone marrow samples are obtained from a bone marrow aspiration and biopsy, tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone. These tests are used first for diagnosis and classification, and they may be repeated later to tell if the MDS is responding to treatment or is transforming into an acute leukemia.

For a bone marrow aspiration, the skin over the hip and the surface of the bone is numbed with 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 put into the bone. The biopsy may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.

Lab tests of bone marrow or blood samples

A pathologist (a doctor specializing in the diagnosis of diseases using laboratory tests) examines the bone marrow and blood samples under a microscope. Other doctors, such as a hematologist (a doctor specializing in medical treatment of diseases of the blood and blood-forming tissues), might review these as well.

The doctors will look at the size, shape, and other features of the cells. The percentage of cells in the bone marrow or blood that are blasts (very early forms of blood cells) is particularly important. In MDS, the blasts do not mature properly, so there may be too many blasts and not enough mature cells.

For a diagnosis of MDS, a patient must have less than 20% blasts in the bone marrow and blood. A patient who has more than 20% blasts is considered to have acute myeloid leukemia (AML).

Other types of lab tests can also be done on the bone marrow or blood samples to help diagnose MDS:

Flow cytometry and immunocytochemistry

For both flow cytometry and immunocytochemistry, samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For immunocytochemistry, the cells are then looked at under a microscope to see if the antibodies stuck to them (meaning they have these proteins), while for flow cytometry a special machine is used.

These tests can be helpful in distinguishing different types of MDS or leukemia from one another and from other diseases.

Chromosome tests

These tests look at the chromosomes (long strands of DNA) inside the cells. Each cell should have 46 chromosomes (23 pairs). Abnormal chromosomes are common in MDS (see below).

Cytogenetics: In this test, the cells are looked at under a microscope to see if the chromosomes have any abnormalities. A drawback of this test is that it usually takes about 2 to 3 weeks because the cells must grow in lab dishes for a couple of weeks before their chromosomes can be viewed.

The results of cytogenetic testing are written in a shorthand form that describes which chromosome changes are present. For example:

• A minus sign (-) or the abbreviation “del” is used to mean a deletion. For example, if a copy of chromosome 7 is missing, it can be written as -7 or del(7). Often, only a part of the chromosome is lost. There are 2 parts to a chromosome, called p and q. The loss of the q part of chromosome 5 is written 5q- or del(5q).
• A plus sign is used when there is an addition (an extra copy of all or part of a chromosome). +8, for example, means that chromosome 8 has been duplicated, and there are too many copies of it within the cell.
• The letter t is used to indicate a translocation, in which parts of two chromosomes have traded places with each other. For example, if chromosomes 8 and 21 have swapped pieces, it would be written as t(8;21)

Certain chromosome changes in MDS cells can help predict the likely course of MDS. For example, a deletion of a part of chromosome 5, or del(5q), usually predicts a better outcome (as long as there is no more than one other chromosome change, and it isn't a loss of part of chromosome 7). Changes in 3 or more chromosomes or the deletion of chromosome 7 tend to have a poorer outlook.

Fluorescent in situ hybridization (FISH): This test looks more closely at cell DNA using fluorescent dyes that only attach to specific gene or chromosome changes. An advantage of FISH is that it doesn’t require actively dividing cells, so it can usually provide results within a couple of days. FISH is very good for finding translocations – it can even find some that may be too small to be seen with usual cytogenetic testing.

Polymerase chain reaction (PCR): This is a very sensitive DNA test that can also find some chromosome changes too small to be seen under a microscope, even if there are very few abnormal cells in a sample.

Other molecular and genetic tests

Other types of lab tests can also be done on the samples to look for specific gene or other changes in the MDS cells. This is sometimes referred to as biomarker testing.

For example, the MDS cells are tested for changes (mutations) in genes such as IDH1. People whose MDS cells have changes in this gene are more likely to be helped by treatment with certain targeted therapy drugs.