Myelodysplastic Syndrome Facts

Myelodysplastic syndrome, or MDS, is not a single disease but comprises a group of diseases that affect the blood-forming stem cells. “Myelo” means bone marrow, and “dysplastic” means malformed, thus describing the presence of abnormal cells in the marrow.

Bone marrow, contained in the soft, spongy center of your bones, is the body’s blood-cell factory. In adults, marrow is active in the flat bones, such as the pelvis, breastbone (sternum), and skull, and in the vertebrae. The bone marrow stem cells generate other bone marrow cells, including those that circulate in your blood. Red blood cells (RBCs) carry oxygen. White blood cells (WBCs) fight infection. Platelets help to make the blood clot and stop bleeding.

In MDS, the abnormal or malfunctioning stem cells in the marrow appear to interfere with the production of healthy RBCs, WBCs, and platelets. They also create defective bone marrow cells, which then make abnormal RBCs, WBCs, and platelets. Usually people with MDS have plenty of cells in their marrow but not in their blood. One reason is that the cells being formed die off prematurely (by a mechanism we call apoptosis). As MDS evolves, there are two ways in which the disease develops. Either fewer and fewer cells are produced or survive, leading to problems such as anemia, increased risk of infection, and risk of severe bleeding. Alternatively, in about 20% to 40% of patients, MDS transforms into a disease that is indistinguishable from acute leukemia. Thus, while MDS is often not considered a cancer, MDS cells have all the characteristics of cancer cells, and leukemia (a cancer of the marrow and blood) can develop within months or years.

Subtypes of MDS

Each year about 15,000 to 20,000 people are diagnosed with MDS in the United States. At Seattle Cancer Care Alliance, we see about 200 patients every year who have MDS or related diseases.

Doctors divide MDS into subtypes based on factors such as:

• Whether you have low levels of RBCs, WBCs, or platelets (or low levels of more than one type of blood cell) in your blood.
• Whether your have blast cells in your blood or your bone marrow, and what percentage of the blood or marrow is made up of these blasts.
• Whether the marrow shows dysplasia in only one type of blood-making cell (unilineage dysplasia) or in more than one type of blood-making cell (multilineage dysplasia)
• Whether there are chromosome abnormalities in the marrow cells and, if so, which types of abnormalities.

Doctors also look at the surface of MDS cells to see whether the cells express certain antigens. Some of these antigens may cause responses from the patient’s own immune system.

These and other factors (for example, whether you need transfusions or not) may help your doctor decide which type of treatment may make the most sense for you and how aggressive your treatment should be.

Here is a list of MDS subtypes, according to the World Health Organization (WHO) system of MDS classification:

• Refractory anemia (RA).
• Refractory anemia with ringed sideroblasts (RARS). Ringed sideroblasts are one type of cells that are precursors to RBCs.
• Refractory cytopenia with multilineage dysplasia (RCMD). If a person has multilineage dysplasia and ringed sideroblasts, this is classified as RCMD-RS.
• Refractory anemia with excess blasts-1 (RAEB-1) and refractory anemia with excess blasts-2 (RAEB-2). RAEB-2 is similar to RAEB-1 but with a higher percentage of blasts in the blood and the marrow.
• Myelodysplastic syndrome, unclassified (MDS-U).
• MDS associated with isolated del(5q). The term “del(5q)” means that part of chromosome #5 is missing.
• View details of the WHO classification system.

Risk Factors

Doctors do not know what causes the cellular changes that lead to MDS. The following factors may increase the risk for the disease:

• Exposure to toxins, such as benzene, radiation, or certain solvents or pesticides, over many years
• Smoking
• Chemotherapy or radiation used to treat cancer

However, so far there has been no epidemiologic study in the United States to better define factors that are important in the development of the disease. Researchers at the SCCA and the Fred Hutchinson Cancer Research Center have recently initiated studies to compare people without MDS to people with MDS in order to learn more about factors that may increase risk for the disease. We invite all patients who have an opportunity to participate in those studies.

MDS is more common in men than women. Children can get MDS, usually on the background of some genetically determined disease. The incidence of MDS increases throughout adulthood, and it is most common after the age of 50. About 80 percent of people with MDS are over age 60. Advanced age sometimes complicates treatment of MDS because older people with MDS are more likely to have other health problems, too.

Symptoms

In the early stages, many patients with MDS have no symptoms. But a blood test may show reduced levels of red blood cells and maybe reduced white blood cells or platelets. Some patients have symptoms related to their low blood cell counts, such as:

• Fatigue
• Shortness of breath
• Pale skin
• Weakness
• Dizziness
• General malaise
• Easy bruising
• Unexplained bleeding
• Fever
• Infections that won’t resolve

Symptoms can range from mild to severe. One person with MDS may have different or more or less severe symptoms than another person with the same disease.

Diagnosis

To find out whether you have MDS, your doctor will first do a thorough physical exam and ask about your health history. Next the doctor will perform a series of blood tests to tell whether any blood cells are unhealthy and, if so, which type. Common blood tests include the following:

• Complete blood cell count, or CBC: determines how many cells of each type are circulating in the blood stream
• Peripheral blood smear: looks at the appearance of the blood cells
• Blood chemistry: looks for abnormalities in the blood, including certain enzymes, iron level, and others

For a definitive diagnosis, doctors will need to perform a bone marrow aspiration and sometimes also a bone marrow biopsy. For this purpose a small area of skin over the lower back (pelvis) is cleaned and numbed. Then a marrow needle is used to withdraw bone marrow. If a biopsy is performed, the doctor uses a different needle to punch out a small piece of the bone marrow (a marrow core). In either case, the sample will be examined under a microscope, to determine the presence and number of abnormal cells in the marrow. In addition, marrow cells will be examined for the presence of abnormal chromosomes (cytogenetics). Doctors use the number and type of chromosome abnormalities to help predict how the disease will progress and which types of treatment might be most effective. Chromosomes provide the instructions for how our cells function. Other tests may include flow cytometry (a computer analysis of cells) and additional studies, which are being developed to establish a more accurate diagnosis. Marrow findings, chromosome analysis and blood cell counts are considered in another classification system, called the International Prognostic Scoring System (IPSS), which has been helpful in determining a patient’s prognosis (that is, how fast we expect the disease to progress). The IPSS score considers three factors:

• Your percentage of bone marrow blasts (categorized as <5%, 5% to 10%, 11% to 20%, or 21% to 30%)
• Which, if any, chromosome abnormalities are in your marrow cells (categorized as good, intermediate, or poor)
• How many types of cytopenia (low blood cell counts) you have (from 0 if you have none to 3 if you have low RBCs, low WBCs, and low platelets). Your score tells your doctor which risk group you are in: low risk, intermediate risk level 1 (abbreviated Int-1), intermediate risk level 2 (abbreviated Int-2), or high risk.