Myelodysplastic Syndrome Facts

Myelodysplastic syndrome (MDS) is not a single disease but a group of diseases that affect blood cell formation. In all forms of MDS, a bone marrow problem leads to low levels of blood cells circulating in the blood. “Myelo” refers to bone marrow, which is the body’s blood-cell factory. “Dysplastic” refers to abnormal growth or development. “Myelodysplastic,” therefore, refers to the fact that the bone marrow produces abnormal blood cells.

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.

Healthy Blood Cell Formation
 

In a healthy body, the stem cells in the bone marrow generate daughter cells that go through stages of development within the marrow and eventually mature into cells that circulate in the blood: red blood cells (RBCs), white blood cells (WBCs), and platelets. These are the cells that perform their various important functions throughout the body:

• RBCs carry oxygen throughout the body
• WBCs fight infection
• Platelets protect against easy bleeding by helping your blood to clot

Blood Cell Formation in MDS

In MDS, blood stem cells don’t function normally. Instead of making healthy RBCs, WBCs or platelets, and releasing them into the blood stream, the stem cells mature abnormally. They tend to remain at an immature stage and to die prematurely, even before getting out of the marrow.  So most patients with MDS (80 to 85 percent) have more cells in their marrow than do healthy people (this is called hypercellular marrow), but the cells do not live to make it into the blood or they do not stay in circulation long. This is why patients with MDS have cytopenia, or low levels of one or more types of blood cells in their circulation.

• A low level of RBCs is called anemia. 
• A low level of WBCs is called neutropenia. 
• A low level of platelets is called thrombocytopenia.

Low levels of blood cells, or low blood cell counts, cause the symptoms of MDS.

MDS Progression
 

MDS progresses in one of two ways over time:

• In most patients, fewer and fewer healthy blood cells are produced or survive. This can lead to severe anemia (low RBCs), increased risk of infection (due to low WBCs), or risk of severe bleeding (due to low platelets).
• In about 30 percent of patients, the number of very immature abnormal cells in the marrow, called “blast cells” or “blasts,” increases, and MDS transforms into acute leukemia, [LINK TO leukemia page] a cancer of the marrow and blood. This is why MDS is also referred to as “preleukemia” or “smoldering leukemia.

Subtypes of MDS

Doctors divide MDS into subtypes depending on:

• Whether you have increased numbers of blast cells in your bone marrow (or  blood), and what percentage of your blood or marrow is made up of these blasts
• Whether the marrow shows dysplasia in only one type of blood cell (unilineage dysplasia) or in more than one type of blood cell (multilineage dysplasia)
• Whether there are chromosome abnormalities in the marrow cells and, if so, which type or types of abnormalities
• Doctors also look at the surface markers of MDS cells to see whether the cells express certain antigens. Antigens are substances (often proteins) that are recognized by the immune system.
• These and additional factors (in particular, other health problems) may help your doctor decide which treatment options 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). This subtype means that you have too few RBCs in your blood (you have anemia), and the marrow shows “dysplastic” cells only among those that make RBCs. Your RBC and platelet counts may be normal.
• Refractory anemia with ring sideroblasts (RARS). Ring sideroblasts are early stages of RBCs that have accumulated abnormal amounts of iron, which shows up as a ring when stained with a particular dye. This subtype typically means that you have too few RBCs in your blood (you have anemia). Your WBC and platelet counts may be normal.
• Refractory cytopenia with multilineage dysplasia (RCMD). This subtype means that your marrow shows “dysplastic” changes not only in the cells making RBCs but also in those making WBCs or platelets (or both). You usually have too few cells of at least one cell type in your blood. You also have a low percentage of blasts in your marrow and blood. If a person has multilineage dysplasia and ring sideroblasts, this is classified as RCMD-RS. 
• Refractory anemia with excess blasts 1 (RAEB1) and refractory anemia with excess blasts 2 (RAEB2). These subtypes mean that you have at least 5% or at least 10 percent but less than 20% blasts in your marrow. 
• MDS associated with isolated abnormality of chromosome 5 [del(5q)]. This subtype means that part of chromosome #5 is missing. You typically have too few RBCs in your blood (you have anemia). You have a low percentage of blasts in your marrow and blood.
• MDS unclassified (MDS-U). This subtype means that your marrow shows “dysplastic” cells among those that make WBC or platelets (but not among those that make RBCs) You have a normal percentage of blasts in your marrow and blood. And your MDS does not fit into one of the other subtypes.
• View details of the WHO classification system.

Symptoms
 

In the early stages of MDS, many patients have no symptoms. But a routine blood test may show reduced levels of red blood cells or possibly reduced white blood cells or platelets.

Some patients have symptoms related to their low blood cell counts. Symptoms can range from mild to severe and can vary greatly from patient to patient. Symptoms related to low RBCs (anemia) may include:

• Fatigue
• Shortness of breath
• Paler skin than usual
• Weakness
• Dizziness
• General malaise
• Rapid heart beat

Symptoms related to low WBCs (neutropenia) may include:

• Fever
• Frequent infections 
• Infections that won’t resolve

Symptoms related to low platelets (thrombocytopenia) may include:

• Easy bruising
• Unexplained bleeding

Of course, other conditions besides MDS can cause these symptoms. If you have these symptoms, it’s important to see a doctor to find the cause.
 

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 abnormal and, if so, which ones. Common blood tests include the following:

• Complete blood cell count (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 other factors

For a definitive diagnosis, doctors generally will need to perform a bone marrow aspiration and 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 marrow from the bone (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, doctors will perform cytogenic analysis. This means the marrow cells will be set up in a culture dish to make them divide. This will then allow us to see the chromosomes under a microscope and to identify the presence of abnormal chromosomes. 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 contain our genes and can 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.
 

Prognosis & Staging
 

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 under 5 percent, 5 to 9 percent, 10 to 19 [percent, or more than 20 percent)
• Which, if any, chromosome abnormalities are present 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 (Int-2), or high risk. This is basically the staging system for MDS. Keep in mind that risk groups provide only estimates for groups of patients; they cannot predict the precise outlook for you as an individual patient.

Risk Factors

It is currently not known what causes the cellular changes that lead to MDS. When MDS develops in patients who have some other disease that has been shown to lead to MDS or in patients who have been treated with chemotherapy or radiation for some other illness, MDS is referred to as secondary MDS or treatment-related MDS. If none of those conditions is present, doctors call it de novo MDS.

It’s not clear at this time what other factors may cause MDS. Exposure to toxins, such as benzene, certain solvents or pesticides, and heavy metals, such as mercury or lead may be involved. Some data suggest that smoking tobacco will increase the risk of MDS. It is extremely difficult, if not impossible, to establish a clear cause-and-effect relationship between those exposures and the development of MDS.

So far there has been no good epidemiologic study in the United States to better define factors that are important in the development of MDS. (Epidemiology is the study of how common a disease is, how the disease is distributed and how it might be controlled in a population.) Researchers at the SCCA and the Fred Hutchinson Cancer Research Center have recently initiated studies to compare people without MDS to patients with MDS in an effort to learn more about factors that may increase risk for the disease. We invite you to talk with your doctor about participating in these studies.

MDS is more common in men than in women. The incidence of MDS increases throughout adulthood, and it is most common after the age of 50 years. About 80 percent of people with MDS are over age 60. Advanced age sometimes complicates treatment of MDS because older people are more likely to have other health problems, too. Children can develop MDS; most who do develop MDS suffer from some other genetic disease.