Myelodysplastic syndrome (MDS) involves abnormal production of blood cells in your bone marrow.
- What is MDS?
- How does MDS progress?
- Prognosis and staging
- What causes MDS?
- How common is MDS?
- Next steps
What is MDS?
MDS is not a single disease but a group of diseases that affect blood-cell formation. In all subtypes of MDS, a chronic bone marrow problem leads to low levels of blood cells circulating in your bloodstream.
- “Myelo” refers to bone marrow, which is the body’s blood-cell factory.
- “Dysplastic” refers to abnormal growth or development.
- “Myelodysplastic” means the bone marrow produces abnormal blood cells.
To understand more about MDS, it’s helpful to understand the basics of how blood cells normally form.
Healthy blood-cell formation
In a healthy person:
- Stem cells in your bone marrow make daughter cells.
- Daughter cells go through several stages of development within your marrow.
- Eventually, they mature into red blood cells (RBCs), white blood cells (WBCs) or platelets.
- The mature cells get released from your marrow to circulate in your bloodstream.
The circulating cells perform important functions.
- RBCs carry oxygen throughout your body.
- WBCs fight infection.
- Platelets protect against easy bleeding by helping your blood to clot.
Blood-cell formation in MDS
In a person with MDS:
- Stem cells in your bone marrow don’t function normally.
- Instead of producing healthy, mature RBCs, WBCs and platelets, your marrow makes cells that tend to remain immature and to die early.
About 80 to 85 percent of people with MDS have more cells in their marrow than healthy people do (hypercellular marrow). But these cells do not live long enough to make it out of the marrow into the bloodstream, or they are not in circulation long before they die.
As a result, people with MDS have low levels of one or more types of blood cells in their bloodstream (cytopenia).
- A low level of RBCs is called anemia.
- A low level of WBCs is called leukopenia.
- A low level of platelets is called thrombocytopenia.
Low levels of blood cells, or low blood counts, cause the symptoms of MDS.
How does MDS progress?
MDS progresses over time in two ways.
- In most people with MDS, 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 people with MDS, the number of very immature abnormal cells in the marrow (blast cells, or blasts) increases, and MDS transforms into acute leukemia. This is why MDS is also called preleukemia or smoldering leukemia.
Subtypes of MDS
Doctors divide MDS into subtypes based on:
- Whether you have increased numbers of blast cells in your bone marrow or blood and what percentage of your marrow or blood is made up of blasts
- Whether your marrow shows abnormal growth in only one type of blood cell (unilineage dysplasia) or in more than one type of blood cell (multilineage dysplasia)
- Whether your marrow cells have chromosome abnormalities and, if so, which type or types
Doctors also look at the surface markers of MDS cells to see whether the cells express certain antigens. Antigens are substances that the immune system recognizes. Researchers at Fred Hutchinson Cancer Research Center pioneered the process of detecting MDS cells by flow cytometry and developing models based on surface markers to help diagnose the disease and predict the outcome.
These and other factors, such as any other health problems you have, 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 system of MDS classification.
- MDS with single-lineage dysplasia (MDS-SLD) — You have too few RBCs, WBCs or platelets in your blood. (Occasionally patients are low in two types of blood cells.) Your marrow shows dysplastic changes in only one of the three types of blood cells. You have a low percentage of blasts in your marrow and blood. Depending on your blood counts, your condition may be called refractory anemia, refractory neutropenia or refractory thrombocytopenia.
- MDS with ring sideroblasts (MDS-RS) — Ring sideroblasts are early stages of RBCs carrying abnormal amounts of iron. The iron shows up as a ring when stained with a particular dye. This subtype typically means you have too few RBCs in your blood. Your WBC and platelet counts may be normal. You have a low percentage of blasts in your marrow and blood.
- MDS with multilineage dysplasia (MDS-MLD) — Your marrow shows dysplastic changes in the cells that make at least two types of blood cells. You also have a low percentage of blasts in your marrow and blood.
- MDS with excess blasts-1 (MDS-EB1) and MDS with excess blasts-2 (MDS-EB2) — You have at least 5 percent (EB1) or at least 10 percent (EB2) but less than 20 percent blasts in your marrow.
- MDS with isolated deletion 5q — Part of chromosome 5 is missing. Typically this means you have too few RBCs in your blood. You have a low percentage of blasts in your marrow and blood.
- MDS, unclassifiable (MDS-U) — Your marrow shows dysplastic changes in cells that make WBCs or platelets (but not in 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.
Some problems with blood-cell formation are not only myelodysplastic (having to do with abnormal production of cells in the marrow) or only myeloproliferative (having to do with overproduction of cells in the marrow). Instead, these problems have features of both MDS and myeloproliferative neoplasms. They include:
- Chronic myelomonocytic leukemia (CMML) — The main feature of CMML is that you have too many myelocytes and monocytes (types of WBCs) in your blood. You may have low levels of RBCs and platelets in your blood, and you may have abnormal cells in your marrow.
- Juvenile myelomonocytic leukemia (JMML) — JMML is similar to CMML, but it occurs in young children. It causes high levels of myelocytes and monocytes. The child may have low levels of RBCs and platelets in their blood and abnormal cells in their marrow.
- Atypical chronic myeloid leukemia (aCML), BCR-ABL 1–negative — You have too many granulocytes (a type of WBC). You may have low levels of RBCs and platelets in your blood, and you may have abnormal cells in your marrow. aCML is much like chronic myeloid leukemia (CML), except people with CML have a chromosome change called the Philadelphia chromosome; people with aCML do not have this change.
- MDS/MPN, unclassifiable — Your disease has features of MDS and MPN and does not fit into one of the other subtypes. This subtype includes refractory anemia with ring sideroblasts and thrombocytosis (RARS-T), which is like RARS (described above) but with the added feature that you have too many platelets in your blood.
Symptoms of MDS
In the early stages of MDS, many people have no symptoms. But a routine blood test may show low levels of RBCs, WBCs or platelets.
Some people have symptoms related to their low blood counts. These can range from mild to severe and can vary greatly from one person to another.
Other conditions besides MDS can cause the same symptoms. If you have these symptoms, see your doctor to find the cause.
Symptoms related to low RBCs may include:
- Shortness of breath
- Paler skin than usual
- General malaise
- Rapid heart beat
Symptoms related to low WBCs may include:
- Frequent infections
- Infections that won’t get better
Symptoms related to low platelets may include:
- Easy bruising
- Unexplained bleeding
To find out whether you have MDS, your doctor will do a thorough physical exam and ask about your health history and any symptoms. You will also have:
- Blood tests — to check how many cells of each type are in your blood (complete blood count), how the cells look (peripheral blood smear) and whether they have certain abnormalities (blood chemistry).
- Bone marrow aspiration and biopsy — using a needle to take small samples of your marrow. A pathologist examines the samples under a microscope to look for and count abnormal cells. This provides a definitive diagnosis.
- Cytogenetic analysis — tests of your marrow to look for chromosome abnormalities that help predict how your disease will progress and which types of treatment might be most effective.
Prognosis and staging MDS
For cancer, doctors typically use a system called staging to determine how early or advanced a person’s disease is (stage I for early cancer to stage IV for advanced cancer).
MDS has a different type of staging system. Doctors classify the disease using the Revised International Prognostic Scoring System (IPSS-R). Your IPSS-R score helps your doctor determine how fast your disease is likely to progress (your prognosis).
Your score is based on:
- The percentage of blasts in your bone marrow (less than 5 percent, 5 to 10 percent, 11 to 20 percent, or 21 to 30 percent)
- Which, if any, chromosome abnormalities are present in your marrow cells (categorized as good, intermediate or poor)
- The severity of your cytopenias (low blood counts, meaning low RBCs, WBCs and platelets)
Your score tells your doctor which risk group you are in: very low, low, intermediate, high or very high.
These risk groups are only estimates for groups of people. Your risk group is meant to give you and your doctor an idea of what might happen for you based on what usually happens for people whose MDS is similar to yours. Your score doesn’t predict the exact outlook for you as an individual.
What causes MDS?
Doctors don’t know what causes the cellular changes that lead to MDS.
Sometimes MDS develops in people who have been treated with chemotherapy or radiation for another illness or who have been heavily exposed to certain chemicals. In these cases, MDS is called secondary MDS or treatment-related MDS. Otherwise, doctors call it primary MDS or de novo MDS.
It’s not clear what other factors might 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 increases the risk. It is extremely difficult, if not impossible, to establish a clear cause-and-effect relationship between these exposures and the disease.
Researchers at SCCA and Fred Hutch have conducted studies to compare people without MDS to people with MDS to learn more about factors that may increase risk. We invite you to talk with your doctor about whether you can participate in studies like these.
The SCCA Hematologic Malignancy Genetics Clinic offers personalized risk assessment and follow-up care for adult patients and family members who may be at increased risk for developing blood-based malignancies due to an underlying genetic cause. Risk factors include being diagnosed with MDS before age 45 or having a known familial marrow failure syndrome or an inherited predisposition to hematologic malignancy, such as familial MDS.
How common is MDS?
Each year about 10,000 to 15,000 people are diagnosed with MDS in the United States. It is more common in men than in women.
The incidence of MDS increases throughout adulthood, and it is most common after age 50. About 80 percent of people with MDS are over 60.