What Are Myelodysplastic Syndromes and How Are They Treated?

Medically reviewed by David P. Steensma, MD

Myelodysplastic syndromes (MDS) are a group of diseases of the blood and marrow that result in the body being unable to produce enough healthy, mature blood cells.

MDS develops when the blood stem cells found in the bone marrow become injured (i.e., they acquire a mutation in the DNA that determines their function) and do not mature into healthy white blood cells, red blood cells, and platelets. Normally, white blood cells work to fight infection, red blood cells carry oxygen, and platelets help blood clot to stop bleeding. In MDS, cells may be reduced in number or may not work the way they should. As a result, there are fewer healthy red blood cells, white blood cells, and platelets.

In addition, a type of immature bone marrow cell called a blast cell can increase in MDS. Fewer than 5% of the marrow cells are blast cells in healthy persons. In some patients with MDS, the blasts increase to 5% or greater. If 20% or more blast cells are present in the marrow, the diagnosis is acute leukemia rather than MDS.

Who is at risk?

Myelodysplastic syndromes occur mostly in older patients; 75% of patients are more than 65 years old. The disease is very rare in children. Risk factors for MDS include:

  • Older age
  • Sex (slightly more common in men)
  • Previous cancer treatment with chemotherapy or radiotherapy
  • Certain rare inherited or inborn genetic syndromes such as Fanconi anemia, Down syndrome, or dyskeratosis congenita
  • Familial MDS (this accounts for less than 1% of MDS; relatives of patients with MDS usually do not have an increased risk of MDS)
  • Smoking
  • Environmental exposures such as high-dose radiation exposure and long-term exposure to benzene (benzene exposure is rare today).

What are the types of MDS?

There are two major categories of myelodysplastic syndromes. The first is primary or “de novo” MDS, where an external factor triggering the disease cannot be identified. In contrast, secondary or “therapy-related” MDS is developed after use of chemotherapy or radiation for cancer.  The term secondary MDS is also used to describe MDS resulting in children with inborn genetic syndromes.

In about one-third of patients, MDS progresses to a condition known as acute myelogenous leukemia (AML). Secondary or therapy-related MDS, from chemotherapy or radiation, has a higher risk for evolving to AML than primary MDS.

What are the symptoms of MDS?

The most common presenting symptom of MDS is fatigue and decreased ability to exercise or to carry on the usual daily activities. Anemia (low red cell count) is present in most patients with MDS; anemia can cause symptoms such as shortness of breath, swelling of the ankles, paleness or other signs and symptoms.

Less common presenting symptoms include bleeding (e.g. nose bleeds or gum bleeding) or easy bruising, due to low platelet counts or platelets that do not work well. Occasionally, patients with low white cells will first be diagnosed after they develop a serious infection  MDS is often discovered accidentally during routine blood tests.

How are MDS treated?

At Dana-Farber/Brigham and Women’s Cancer Center, adults with MDS are treated in the Hematologic Oncology Treatment Center. For these patients, there are several treatment options.

The only potentially curative approach for MDS is a bone marrow or stem cell transplant, also known as an allogeneic hematopoietic cell transplant, to destroy abnormal cells in bone marrow with chemotherapy or radiotherapy (“conditioning”) and replace them with healthy cells from a donor.

This approach has many potential serious side effects, including infections or a form of rejection called graft-versus-host disease. Older patients, such as those in their 60s or 70s, are often given a lower dose of radiation or chemotherapy prior to transplant, also known as reduced-intensity conditioning. This therapy may not destroy all bone marrow cells but is enough to allow donor cells to grow in the bone marrow.

Chemotherapy is useful for treating patients with MDS because it treats the entire body, killing abnormal cells and allowing normal ones to grow. A class of low-intensity chemotherapy drugs called hypomethylating agents kill cells that divide rapidly and activate some genes that help cells mature. Using one of these drugs can improve blood counts (sometimes eliminating the need for blood transfusions), lower the number of abnormal cells such as blasts, and lower the chances of getting leukemia.

Side effects include an initial a decrease in blood cell counts, which often later improves as the drug begins to take effect, as well as fever, skin rash, nausea/vomiting, and fatigue.  Examples of hypomethylating agents include azacitidine and decitabine.

For patients who have an abnormality of chromosome 5 in their bone marrow cells and have anemia and do not have increased blasts, a pill called lenalidomide may be helpful for improving blood counts.  Lenalidomide can cause blood clots or worsen low white blood count and platelets, and it doesn’t work as well for patients without a chromosome 5 abnormality.

In rare cases, intensive chemotherapy similar to that given to patients with acute leukemia may be necessary.  In certain cases, immune suppressing therapy with anti-thymocyte globulin, cyclosporin, tacrolimus or other drugs may be used.

Supportive therapy involves treating or preventing the symptoms of MDS, rather than treating the MDS directly by trying to eliminate abnormal cells. Supportive therapy can be used alone or with other treatments.

One supportive therapy option is hematopoietic growth factors. Hematopoietic growth factors are hormone-like substances that occur naturally in the body but can be produced synthetically and given in large doses than the body can make. These growth factors are typically injected subcutaneously (under the skin) to help bone marrow make new blood cells.  Erythropoietin (epoetin or darbepoetin) is a growth factor that increases red cells.  Less commonly, growth factors filgrastim or pegfilgrastim are used to increase white cells, or growth factors romiplostim or eltrombopag are used to increase platelets. Luspatercept is a new drug that improves red cell growth in certain MDS subtypes.

For patients who have had many red cell transfusions and have an excess of body iron, iron chelation medications such as deferasirox or deferoxamine may be used to lower iron levels and prevent injury to body organs.

Transfusions with red cells or platelets as needed and antibiotics to prevent or treat infections are other examples of supportive care used for MDS.

At Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, children with MDS are treated through the Bone Marrow Failure and Myelodysplastic Syndrome Program. Treatment is similar to adults, including supportive care, except that hematopoietic cell transplant is used more commonly in children.