Myelodysplastic syndrome (MDS) is a form of a precancerous blood condition. People develop MDS when their body starts making abnormal blood cells. In some cases, MDS can transform into acute myeloid leukemia (AML), a more aggressive form of blood cancer. However, most people with MDS will not develop leukemia.

How Does Myelodysplastic Syndrome Develop?

Blood cells are formed in the bone marrow, the spongy tissue found inside certain bones. They develop from immature cells called stem cells and progenitor cells, which then develop into specific types of blood cells. Normally, healthy blood cells eventually leave the bone marrow and circulate throughout the body in the blood. The blood cells have different roles:

• Red blood cells carry oxygen to all of the body’s cells.
• White blood cells fight infection.
• Platelets clot the blood after a blood vessel is injured.

Myelodysplastic syndrome derives part of its name from the word “dysplastic,” which refers to abnormal cell development or growth. In people with MDS, abnormal stem cells or progenitor cells produce blood cells that don’t function correctly. The defective blood cells can’t carry out their tasks properly and die quickly. Some of the defective cells never leave the bone marrow, crowding out the normal, healthy blood cells that are forming there.

Myelodysplastic Syndrome and Myeloproliferative Neoplasms

MDS is related to another group of conditions called myeloproliferative neoplasms (MPNs). Like MDS, MPNs are blood cell diseases that can progress to AML. In MPNs, the abnormal blood cells don’t respond to the body’s signal to limit growth. While people with MDS have low numbers of abnormal blood cells, people with MPNs have high levels of one or more types of blood cells.

Who Gets Myelodysplastic Syndrome?

Between 12,000 and 20,000 people are diagnosed with MDS each year in the U.S. Although MDS can affect people of all ages, about 75 percent of people who develop MDS are at least 60 years old.

People with the following risk factors are more likely to develop MDS:

• Being age 60 or older
• Being exposed to chemicals like pesticides, benzene, or tobacco smoke
• Being exposed to heavy metals like lead or mercury
• Undergoing cancer treatment, including chemotherapy or radiation therapy

MDS is called treatment-related or secondary MDS when it occurs in someone who has previously had cancer treatment or has been diagnosed with another blood disorder. When MDS occurs on its own, doctors call it primary MDS.

Types of Myelodysplastic Syndromes

MDS always leads to two different signs: dysplastic blood cells and low levels of one or more types of blood cells. However, the type of blood cell affected, the appearance of the abnormal blood cells, and gene changes within the cells may vary. Therefore, experts divide MDS into different subtypes.

The World Health Organization has developed a system to classify the types of MDS. When diagnosing a person’s subtype, doctors consider a few different factors, which include:

• The low levels of different types of blood cells
• Whether the cells have dysplasia
• How many cells are blasts (immature blood cells)

MDS With Single Lineage Dysplasia (MDS-SLD)

People with MDS-SLD have dysplasia in one type of blood cell and low levels of certain types of blood cells. MDS-SLD is not very aggressive, and people with this condition may not need treatment. Refractory cytopenia with unilineage dysplasia (RCUD) is a previously used name for MDS-SLD.

MDS With Multilineage Dysplasia (MDS-MLD)

People with MDS-MLD have abnormalities in two or more types of blood cells. They may also have low levels of one or more cell types. Doctors used to refer to MDS-MLD as refractory cytopenia with multilineage dysplasia (RCMD).

MDS With Ring Sideroblasts (MDS-RS)

People with MDS-RS have high levels of ring sideroblasts — immature red blood cells that have clusters of iron in the shape of a ring. MDS-RS may also be called refractory anemia with ring sideroblasts (RARS).

There are two subtypes of MDS-RS:

• MDS-RS-SLD — This refers to MSD-RS with single lineage dysplasia, meaning only one type of a person’s blood cells is abnormal.
• MDS-RS-MLD — This refers to MDS-RS with multilineage dysplasia, which occurs if more than one cell type is abnormal.

MDS With Excess Blasts (MDS-EB)

MDS-EB is characterized by high numbers of blasts. There are two subtypes of MDS-ED:

• MDS-EB1 — In this subtype, 5 percent to 9 percent of a person’s bone marrow cells are blasts, or 2 percent to 4 percent of their blood cells are blasts.
• MDS-EB2 — In this subtype, 10 percent to 19 percent of the bone marrow cells are blasts, or 5 percent to 19 percent of blood cells are blasts.

People with MDS-EB also have low levels of one or more types of blood cells. People with this condition have a higher risk of progressing to leukemia. MDS-EB was formerly called refractory anemia with excess blasts (RAEB).

MDS With Isolated del(5q)

People with this type of MDS have a chromosome change in their blood cells. Chromosomes are pieces of DNA that contain a cell’s genes. The “del(5q)” portion of the name means that part of chromosome 5 is gone. This chromosome change causes a type of MDS that results in dysplasia and low levels of certain types of blood cells.

MDS, Unclassifiable (MDS-U)

When a person has MDS but their disease signs don’t match up with any of the above categories, their doctor will likely diagnose them with MDS-U.

Symptoms of Myelodysplastic Syndrome

The symptoms a person with MDS experiences depend on which type of MDS they have and which blood cells are affected. For many people with MDS, anemia (low red blood cell count) is the first sign they experience. Anemia can cause:

• Tiredness
• Difficulty focusing
• Pale skin
• Loss of appetite
• Weight loss
• Breathing problems
• Fast heartbeat
• Trouble undergoing physical activity

Some people with MDS also develop neutropenia (low white blood cell count). Because white blood cells are responsible for fighting infection, many neutropenia symptoms are related to frequent infections. People who don’t have enough healthy white blood cells may experience:

• Fevers
• Sinus infections, which can cause headaches and a runny or stuffy nose
• Lung infections, which may cause coughing and breathing problems
• Bladder infections, which can cause pain or difficulty urinating
• Skin infections
• Mouth sores

People with MDS may also have thrombocytopenia (low platelet counts), which can lead to:

• Easy bruising
• Bleeding problems, including nose bleeds, bleeding gums, or bleeding more than usual after a small cut
• Heavy menstrual periods
• Petechiae (tiny red spots in your skin)

Treatments for Myelodysplastic Syndrome

Treatments for MDS can attack abnormal blood cells, lower levels of immature blast cells, and increase levels of healthy blood cells. When recommending your treatment plan, your doctor will likely weigh several different factors, including:

• How old you are
• What other health conditions you have
• What symptoms you have
• What type of MDS you have
• Whether you have factors that put you at high risk of developing AML or having a poor outlook
• Whether a matching bone-marrow donor can be found for a stem cell transplant

Watch and Wait

If you don’t have many MDS signs or symptoms and your condition is not advanced, you may not need treatment. A watch-and-wait approach means that you have regular follow-up visits so that your doctor can keep an eye on your condition, but you won’t take any medication to treat MDS. If your MDS gets worse, your doctor may recommend beginning treatment.

Supportive Care

Supportive care eases some of the symptoms of MDS. For example, people without enough healthy white blood cells can’t fight off germs as well as the general population. Doctors may prescribe antibiotics to prevent or treat infections.

Some supportive care treatments can raise levels of normal blood cells. During a blood transfusion, for example, blood cells from a healthy donor are delivered into the bloodstream. A transfusion may contain all of the different blood cells. Alternatively, a person with MDS may get a transfusion that contains only one component, such as red blood cells or platelets.

Other supportive care treatments, like growth factors, boost the ability of the body to make its own blood cells. Growth factors can increase levels of different blood cell types.

• Red blood cell growth factors include Epogen (epoetin) or Aranesp (darbepoetin alfa)
• White blood cell growth factors include Neupogen (filgrastim or granulocyte colony-stimulating factor), Neulasta (pegfilgrastim), or Leukine (sargramostim or granulocyte macrophage-colony stimulating factor)
• Platelet growth factors include Nplate (romiplostim), Promacta (eltrombopag), or Neumega (oprelvekin or interleukin-11)

Chemotherapy

Many people with MDS use chemotherapy medication such as:

• Dacogen (decitabine)
• Inqovi (decitabine and cedazuridine)
• Onureg (azacitidine)

These medications may help:

• Improve symptoms
• Boost quality of life
• Prevent MDS from turning into AML
• Increase how long a person with MDS lives

Unfortunately, many cases of MDS eventually become resistant to treatment. Another newer drug, SGI-110 (guadecitabine), is similar to decitabine and is currently being tested in clinical trials.

People who have high numbers of blast cells have high-risk MDS, which has a greater chance of progressing to AML. Chemotherapy drugs used to treat AML may help treat these cases of MDS.

Targeted Therapy

Targeted therapies block certain proteins or genes within cancer cells, largely leaving normal cells alone. One targeted therapy, Reblozyl (luspatercept-aamt), has been approved to treat anemia in people with MDS-RS. Luspatercept helps the body make more red blood cells.

Other targeted therapies currently being studied in MDS include:

• Estybon (rigosertib)
• Imetelstat
• Pevonedistat
• Selinexor
• Daurismo (glasdegib)

Immunosuppressants

Immunosuppressants are medications that reduce the activity of the immune system. These drugs may help certain people with MDS, because, in some cases, the immune system may be responsible for stopping the body from making healthy blood cells. Immunosuppressants used to treat MDS include Atgam (anti-thymocyte globulin or ATG) and Gengraf (cyclosporine).

Immunomodulating Drugs

Drugs that activate the immune system, including Revlimid (lenalidomide), can also help treat MDS. Lenalidomide may be recommended for people with MDS with isolated del(5q). Lenalidomide kills MDS cells and also spurs the immune system to attack cancer cells. It may help people get healthy enough to avoid blood transfusion, prevent MDS from turning into AML, and help people with MDS live longer.

Stem Cell Transplant

Some people with MDS may be able to get an allogeneic stem cell transplant. During this procedure, the recipient first undergoes high-dose chemotherapy, or radiation, to destroy the stem cells in their bone marrow. They then receive healthy new stem cells from a donor.

A stem cell transplant is the only treatment option that has the potential to cure MDS, making the abnormal bone marrow cells disappear for good. Stem cell transplantation can have serious side effects, however, and is often only an option for people who are younger and in good health. Graft-versus-host disease (GVHD) — a condition in which transplanted cells attack the host — can be a complication of a stem cell transplant. GVHD can be severe and requires treatment.

MDS Outlook

People with low-risk MDS live for an average of 5.3 years. Those diagnosed with high-risk disease live for an average of 1.6 years.

Doctors assess risk based on the International Prognostic Scoring System (IPSS). This system assigns a score for different factors that increase or decrease a person’s chances of having a worse prognosis (outlook). The IPSS is based on three factors:

• Gene changes — Changes linked to a poor prognosis are given a higher score.
• Cytopenia — Having low levels of more than one type of blood cell leads to a higher score.
• Amount of blasts in the blood or bone marrow — A higher blast count leads to a higher score.

The higher the IPSS score, the higher-risk MDS you have. If you have high-risk MDS, you may be more likely to be diagnosed with leukemia and have a poor prognosis. If you are interested in learning more about your own prognosis, ask your doctor about how your own risk factors may affect your outcome.

When Does MDS Progress to Leukemia?

Across all people with MDS, about 3 out of 10 will develop acute myeloid leukemia. However, each person’s risk of AML is not the same. Risk is partly based on which MDS subtype a person has. For example, MDS-SLD and MDS-RS have a 10 percent to 20 percent chance of progressing to AML, but people with MDS-EB have a 40 percent chance of developing leukemia.

A person’s IPSS score can also indicate whether their MDS will progress to leukemia. People with a low IPSS score have a lower chance of developing leukemia than people with a high IPSS score do.

Talk With Others Who Understand

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