Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes (MDS) are a group of diseases that affect the bone marrow and blood. Some types of MDS are mild and easily managed, while other types are severe and life-threatening. Mild MDS can grow more severe over time. It can also develop into a fast-growing, severe leukemia called acute myelogenous leukemia.
MDS causes, symptoms and diagnosis About 10,000 to 15,000 people are diagnosed with myelodysplastic syndromes in the United States each year. Although MDS can affect people of any age, more than 80% of cases are in people over age 60. MDS is more common in men than in women.
Causes of MDS In MDS, the bone marrow does not make enough normal blood cells for the body. One, two or all three types of blood cells — red blood cells, white blood cells and platelets — may be affected. The marrow may also make unformed cells called blasts. Blasts normally develop into red blood cells, white blood cells or platelets. In MDS, the blasts are abnormal and do not develop or function normally.
Most often the cause of the changes to the bone marrow is unknown. This is called de novo MDS. In a small number of people, MDS might be linked to heavy exposure to some chemicals, such as certain solvents or pesticides, or to radiation. MDS can also be caused by treatment with chemotherapy or radiation therapy for other diseases. This is called treatment-related MDS or secondary MDS. Treatment-related MDS is often more severe and difficult to treat than de novo MDS.
MDS symptoms The symptoms of MDS depend on how severe the disease is. Many people with MDS have no symptoms when they are diagnosed. Their disease is found through a routine blood test. If a person does have symptoms, they are caused by low numbers of blood cells:
- Red blood cells carry oxygen throughout the body. Low numbers can lead to anemia — feeling tired or weak, being short of breath and looking pale. Anemia is the most common symptom of MDS.
- White blood cells fight infection. Low numbers can lead to fever and frequent infections.
- Platelets control bleeding. Low numbers can lead to easy bleeding or bruising.
In severe MDS, infection or uncontrolled bleeding can be life-threatening.
Diagnosis MDS is one of several diseases with these symptoms. Doctors look at samples of blood and bone marrow to diagnose MDS. They also look for changes in the chromosomes of bone marrow cells (cytogenetics).
MDS can be hard to diagnose. Careful study of blood and marrow samples is needed to tell MDS apart from other diseases with similar signs and symptoms, such as aplastic anemia. Blood and marrow samples are often tested several times over two or more months to find out whether the disease is stable or getting worse.
MDS is a group of diseases that have many differences. It is important to diagnose the type of MDS to make the best treatment choices. With some types of MDS, a person may live with few symptoms for years, while other types can be life-threatening within months. In addition, some types of MDS are more likely than others to develop into acute myelogenous leukemia (AML). AML that develops from MDS can be hard to treat.
MDS types and risk scores
Types of MDS The likely course of MDS can be very different for different people. Experience has shown that certain disease factors affect a person's prognosis — his or her chances of long-term survival and risk of developing AML. Researchers use these factors to classify MDS into types.
The system that has been used for decades to classify MDS is called the FAB system because it was developed by a team of French, American and British researchers. In the FAB system, there are five types of MDS.
The FAB system uses several disease factors to classify MDS. One important factor is the percent of blasts in the bone marrow (Table 1). A higher percent of blasts is linked to a higher likelihood of developing AML and a poorer prognosis.
The two more common types of MDS are refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS). These are also the less severe forms of MDS. They have a lower risk of turning into AML. Some patients with these forms of MDS may live with few symptoms and need little treatment for many years.
The other types of MDS tend to be more severe and more difficult to treat successfully. The refractory anemia with excess blasts (RAEB) and refractory anemia with excess blasts in transformation (RAEB-t) forms of MDS also have a high risk of turning into AML.
Table 1. MDS Types in the FAB System
| Type of MDS |
Percent of blasts in marrow (less than 5% is normal) |
| Refractory anemia (RA) |
Less than 5% (normal amount) |
| Refractory anemia with ringed sideroblasts (RARS) |
Less than 5% (normal amount), plus more than 15% of abnormal red blood cells called ringed sideroblasts |
| Refractory anemia with excess blasts (RAEB) |
5% to 20% |
| Refractory anemia with excess blasts in transformation (RAEB-t) |
21% to 30% |
| Chronic myelomonocytic leukemia (CMML) |
5% to 20%, plus a large number of a type of white blood cell called monocytes |
Although the type of MDS can help predict the course of a person's disease, people with the same type of MDS may respond to the disease and to treatment differently.
To try to better predict people's outcomes, researchers developed another system for defining types of MDS. The newer World Health Organization (WHO) system divides MDS into eight types. Today a doctor may use either the FAB or WHO system to determine the type of MDS a person has. Either system can be helpful in planning a patient's treatment.
MDS risk scores Researchers have developed one other system for classifying MDS. This system is called the international prognostic scoring system (IPSS). The IPSS risk score describes the risk that a person's disease will develop into AML or become life-threatening.
A doctor may use the IPSS risk score along with the MDS type to plan treatment. The IPSS risk score is based on three factors that have been shown to affect a patient's prognosis:
- The percent of cells in the bone marrow that are blasts.
- Whether one, two or all three types of blood cells are low (also called cytopenias). The three types are red blood cells, white blood cells and platelets.
- Changes in the chromosomes of bone marrow blood cells. This may be called cytogenetics (the study of chromosome abnormalities). It may also be called the karyotype (a picture of the chromosomes that shows whether they are abnormal).
A person may have an IPSS risk score of low, intermediate-1, intermediate-2 or high risk. Doctors can use the risk score to plan treatment. Someone with low-risk disease may be likely to survive for years with few symptoms. That person may need less intense treatment. Someone with intermediate-1, intermediate-2 or high-risk disease may be likely to survive only if he or she receives aggressive treatment, such as a transplant.
However, people with the same risk score and type of MDS can still respond differently to treatment. A person's age, overall health and other factors all influence his or her response to the disease and treatment. A doctor will also look at all these factors when planning treatment. If you have MDS, it is important to talk with your doctor about what type of MDS you have and your risk score. Ask how this information affects your treatment options.
Treatment options The best treatment for a person with MDS depends on his or her type of MDS, risk level, age, overall health and his or her own preferences. The treatment options (all discussed further below) include:
- Supportive care
- Bone marrow or cord blood transplant (BMT)
- Chemotherapy
- Newer drug therapies
Whichever treatment you and your doctor decide on, you may choose to be part of a clinical trial. Even standard treatments continue to be studied in clinical trials. These studies help doctors improve treatments so that more patients can have better results.
Supportive care Supportive care will be part of the treatment plan for all people with MDS. The goal of supportive care is to manage disease symptoms and related problems.
For some people, supportive care may be the only treatment needed. Some people with few symptoms may need only regular doctor visits. The doctor will watch for any signs the disease is getting more severe.
Some people with more severe MDS may also choose supportive care as their only treatment. People who are older or who have other health problems may be unable to tolerate stronger treatment. Other people weigh the possible risks and benefits of different treatment options and choose supportive care. Supportive care does not offer the possibility of a long-term remission from MDS, but it may offer a way to manage a person's symptoms.
Blood transfusionsMany people with MDS need blood transfusions to manage symptoms caused by low numbers of red blood cells and/or platelets.
- Red blood cell transfusions reduce problems with being very tired and short of breath.
- Platelet transfusions reduce risks of bleeding problems caused by very low numbers of platelets.
If you have MDS, your doctor will determine when you need transfusions and manage the possible risks. To manage transfusion risks, your doctor may:
- Give you additional treatment to remove iron from the body (iron chelation therapy). After many red blood cell transfusions, iron builds up in the body, causing organ damage.
- Give as few platelet transfusions as possible to limit the risk of the immune system developing antibodies (immune cells) that attack transfused platelets. If this happens, platelet transfusions must be closely matched to the patient.
- Treat blood cells with radiation and filter out white blood cells before transfusion. This reduces the risks of an immune system reaction against transfused platelets.
Growth factors
Growth factors are drugs that help the body make more blood cells. A person with MDS may be given growth factors to try to reduce the need for red blood cell transfusions. However, in many cases of MDS, the marrow does not respond to growth factors.
Growth factors may also be given after a transplant. In this case, growth factors often are effective. They can help speed up new blood cell production, reducing a person's need for transfusions and risk of infection.
Bone marrow or cord blood transplant for MDS The only known treatment that can bring a long-term remission from MDS is a bone marrow or cord blood transplant (also called a BMT). A transplant replaces the abnormal cells in the bone marrow with healthy blood-forming cells from a family member or unrelated donor or cord blood unit.
The standard transplant for MDS is allogeneic, which uses blood-forming cells from a family member, an unrelated donor or a cord blood unit. The donor for a transplant must closely match the patient's tissue type. The best donor is usually a matched sibling. For patients who do not have a suitable donor in their family, doctors may search the National Marrow Donor Program (NMDP) Registry for a matching adult volunteer donor or cord blood unit.
A transplant can offer some people the chance for a long-term remission of disease and a longer life, but it is not an option for all patients. A transplant may be a good option for people who have a suitable donor or cord blood unit and are healthy enough to tolerate a transplant. In general, younger patients tend to do better after a transplant than older patients. However, advances in transplant have enabled more older patients to undergo a transplant successfully.
Reduced-intensity transplant for MDS Before a transplant, a patient receives a preparative regimen of high-dose chemotherapy with or without radiation therapy. Many patients with MDS are older and have other health problems that may make them unable to tolerate this high-dose regimen. However, some may be able to tolerate a reduced-intensity regimen, which uses lower doses of chemotherapy and low-dose or no radiation therapy.
Reduced-intensity transplant is a newer approach to transplant for MDS, and early results have been encouraging. The use of reduced-intensity transplant to treat MDS is growing. This approach may offer the chance for long-term survival to some patients, especially those who are older or have other health problems.
Autologous transplant for MDS The standard transplant for MDS is allogeneic, which uses blood-forming cells from a family member, an unrelated donor or a cord blood unit. Another type of transplant is an autologous transplant, which uses the patient's own blood-forming cells. An autologous transplant is a standard treatment for some diseases and is being studied in clinical trials as a treatment for MDS. An autologous transplant may be an option for patients who do not have a suitable donor for an allogeneic transplant.
In an autologous transplant, blood-forming cells are collected from the patient. After treatment with high-dose chemotherapy and possibly radiation therapy, the patient receives his or her own cells back.
Autologous transplants have risks of serious side effects, but these risks are lower than for allogeneic transplants. However, a patient has higher risks of a relapse of MDS after an autologous transplant. This may be because disease cells may be returned to the patient along with his or her blood-forming cells.
Transplant success rates Transplants have risks of serious complications, but a transplant offers some patients the best chance for a long-term remission. If transplant is an option for you, talk with your about the possible risks and benefits of a transplant. For statistics showing patients' results after transplant, see MDS Transplant Outcomes.
Induction chemotherapy Chemotherapy uses drugs to destroy abnormal cells or stop them from growing. A treatment option for some people with severe MDS may be induction chemotherapy. Induction chemotherapy is very intense. The goal is to bring the disease into remission (no more signs of disease).
Induction chemotherapy may be an option for patients with high IPSS risk scores who are in good overall health but do not have a suitable donor for a transplant. Induction chemotherapy is also sometimes used to bring MDS into remission before a patient receives a transplant.
About half of patients treated with induction chemotherapy may reach a remission, but relapse is common and the rate of long-term survival is low, particularly in older patients. Because of the high relapse rate, patients may be given further treatment, such as a transplant or more chemotherapy.
In addition, many people with MDS, especially those who are older or who have other health problems, may be unable to tolerate intensive induction chemotherapy. Different chemotherapy regimens for MDS, some low-intensity and some high-intensity, are being studied in clinical trials to try to find a more effective approach.
Newer drug therapies Much research is being done to find better treatment options for patients with MDS. Many newer drug therapies have been shown to bring a response in some patients with MDS. These therapies have either been approved by the U.S. Food and Drug Administration (FDA) or continue to be studied in clinical trials.
For some drug therapies, the goal is a long-term remission of the disease and long-term survival. For many other drug therapies, the goal is to improve a person's blood counts and symptoms. Managing the symptoms and related problems of MDS may offer a higher quality of life and a somewhat longer life than supportive care alone.
If you have MDS, talk with your doctor about the many newer drug therapies available. Your doctor can help you determine which, if any, are good options for you. Your doctor can also help you find clinical trials offering these treatments, if they are appropriate for you.
Making treatment choices If you are diagnosed with MDS, it is important to talk with a doctor who has experience treating MDS. Ask about the type of MDS you have, your risk factors and treatment options, and discuss your own treatment goals. There are a variety of treatment options available, including newer treatments being studied in clinical trials. The best treatment for you will depend on your type of MDS, risk score, age, overall health and your own preferences.
Planning for possible transplant If a transplant may be a treatment option for you, your doctor will refer you to a transplant doctor for a consultation. A transplant doctor can determine whether a transplant is a good treatment option for you.
The NMDP and American Society of Blood and Marrow Transplantation (ASBMT) recommend a patient be referred to a transplant doctor for consultation based on IPSS risk scores. Referral is recommended for patients with an intermediate-1, intermediate-2 or high risk score who have one or more of the following factors:
- More than 5% blasts in the bone marrow
- Intermediate or high-risk cytogenetic factors
- Low blood counts for more than one type of blood cell (red blood cells, white blood cells and platelets)
A transplant doctor can also help determine the best time for a transplant. An early consultation with a transplant doctor enables your doctors to plan ahead even if a transplant is not your first treatment choice. The transplant doctor can begin the search for a suitable donor among family members and the National Marrow Donor Program Registry of unrelated donor and cord blood units. Taking the first steps of the donor search early may enable a quicker transplant if you need one.
Information to share with your doctor The Physician Resources section of this Web site includes information for doctors about timing and outcomes of transplants for MDS, as well as references to related medical journal articles. You may want to share some of this information with your doctor.
More information on MDS
You can get further information about MDS from disease-specific organizations, such as:
For other organizations that offer information and resources, see Organizations That Can Help: A Searchable Directory.
Contributing editorsC. F. LeMaistre, M.D., Southwest Texas Methodist Hospital, San Antonio, Texas
Anthony S. Stein, M.D., City of Hope National Medical Center, Duarte, Calif.
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