The myelodysplastic syndromes (MDS, myelodysplasia) are a group of blood disorders associated with low blood counts. Normally, blood cells are produced by the bone marrow (the spongy area in the middle of bones) in a controlled fashion. In MDS, the bone marrow does not function effectively to produce one or more types of blood cells, including red blood cells, white blood cells, and platelets.
Each type of blood cell performs a number of functions, including the following:
- Red blood cells carry oxygen throughout the body
- White blood cells help to protect the body from infection
- Platelets helps blood to clot normally
In people with MDS, the bone marrow is unable to produce enough cells to keep up with the number of cells removed by the spleen, liver, and other organs. This leads to a reduced number of cells in the body, increasing the risk of bleeding, infection, and problems related to anemia. Anemia occurs when there is a reduced number of red blood cells, which can cause fatigue, shortness of breath, or heart failure.
MDS may occur on its own (called de novo MDS) or 1 to 15 years after being exposed to certain forms of chemotherapy or radiation (called treatment-related MDS). Most people (approximately 75 percent) are older than 60 years when they are diagnosed with MDS, although it can develop during childhood.
Some people with MDS have no symptoms, and are diagnosed after laboratory testing is done for another reason. Most people with MDS seek care due to symptoms of anemia, including fatigue, weakness, becoming tired quickly during activities, chest pain, dizziness, difficulty thinking clearly, or shortness of breath.
Less commonly, a person with MDS is diagnosed as a result of an infection, easy bruising, or bleeding. Symptoms such as fever and weight loss are uncommon early in the disease.
MDS is primarily diagnosed based upon laboratory testing, which includes the following:
- A complete blood count indicates the number of red and white blood cells, and platelets
- A blood smear involves examining a small sample of blood under a microscope to examine the number, size, shape, and type of blood cells
- Cytogenetic analysis examines the blood or bone marrow cells for signs of genetic abnormalities in the chromosomes. Researchers have discovered that the genetic makeup of the cells can vary, which can affect how a particular patient responds to treatment. Interpretation of these studies is very complicated. In general, outcomes are better for patients with normal chromosomes and worse for patients with complex changes in their chromosomes. However, certain chromosomal changes are associated with even better outcomes that those seen with normal chromosomes. Examples of these good changes include loss of the Y chromosome or deletion of the long arm of chromosomes 5 or 20.
- Bone marrow aspiration and biopsy is performed to remove a sample of bone marrow from inside of a bone (usually the hip bone) and examine it with a microscope to look for abnormal cells.
TYPES OF MYELODYSPLASTIC SYNDROME
Patients with MDS have been classified into subgroups, based in large part upon the blood counts, the number of abnormal cells in the bone marrow, and the cytogenetic studies. This classification system is called the World Health Organization classification and criteria for the myelodysplastic syndromes. A person's subgroup may change over time, as the disease progresses.
Perhaps the most useful clinical classification systems for MDS are the original and revised International Prognostic Scoring Systems (IPSS and IPSS-R, respectively). These models were devised to consider variables such as the percentage of immature blood cells (blasts) in the bone marrow, the type of blood abnormality present, as well as studies of the genetic makeup of the abnormal cells. Based on these criteria, the original IPSS defines four risk groups: low, intermediate-1, intermediate-2, and high-risk groups (table 1). Similar information is used by the IPSS-R to define five risk groups: very low, low, intermediate, high, and very high risk groups (table 2).
Treatment recommendations are based upon the patient's original or revised IPSS risk group; a person with low risk type MDS may live for many years before needing treatment while a person with high-risk type MDS usually needs more immediate treatment, without which his/her life expectancy may not exceed one to two years.
Other than blood or bone marrow transplantation, there is currently no cure for MDS, although a number of treatment options are available to control symptoms, prevent complications of MDS, and improve quality of life. Not all patients with MDS require immediate treatment. Immediate treatment is indicated for patients with symptoms related to MDS. Patients without symptoms are usually monitored closely for disease progression.
For patients with symptoms, our treatment approach is similar to that proposed by the National Comprehensive Cancer Network (NCCN). We choose a treatment based upon the patient's age, performance status (a measure of how well a patient can perform normal daily tasks), and disease characteristics such as the IPSS risk score.
Treatment options — Treatment options for patients with MDS typically fall into one of three categories:
- Supportive care includes the use of antibiotics for infection and transfusions for low blood counts. Supportive care is an important part of the management of all patients with MDS.
- High intensity treatment is more likely to be associated with “treatment-related mortality”, may require hospitalization, and includes combination chemotherapy with or without bone marrow transplantation. The trade-off for the higher risk associated with these therapies is a greater chance of effectiveness.
- Low intensity treatment includes those treatments less likely to produce treatment-related mortality and those that do not require a person to remain in the hospital, and includes use of hematopoietic growth factors, low intensity chemotherapy, immunosuppressive treatments, or a thalidomide derivative.
Treatment recommendations — Our general approach to the treatment of MDS is as follows:
- Patients with higher risk MDS (IPSS score greater than 1.5 or IPSS-R score greater than 4.5) who are young and otherwise healthy are generally treated with high intensity therapies (see 'High intensity treatments' below).
- Patients with lower risk MDS (IPSS score less than 1.5 or IPSS-R score less than 3) are generally treated with low intensity therapy or supportive care alone (see 'Low intensity treatments' below).
- Patients with intermediate risk MDS (IPSS-R score between 3 and 4.5) can be treated with either approach.
- Supportive care is an important adjunct to the management of all patients with MDS.
LOW INTENSITY TREATMENTS
Supportive treatments — Supportive care includes treatment for the signs or symptoms of MDS, including a low white blood cell, platelet, or red blood cell count. Due to the advanced age of most patients with MDS and the chronic nature of the disease, supportive care is an important part of treatment for all patients. These treatments are not intended to cure the disease, although they can improve a person's quality of life and may prolong survival.
Blood transfusions — If a person's red blood cell or platelet count becomes dangerously low, it is possible to give donated blood. A person may donate whole blood or single components, such as red blood cells or platelets. All donated blood and blood products are tested for infectious diseases. Thus, the risk of developing an infection as a result of transfused blood products is now very low. (See "Patient information: Blood donation and transfusion (Beyond the Basics)".)
- Red blood cells — Transfusions of red blood cells may be needed to treat signs or symptoms of anemia, including feeling tired or short of breath. If frequent or multiple transfusions of red blood cells are needed, iron overload may occur, which might lead to organ damage. Although controversial, some investigators believe that concern about iron overload should not occur until the patient has received approximately 30 units of packed red blood cells. A treatment called iron chelation may be recommended to remove this excessive iron from the body. Iron chelation treatments can be taken by mouth or as an injection under the skin or into a vein. These treatments have relatively few side effects, although it is unclear if their use prolongs life or improves its quality.
- Platelets — Transfusions of platelets may be needed to prevent or treat bleeding problems caused by too few platelets.
Hematopoietic growth factors — Hematopoietic growth factors are proteins that promote the growth and development of blood cells. The use of growth factors may reduce a person's need for blood transfusions. However, many people with MDS do not respond normally to hematopoietic growth factors because of the bone marrow's defective production of blood cells.
- Recombinant human granulocyte colony-stimulating factor (G-CSF, Neupogen) or recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate white blood cell (granulocyte) production, and may raise the patient's white blood cell count. Use of G-CSF alone is not recommended, except perhaps in the setting of severe infection.
- Recombinant human erythropoietin (EPO, Procrit, Epogen) promotes the growth of red cells, and decreases the need for red cell transfusions in 20 percent of MDS patients.
Usually, EPO is given alone initially. However, both growth factors are given as combination therapy in some settings.
Low intensity chemotherapy — Chemotherapy medications in MDS aim to change bone marrow cells to develop more normally, allowing for improved production of red cells, white cells, and platelets. Low doses of a single chemotherapy drug may be recommended for people with lower risk MDS or for people with intermediate or high IPSS scores who cannot tolerate high intensity chemotherapy or bone marrow transplantation.
- Azacitidine — Azacitidine (Vidaza) may increase survival and improve quality of life when compared with supportive treatments alone. Azacitidine is often given to patients with higher risk MDS. While a trial randomizing such patients to “best supportive care” (principally transfusions) or azacitidine found that survival was longer in the azacitidine group, the median improvement was only about six to nine months.
- Decitabine — Decitabine (Dacogen) is similar to azacitidine and appears to increase rates of complete remission. Complete remission means that there are no detectable blasts in the blood or bone marrow and that the bone marrow is functioning normally.
- Lenalidomide — Lenalidomide, a thalidomide-like drug, is particularly effective for people with anemia and lower risk MDS with abnormalities of chromosome 5 (called the 5q minus syndrome). Such patients may no longer require red blood cell transfusions after treatment with this agent.
Immunosuppressive drugs — In some patients with MDS, the immune system causes the bone marrow to slow production of blood cells. This may be especially true in people with a reduced number of cells in the bone marrow (called marrow hypoplasia).
Some of these patients, particularly those who are younger, with early stage disease and a reduced cell content of the bone marrow, respond to immunosuppressive therapies, which counter this immune attack on the bone marrow, with a resulting increased effective blood cell production. Use of an immunosuppressive therapy may allow between 50 to 60 percent of people who have the HLA DR2 tissue type to discontinue red blood cell transfusions.
Examples of immunosuppressive therapies include antithymocyte globulin (ATG) and cyclosporine. ATG is usually given into a vein once per day for four days while cyclosporine is usually taken by mouth twice per day for as long as it is effective.
Most everyone who is treated with ATG develops serum sickness, which causes hives, swelling, and fever. This reaction can be minimized by giving steroid treatment along with the ATG.
HIGH INTENSITY TREATMENTS
High intensity chemotherapy — Patients with intermediate or high risk type MDS may be treated with a chemotherapy regimen similar to that used for treatment of acute myeloid leukemia. In this group, chemotherapy is used to destroy abnormal cells or prevent them from growing. However, this treatment is only recommended if the person is relatively young (eg, <60 years), with a good performance status and normal cytogenetics. High intensity chemotherapy may also be recommended for a person who is eligible for bone marrow (stem cell) transplantation but who has no eligible donor. (See "Patient information: Acute myeloid leukemia (AML) treatment in adults (Beyond the Basics)".)
High intensity chemotherapy is not generally recommended for people with a poor performance status, particularly if they are older than 65, or patients age >75. In this group, the expected benefit (prolonged survival) may not be worth the anticipated discomfort, hospitalization, or risk of dying from the toxicity of chemotherapy. The exception would be if the patient were placed on a trial of an investigational therapy with benefits that might plausibly justify the risk.
In some patients, supportive care can provide benefits that are equal to standard chemotherapy, with a lower risk of complications or toxicity. It should be stressed, however, that neither alternative is satisfactory prompting interest in clinical trials, many of which are ongoing. Some people do better with an approach that treats MDS-related problems, such as infection or anemia, as they occur, rather than trying to cure the disease. Transfusions and antibiotics can be given as needed in place of more aggressive forms of therapy.
Blood and bone marrow transplantation — Bone marrow transplantation (also called hematopoietic stem cell transplantation) is the only known treatment for MDS that has the potential to induce long-term remission or cure. However, transplantation involves the use of high intensity chemotherapy, sometimes with whole body radiation, to eliminate all dividing cells in the bone marrow. Unfortunately, the risks of treatment may be greater than the benefits in some situations.
In the past, patients over age 50 were not considered for bone marrow transplantation, mostly due to the risk of transplant-related complications. Improvements have allowed the upper age limit for such transplantation to expand to people age 65 or more. However, approximately 75 percent of patients with MDS are older than 60 at diagnosis, so conventional transplantation can only be offered to a minority of individuals. (See "Patient information: Bone marrow transplantation (stem cell transplantation) (Beyond the Basics)".)
For treatment of MDS, the optimal source of stem cells is a brother or sister with a similar genetic makeup (ie, a matched related donor). In general, parents, children, and relatives are not suitable donors, since they do not share the same parents and therefore do not have the same genetic material. Improvements in the ability to match unrelated donors has improved over the years and allowed for the transplantation of persons without a matched related donor. A donor's blood (peripheral blood stem cells) has largely replaced bone marrow the source of stem cells.
Use of reduced intensity chemotherapy treatment before transplantation may allow some patients with MDS, who would not otherwise be eligible, to undergo transplantation with a lower incidence of transplant-related complications. Reduced intensity regimens use less intensive chemotherapy with low dose or no radiation before transplantation with matched stem cells.
Transplantation is recommended for people with higher risk MDS who are under the age of 60 and who have a tissue-matched sibling donor, but not for people with lower risk disease. Although there is a significant chance of cure after bone marrow transplantation in low risk patients (approximately 60 percent), transplant-related deaths and the relapse rate at five years are also high (as high as 40 percent).
For people who are diagnosed with MDS, the average length of survival depends upon the IPSS or IPSS-R risk category, presence of underlying medical problems, and age. It is important to remember that these numbers represent averages, and do not necessarily predict what will happen in your situation. There is considerable variation from patient to patient, especially in the low-risk group.
Many patients will be asked about enrolling in a clinical (research) trial. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask your doctor for more information, or read about clinical trials at:
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient information: Myelodysplastic syndromes (MDS) (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Acute myeloid leukemia (AML) treatment in adults (Beyond the Basics)
Patient information: Blood donation and transfusion (Beyond the Basics)
Patient information: Bone marrow transplantation (stem cell transplantation) (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Clinical manifestations and diagnosis of the myelodysplastic syndromes
Cytogenetics and molecular genetics of myelodysplastic syndromes
Hematopoietic cell transplantation for Diamond-Blackfan anemia and the myelodysplastic syndromes in children
Hematopoietic cell transplantation in myelodysplastic syndromes
Overview of the treatment of myelodysplastic syndromes
The following organizations also provide reliable health information.
- National Library of Medicine
- The Leukemia & Lymphoma Society
- The National Cancer Institute
- National Marrow Donor Program
- The American Society of Clinical Oncology
- The Aplastic Anemia & MDS International Foundation