Patient information: Myelodysplastic syndromes (MDS) in adults (Beyond the Basics)
- Elihu H Estey, MD
Elihu H Estey, MD
- University of Washington School of Medicine
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
MYELODYSPLASTIC SYNDROMES OVERVIEW
The myelodysplastic syndromes (MDS, myelodysplasia) are a group of blood disorders associated with abnormal blood cell production. Normally, blood cells (red cells, white cells, platelets) are produced in a controlled fashion by the bone marrow (the spongy, red tissue that fills the large bones). In MDS, the stem cells in the bone marrow have been damaged and do not function normally. As a result, one or more types of blood cells that they produce are abnormal. This can result in low blood counts and blood cells that do not function properly.
Some people have no symptoms when they are diagnosed with MDS. Others have symptoms related to low blood counts:
●Neutropenia (low numbers of neutrophils) – Neutrophils are a type of white blood cells that help to fight infection. People with neutropenia are more likely to get infections.
●Anemia (low numbers of red blood cells) – Red blood cells carry oxygen to our tissues. People without enough red cells may be pale and are often tired and short of breath. Anemia is the most common symptom of MDS.
●Thrombocytopenia (low numbers of platelets) – Platelets help blood to clot normally. People with low platelets have bleeding and spontaneous bruising.
MDS is a type of blood cancer that can be difficult to diagnose. In many ways, it acts like a type of chronic leukemia. However, a number of nonmalignant (benign) disorders can mimic the changes seen in MDS with low blood counts and abnormal appearance of blood and marrow cells. Through clinical tests, doctors can usually eliminate nonmalignant causes and establish a firm diagnosis of MDS. However, this may require a period of observation before the diagnosis can be confirmed.
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 of age when they are diagnosed with MDS, although it can develop during childhood.
More detailed information about MDS, written for healthcare providers, is available by subscription. (See 'Professional level information' below.)
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, or after having symptoms like easy bruising or unusual 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 blood cells, white blood cells (of which there are several different types), and platelets.
●A blood smear involves examining a small sample of blood under a microscope to determine the characteristics (number, size, shape, maturity, and type) of blood cells and whether they look normal.
●Cytogenetic analysis examines the blood or bone marrow cells for signs of genetic abnormalities in the chromosomes (chromosomes are the structures within cells that contain our genes). Researchers have discovered that the genetic makeup of the cells can vary, which can affect how a particular person responds to treatment. Interpretation of these studies is complicated. In general, outcomes are better for people with normal chromosomes and worse for people with complex changes in their chromosomes.
●The final diagnosis of MDS depends on examination of the cells in the bone marrow. 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 using special stains to look for abnormal and immature cells.
TYPES OF MYELODYSPLASTIC SYNDROME
MDS is a group of cancers of the blood and bone marrow with varying degrees of severity, need for treatment, and impact on life expectancy. MDS can be classified by pathologists into one of several subgroups based on features of the abnormal cells. The severity of a particular case can then be further delineated clinically using a prognostic scoring system.
This pathologic classification system is called the World Health Organization classification and criteria for the myelodysplastic syndromes. This system classifies cases based on the blood counts, the number of immature cells in the bone marrow (called blasts), and the results of cytogenetic studies (that look for chromosome abnormalities). A person's subgroup may change over time, as the disease progresses.
The clinical classification systems used for MDS are the original and revised International Prognostic Scoring Systems (IPSS and IPSS-R, respectively). These models consider the percentage of blasts in the bone marrow, the type of blood abnormality present, and a broader panel of cytogenetic abnormalities. Based on these criteria, the original IPSS calculates a person's numeric "score," which is then associated with one of four risk groups: low, intermediate-1, intermediate-2, or high. The IPSS-R works in a similar way, but defines five risk groups: very low, low, intermediate, high, and very high.
Treatment recommendations are based upon your 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 or her life expectancy may not exceed one to two years. However, it is important to remember that the IPSS (or IPSS-R) score cannot predict how long an individual person is going to survive; some people will live much longer and others much shorter than the risk group overall.
Other than stem cell (blood or bone marrow) transplantation, there is currently no proven cure for MDS; however, a number of treatment options are available to control symptoms, prevent complications of MDS, prolong survival, and improve quality of life. Not all people with MDS require immediate treatment. Immediate treatment is indicated for people with symptoms related to MDS, or, given that life expectancy is greatly decreased without treatment, for people with high- or very-high-risk MDS. People without symptoms and those with low-risk MDS are usually monitored closely for disease progression.
For people with symptoms, our treatment approach is similar to that proposed by the National Comprehensive Cancer Network (NCCN). We choose a treatment based upon the person’s age, performance status (a measure of how well a person can perform normal daily tasks), and disease characteristics such as the IPSS (or IPSS-R) risk score.
Treatment options — Treatment options for people with MDS typically fall into one of three categories:
●Supportive care – This includes the use of antibiotics for infection and transfusions for low blood counts. Supportive care is an important part of the management of all people with MDS. Immunizations against influenza and Pneumococcal pneumonia are recommended. (See 'Supportive treatments' below.)
●Low intensity treatment – This category includes those treatments less likely to produce serious treatment-related side effects and risks. They typically do not require hospitalization, and include the use of hematopoietic growth factors, low intensity chemotherapy, immunosuppressive treatments (which reduce the activity of the body’s immune system), or a thalidomide derivative. (See 'Low intensity treatments' below.)
●High intensity treatment – High intensity therapies include combination chemotherapy (similar to that used for acute leukemia) and bone marrow transplantation. These may require hospitalization, and have a higher risk of complications and even death. (See 'High intensity treatments' below.)
Treatment recommendations — Our general approach to the treatment of MDS is as follows:
●Supportive care is an important adjunct to the management of all patients with MDS. (See 'Supportive treatments' below.)
●People with lower risk MDS are generally treated with low intensity therapy or supportive care alone (see 'Low intensity treatments' below).
●People with higher risk MDS who are young and otherwise healthy are generally treated with high intensity therapies (see 'High intensity treatments' below).
●People with intermediate risk MDS can be treated with either approach.
None of the treatment options for MDS are truly satisfactory so there is great interest in clinical trials. Higher intensity treatment options do not always result in better outcomes. For some people, supportive care can provide benefits that are equal to standard chemotherapy, with a lower risk of complications or toxicity. In this way, 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.
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 older age of most people with MDS and the chronic nature of the disease, supportive care is an important part of treatment for all people. These treatments will not cure the disease, but 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 receive donated blood by transfusion. A healthy 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 contracting a disease as a result of transfused blood products is now extremely 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 (usually more than 30 transfusions), a problem called "iron overload" may occur, which might lead to organ damage. A treatment called "iron chelation" may be recommended to remove this excess iron from the body. Medication for 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 having too few platelets. In contrast to red blood cells, which can survive for 100 days, platelets survive for about eight days and so transfusions of platelets must be given more frequently.
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 (filgrastim, G-CSF, Neupogen, or Neulasta) or recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate white blood cell (granulocyte) production, and may raise the white blood cell count. Use of G-CSF alone is not recommended, except perhaps in the setting of severe infection.
●Recombinant human erythropoietin (Epoetin, EPO, Procrit, Epogen, darbepoetin) promotes the growth of red cells and decreases the need for red cell transfusions in 20 percent of people with MDS.
Usually, EPO is given alone initially. However, both growth factors are given as combination therapy in some settings.
Vaccinations and antibiotics — Vaccines are especially important for people with MDS. People with MDS are at higher risk of infections than other people, and vaccines help prevent infections. Only some vaccines are safe and appropriate for people with MDS.
People with MDS should have yearly influenza vaccines and a pneumococcal vaccine every five years. In general, people with MDS can get "inactivated vaccines," which are vaccines that contain dead copies of a virus. People with MDS usually should not get "live attenuated vaccines," which are vaccines that contain live but weakened copies of a virus.
People with MDS are treated with antibiotics when they have bacterial infections. Antibiotics are not usually given to prevent infection (as prophylaxis) unless they are receiving treatments that suppress their immune system further.
LOW INTENSITY TREATMENTS
Low intensity chemotherapy — Chemotherapy medications in MDS aim to change bone marrow cells to develop more normally, allowing for improved production of red blood cells, white blood 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-risk MDS who cannot tolerate high intensity chemotherapy or bone marrow transplantation.
●Azacitidine – Azacitidine (brand name: Vidaza) may increase survival and improve quality of life when compared with supportive treatments alone. Azacitidine is often given to people 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 (brand name: Dacogen) is similar to azacitidine and appears to produce similar degrees of improvement in median survival.
●Lenalidomide – Lenalidomide (brand name: Revlimid) is a thalidomide-like drug that is particularly effective for people with anemia and lower risk MDS with abnormalities of chromosome 5 (called the "5q minus syndrome"). Such people may no longer require red blood cell transfusions after treatment with this agent.
Immunosuppressive drugs — In some people 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 people (particularly those who are younger, with early stage disease and a reduced cell content of the bone marrow) respond to immunosuppressive therapies. These are treatments that counter MDS's immune attack on the bone marrow, resulting in increased effective blood cell production and a decreased need for 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 an allergic reaction called serum sickness, which causes hives, swelling, and fever. This reaction can be minimized by giving corticosteroid treatment with prednisone along with the ATG.
HIGH INTENSITY TREATMENTS
High intensity chemotherapy — People with intermediate- or high-risk type MDS may be treated with a chemotherapy regimen similar to that used for treatment of acute myeloid leukemia (AML). In this group, chemotherapy is used to destroy abnormal cells or prevent them from growing. High intensity chemotherapy is unlikely to cure MDS on its own. As such, high intensity chemotherapy is followed by blood or bone marrow transplant in patients who are eligible for transplant.
Intensive chemotherapy is only recommended if the person is relatively young (usually under 60 years of age), with a good performance status. (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 for anyone over the age of 75. For these people, the expected benefit (prolonged survival) may not be worth the anticipated discomfort, hospitalization, or risk of dying from the effects of chemotherapy. The exception would be if the person were placed on a trial of an investigational (new) therapy with benefits that might plausibly justify the risk.
Blood or bone marrow transplantation — Bone marrow transplantation (also called hematopoietic cell transplantation or stem cell transplantation) is the only known treatment for MDS that has the potential to induce long-term remission or cure. However, transplantation often 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, people over age 50 were rarely considered for 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 70 or more. However, approximately 75 percent of people with MDS are older than 60 at diagnosis, so conventional transplantation can only be recommended 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). The ability to match unrelated volunteer donors has improved over the years and allowed more people without a matched related donor to get a transplant. In many people, transplants from such matched unrelated donors may be as effective as those from matched sibling donors. A donor's blood (peripheral blood stem cells) has largely replaced bone marrow as the source of stem cells for transplantation.
Use of "reduced intensity" chemotherapy treatment before transplantation may allow some people with MDS, who would not otherwise be eligible, to undergo transplantation with fewer 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 younger people with higher risk MDS who have a matched 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 person to person, especially in the low-risk group. Your doctor can help you understand your situation and options.
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:
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/pre-act).
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.
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 and adolescents
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 American Society of Hematology
●The Leukemia & Lymphoma Society
●The National Cancer Institute
●National Marrow Donor Program
●The American Society of Clinical Oncology
●The Aplastic Anemia & MDS International Foundation
- Swerdlow SH, Campo E, Harris NL, et al. WHO classification of Tumors of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012; 120:2454.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.