Myelodysplastic Syndromes (MDS)
What Is MDS?
Myelodysplastic syndromes (MDS) are a group of rare blood cancers that affect the bone marrow. They occur when stem cells (immature cells) in the bone marrow do not age or develop in a normal way. They can become abnormal. The abnormal cells stay in the bone marrow. As a result, the bone marrow does not work correctly because it is not able to make enough healthy blood cells. This causes blood cell counts to become low.
Over time, the body makes fewer and fewer blood cells. As this occurs, symptoms can become worse and potentially life-threatening. MDS often affects red blood cells, but it can affect white blood cells or platelets too. Nearly one-third of people who have MDS go on to develop acute myeloid leukemia (AML).
Some people develop MDS following treatment for another cancer. When MDS is caused by cancer or other medical treatment, it is considered “secondary MDS.” MDS without a known cause is called primary or de novo MDS. Around 80% of people with MDS have primary MDS.
Because MDS is a group of diseases, the symptoms and outlook can vary a lot. Finding a treatment team that is experienced with MDS is very important.
There are 6 main subtypes of MDS. The subtype affects the symptoms you may have, how the disease should be treated, and how well treatment might work. The subtypes are:
- MDS with single lineage dysplasia (MDS-SLD)
- MDS with multilineage dysplasia (MDS-MLD)
- MDS with ring sideroblasts (MDS-RS) – includes MDS-RS-SLD and MDS-RS-MLD
- MDS with excess blasts (MDS-EB) – includes MDS-EB1 and MDS-EB2
- MDS with isolated del(5q)
- MDS, unclassifiable (MDS-U)
The cause of MDS is mostly unknown, but there are some known risk factors. A risk factor is something that increases the risk of getting a disease. Risk factors for MDS include:
- Age – Most people are over 65 when they develop MDS, but it can affect younger people too.
- Sex – People who were born male are more likely to get MDS.
- Exposure to radiation – If you live or work near high radiation, you may have a higher risk of MDS.
- Exposure to other chemicals or environmental hazards – Living or working near tobacco smoke, benzene, insecticides, and other chemicals can increase your risk.
- Smoking – People who smoke cigarettes are more likely to get MDS.
- Family history – MDS is not inherited. Yet, it is sometimes more common in some families. This is still being studied. Doctors have yet to find one gene or cause that is linked to higher risk.
- Rare bone marrow conditions – People with certain rare diseases that run in families are more likely to develop MDS. These include Fanconi anemia and Familial aplastic anemia, for example.
- Previous cancer treatment – MDS occasionally occurs because of prior cancer treatment. It can show up years after chemotherapy or radiation. Around 20% of people with MDS develop MDS due to previous cancer treatment. However, most people who are treated for cancer do not develop MDS.
Signs & Symptoms
Not everyone with MDS has signs or symptoms at the time of diagnosis. Those who do may notice the following:
- Shortness of breath
- Bone pain
- Easy bruising or bleeding
- Frequent infections
Diagnosis & Treatment Planning
MDS can be difficult to diagnose. Some people with MDS do not have any symptoms. The symptoms that may present are the same as those of other diseases. For this reason, diagnosis may involve ruling out other diseases.
The first sign of MDS may show up in low blood counts, found through blood tests. Your doctor may order a complete blood count (CBC) because you have symptoms or as part of a routine check-up.
MDS is a group of diseases. Your doctor will need to determine the subtype of MDS before starting treatment. The following tests may be used to diagnose MDS and to determine the subtype:
- Complete blood count – This shows the number of red blood cells, white blood cells, and platelets.
- Blood smear – This test provides a closer look at the blood cells.
- Bone marrow aspiration and biopsy – Your doctor will insert a needle into your hipbone to get a sample of liquid or tissue from the bone marrow. The removal of liquid is an aspiration. The removal of tissue is a biopsy. These 2 tests are usually done at the same time.
Bone marrow samples are sent to a lab for analysis. The following approaches may be used:
- Flow cytometry
- Cytogenetic testing or karyotyping
- Fluorescence in situ hybridization (FISH)
- Molecular tests
This test is run on special equipment to determine if blood cells in the bone marrow are maturing in a normal way. It also provides an approximate count of the immature blood cells. It can also provide information on cell characteristics, such as markers on cells.
This test looks at the cells of the bone marrow. Specifically, doctors examine the chromosomes inside the cells to see if anything looks abnormal. Each person’s cells have 23 pairs of chromosomes. It is common to see certain pairs missing or rearranged in the cells affected by MDS.
This lab test looks at differences in chromosomes that are common in people with MDS. The results come back faster than results of some other tests.
This test looks at the markers on cells. It can be used to see which markers are present on the cells and the portion of cells that have them.
These tests look for mutations in the genes or proteins of the bone marrow cells.
MDS is harder to understand than some cancers, and staging is done very differently than most cancers. Different lab tests will be needed for a complete diagnosis, and some may need to be repeated. Not all tests are available at every hospital. You may want to get a second opinion from an academic medical center or National Cancer Institute-approved cancer center before starting treatment.
The goal of staging is to learn the subtype and the risk score. In order to stage MDS, your doctor will look at:
- The percentage of immature blood cells (blasts)
- The blood counts that are affected – red, white, or platelet
- The abnormal cells – how many and what they look like
- Gene changes within the cells
A final diagnosis will answer these 3 questions:
- Is this primary or secondary MDS? Primary has no known cause. Secondary is an outcome of prior cancer treatment.
- What is the World Health Organization (WHO) subtype? The subtype is based on whether red or white blood cells, or platelets, are affected. MDS can affect one, two, or all blood cell counts. The subtype also describes percentage of blood cells that are affected and how they are affected, and whether certain chromosome changes are detected. The subtypes are:
- MDS with single lineage dysplasia (MDS-SLD) – This is a less common, more mild form of MDS. Some people with this subtype do not need treatment.
- MDS with multilineage dysplasia (MDS-MLD) – This is the most common subtype of MDS. It may develop into acute myeloid leukemia (AML).
- MDS with ring sideroblasts (MDS-RS) – This subtype includes MDS-RS-SLD and MDS-RS-MLD. It is less common and less likely to turn into AML.
- MDS with excess blasts (MDS-EB) – This subtype includes MDS-EB1 and MDS-EB2. It is a more common subtype. Around 1 in 4 people with MDS have this subtype. It is also more likely to turn into AML.
- MDS with isolated del(5q) – This subtype is more common in older women and has better outcomes. It is less likely to turn into AML.
- MDS, unclassifiable (MDS-U) – This very rare subtype describes MDS that does not fit the definition of any of the other subtypes.
- What is the risk score? The Revised International Prognostic Scoring System (IPSS-R) is the system used to assign a risk score. The score describes how serious or advanced the disease is, so you might think of the risk score as a sort of “stage” of MDS. There are 5 ratings ranging from very low to very high. A lower score has a better outlook. A higher score means that the MDS is more advanced and will be harder to treat. A higher score also means that the MDS is more likely to turn into acute myeloid leukemia, a serious blood cancer.
Treatment options will depend on:
- The stage and subtype of your cancer
- Your general health
- If your tumor has certain biomarkers that make it likely to respond to certain treatments
As you plan your treatment, 2 things you will want to consider are:
- What is the goal of each treatment? This may be a cure, or it may be treatment to help you live longer with a good quality of life.
- What are the side effects of each treatment? Ask how side effects may affect your quality of life. Find out what you and your health care team can do to help you manage them.
Learn more about becoming an active member of your health care team, including choosing your cancer treatment team, getting a second opinion, and understanding your treatment goals and options.
Many genes and changes to genes can play a role in MDS. Doctors often test for these biomarkers as a standard part of MDS staging. The results inform treatment even though there may not be a drug to target the biomarkers that are found. However, there are exceptions:
- People with MDS with isolated del(5q) subtype may respond better to the drug lenalidomide (Revlimid).
- People whose MDS has the PDGFR biomarker may benefit from imatinib mesylate (Gleevec).
Treatment Options & Side Effects
MDS varies from person to person. Treatment is provided by a doctor who specializes in cancers, or who specializes only in blood cancers. They may be a hematologist or a hematologist/oncologist. The timing and type of treatment depends on both the subtype and the IPSS-R risk score (“the risk score”). Your lifestyle may influence your treatment choices as well.
The goals of treatment are to keep the disease from progressing or turning into leukemia, maintain or improve blood counts, and help you feel better. In some cases, you may not need to start treatment right away. When you do, it often involves chemotherapy. You may have the option to take a chemotherapy drug at home in pill form.
When the risk score is high, your doctor may recommend a stem cell transplant. This is the only possible cure for MDS, but it is not always possible or effective. In rare cases, immunotherapy or targeted therapy may be used. Check with your health care team about clinical trials that may be an option for you.
Many people with MDS receive supportive care. These treatments are designed to boost blood counts and reduce symptoms. They do not treat the cancer. They can take considerable time and interfere with everyday life. Supportive care may involve:
- Blood transfusions to boost blood counts and reduce symptoms – People with MDS sometimes get transfusions as often as every week or 2. A transfusion can take up to several hours. You may feel better soon after a transfusion.
- Antibiotics to treat infections – Low blood counts can lead to frequent infections.
- Growth factors – These drugs are used to increase the number of mature blood cells. Different drugs boost different types of blood cells.
- Erythropoiesis-stimulating agents (ESAs) – Stimulate the bone marrow to make new red blood cells
- Erythroid Maturation Agents (EMAs) - Causes red blood cells to mature
- Chelating agents – These drugs are used to reduce iron build-up that can be caused by having many transfusions.
People with MDS often experience ongoing symptoms including depression, anxiety, fatigue, bruising, bleeding, and pain or discomfort. Ask to see a doctor or other medical professional who specializes in palliative care. This person can provide care to help improve your quality of life.
Your treatment options may include:
- Stem Cell Transplant
- Active Surveillance
- Targeted Therapy
- Clinical Trials
- Palliative Care
Chemotherapy involves the use of drugs to destroy cancer cells. It is a systemic (whole body) treatment. It may be given by IV (through a vein), in pill form (by mouth), as an injection (a shot), applied directly on the skin into the area around the tumor, or placed directly into the tumor site. Most often, chemotherapy is given in an outpatient clinic. You will have a regular schedule of treatments for a set period of time.
A stem cell transplant (SCT) is an infusion of blood-forming cells (stem cells). It is not a surgery. The procedure has two parts. First, you will receive high doses of chemotherapy. This destroys blood cells. Next, stem cells are introduced into the bloodstream to replace blood cells. Bone marrow transplant is one kind of SCT. Sometimes patients serve as their own donors (autologous stem cell transplant). Other times, patients get stem cells from donors (allogeneic stem cell transplant).
With active surveillance (also called “watchful waiting”), you see a doctor regularly but don’t begin treatment until needed. Studies have shown that when there is no indication to start treatment, watchful waiting allows the patient to continue their lifestyle without causing their disease to progress more rapidly. Studies do not show any benefit to starting treatment before there is a need. Watchful waiting delays treatment-related side effects, while still allowing your treatment to begin when needed.
In rare cases, immunotherapy may be used to treat MDS. Immunotherapy uses the body’s natural defenses (the immune system) to find, attack, and kill cancer cells. One type of immunotherapy, monoclonal antibodies, may be used in combination with chemotherapy. Some immunotherapy treatments are available only through clinical trials.
Targeted therapy aims to more precisely attack cancer cells. These drugs target changes in the genes or proteins of cancer cells that help them grow, divide, and spread.
Be sure to ask about clinical trials. These are research studies to test new treatments or learn how to use current treatments better. In some cases, the treatments with the best chance of success may be available only through clinical trials. Trials are offered for many cancers, at many different stages. Everyone is not eligible for every trial. If you have cancer that has come back or spread, it is especially important to ask about clinical trials.
People with MDS often experience ongoing symptoms that lead to discomfort. Ask to see a doctor or other medical professional who specializes in palliative care. This person can provide care to help improve your quality of life.
Myelodysplastic syndromes (MDS) are rare and not well understood. Your general doctor may not even know very much about MDS. It is not unusual for people with MDS to feel confused about what is wrong with them, on top of other emotions common to cancer. Taking time to learn about MDS can help you feel more in control and better able to make decisions.
Treatment for MDS often involves many blood tests and transfusions. Same-day hospital visits may be long and frequent. You may find that taking care of your health takes a lot of time. The costs associated with transportation, missed time at work, childcare, and more may become burdensome.
For these reasons, it is a good idea to seek support right away. Try to connect with other people who have MDS through a support group or seek counseling from a professional familiar with MDS.
Top Terms to Know
These are just some of the new words you may hear when talking about MDS with your doctor. Be sure to write down others as they come up. Ask your doctor to spell and define them. Ask again if you are still unsure of what they mean.
Anemia – Low red blood cell count.
Blasts – Immature blood cells that, in some types of MDS, die in the bone marrow, leaving little room for healthy cells.
Bone Marrow – Soft, spongy tissue inside bones where blood cells are made.
Cytopenia (low blood cell count) – The subtype of MDS is determined by the number of cytopenias. This refers to how many of the 3 blood cell counts (white, red, and platelet) are low.
Dysplasia or Dysplastic cells – These words are used to describe cells that look abnormal under the microscope. The bone marrow of someone with MDS will show signs of dysplasia.
Port – A device placed under the skin to make it easier to give and receive blood, like during transfusions.
Refractory – Disease or condition that does not respond to treatment. “Refractory anemia” is used to describe some MDS subtypes.
Ring sideroblast – Cells that have rings of iron deposits in them.
Thrombocytopenia – Low platelet count.