MDS Overview
Myelodysplastic syndromes (MDS) occur in 5 of 100,000 people in the general population. However, MDS are much more common among people 70 years and older, occurring in 22 to 45 of 100,000, with the incidence rate continuing to increase with age.
If you have been diagnosed with MDS, you probably have many questions about it, how it is likely to be treated, and what happens when treatment is completed. The treatment summaries, which are based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), will help you understand the best available treatments for MDS. Talk to your doctors about these options so that together you can decide on a treatment plan that is right for you.
Background
Myelodysplastic syndromes (MDS) are diseases of the blood and bone marrow. Your bone marrow is responsible for making blood stem cells (immature cells) that develop into mature blood cells over time. Blood stem cells can become 3 types of mature blood cells: red blood cells, white blood cells, and platelets. Red blood cells carry oxygen to all tissues of the body, white blood cells fight infection, and platelets help prevent bleeding by helping blood to clot.
In MDS, the blood stem cells do not mature properly into healthy red blood cells, white blood cells, or platelets. The immature cells in the bone marrow (some of which are stem cells) are called blasts. The blood cells that develop in MDS do not function normally and either die in the bone marrow or have decreased production. In MDS there are generally too few of one or more types of healthy blood cells in the bone marrow or blood.
There are 5 subtypes of MDS:
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Refractory anemia
: Too few red blood cells in the blood, but the numbers of white blood cells and platelets are normal
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Refractory anemia with ring sideroblasts: Too few red blood cells in the blood, and the red blood cells have too much iron
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Refractory anemia with excess blasts: Too few red blood cells in the blood and too many blasts in the bone marrow; there may be decreases in the white blood cells and platelets
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Refractory anemia with excess blasts in transformation: Too few red blood cells, white blood cells, and platelets in the blood; very high excess of blasts in bone marrow
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Chronic myelomonocytic leukemia (CMML): Too many cells in the blood called monocytes; the white blood count may be low normal or high; patients may have anemia and/or low platelets
MDS can also become acute myeloid leukemia (AML; called transformed AML). This transformation occurs in about 30% of patients at various intervals after diagnosis. The different subtypes of MDS have different rates of transformation. Transformed AML is much less responsive to chemotherapy than de novo (meaning the first occurrence of cancer in the body) AML. Depending on the way your doctor characterizes the disease, AML is diagnosed if the number of blasts in the marrow is greater than either 20% or 30%.
Diagnosing MDS
Although MDS often do not cause early symptoms and are commonly found during a routine blood test, symptoms can include:
- Shortness of breath
- Weakness
- Paleness
- Bruising easily
- Bleeding easily
- Fever
- Frequent infections
Most MDS cases occur with no known cause, but there are several known risk factors for developing MDS, including:
- Male gender
- White race
- Age older than 60 years
- Past treatment with chemotherapy or radiation therapy
- Exposure to certain chemicals, including tobacco smoke, pesticides, and organic solvents
- Exposure to heavy metals, such as mercury or lead
Staging
In most cancers, a formal system called staging is used to identify how early or advanced your cancer is. No such staging exists for MDS; instead, a system of stratifying the disease based on risk—called the International Prognostic Scoring System (IPSS)--is used to help determine whether MDS is early, intermediate, or advanced. This risk-based stratification system is based on 3 variables:
- Percentage of bone marrow blasts
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Cytogenetics (how the DNA in the chromosomes of your blood cells has changed)
- Number of blood cell types that are unhealthy (lower than normal)
Each of these variables is given a score and, based on this score, patients are stratified into 4 distinct risk categories: low, intermediate-1 (INT-1), intermediate-2 (INT-2), and high. For treatment purposes, the NCCN Guidelines™ divide the 4 risk groups into 2 groups: a lower-risk group (including low- and INT-1 risk patients) and a higher-risk group (INT-2 and high-risk patients). These risk groups are used to both help your doctors make treatment decisions and provide you and your doctors with information about what typically happens to patients with cancers most like yours.
For your doctor to determine your risk group, you will need to undergo several tests. These may include:
- A thorough physical exam, which will include several questions about any symptoms you might have experienced, your general health, and your medical history
- Blood tests
- Peripheral blood smear to look for visual changes in blood cells
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Bone marrow aspiration and biopsy
- Cytogenetic analysis (study of chromosomes) to look for changes in the chromosomes of your bone marrow cells
Blood count stability is used to distinguish MDS from evolving AML, and therefore your doctor will monitor your blood work closely.
Treatment of MDS
A number of treatments are available for MDS patients. No single treatment is right for everyone. You can help make the best decision by discussing the benefits, risks, and possible side effects of each treatment described below with your doctor. The goals of treatment for patients with MDS are to ease the symptoms, prolong survival, and provide major control of the disease.
Myelodysplastic syndromes treatment involves several specialists who plan and work as a team to coordinate your care, and often uses a combination of several approaches. This generally includes doctors and nurses.
Your doctor should provide you with a care plan explaining what treatments you will have, when and how often they will occur, and what side effects you may experience.
Some side effects can be anticipated, and you can receive treatment to reduce their severity.
Some treatments for MDS have been approved by the Federal Drug Administration (FDA) and are commercially available, and these are used for some patients. For other patients, whose disease has not responded to standard types of treatment, investigational treatment may be available. If you are to receive investigational treatment, you will be asked to review and sign an informed consent document indicating that the treatment has been discussed with you, you have been told what to expect, and that you understand these issues.
It is very important that you ask your doctor or nurse every question you have. MDS and its treatment are complicated, and most patients have questions.
Treatment options are based primarily on your risk status, but your age and performance status are also critical to determining your ability to tolerate certain intensive treatments.
In general, treatments rely on the following options, often in combination:
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Chemotherapy: drugs used to kill or slow the growth of immature blood cells
- Biologic response modifiers: drugs used to stimulate the immune system to help it do its job more effectively
- Immunosuppressive therapy: drugs used to suppress an abnormality of the immune system in certain patients and allow the bone marrow to make more blood cells
- Supportive care: such as blood transfusions (red blood cells or platelets), iron-chelation therapy, antibiotics, and cytokine therapy with growth factors (see Supportive Care below)
- Hematopoietic stem cell transplant: bone marrow cells are destroyed by chemotherapy and then replaced with stem cells from a tissue-matched donor
- Clinical trial: investigational drugs and protocols are used
Treatment for Lower-Risk MDS
In part, your treatment will depend on which type of blood cell is affected:
Red Blood Cells: Anemia
If you are anemic and have lower-risk MDS, one of the following treatment approaches may be appropriate for you:
- MDS patients with anemia caused by low levels of serum erythropoietin (Epo), may be treated with an erythropoietin stimulating agent (ESA). Some patients may also need white blood cell growth factors (such as G-CSF) to increase their number of white blood cells along with ESAs to increase their blood count. This type of treatment will help boost the number of red blood cells and will generally decrease some of the symptoms of MDS (for example, fatigue).
- Patients with anemia and deletion of part of chromosome 5 (called 5q- syndrome), with or without additional cytogenetic abnormalities, are usually effectively treated with lenalidomide, a biologic response modifier.
- Patients who have an adequate amount of erythropoietin but are still anemic may be treated with immunosuppressive drugs, such as antithymocyte or cyclosporin A, which prevent or inhibit immune system activity. Immunosuppressive therapy is a not a treatment option for everyone. Immunosuppressive therapy is generally an option for individuals younger than 60 or those with certain cytogenetic markers (such as HLA-DR15 and PNH clone).
- Patients whose disease does not respond to the above treatments or who do not qualify for immunosuppressive therapy have additional treatment options. Chemotherapy with hypomethylating agents that slow cell growth, such as azacytidine or decitabine, is a possible treatment option. Lenalidomide therapy is also an option.
Additional treatments are available for anemic lower-risk MDS patients whose disease does not respond to earlier treatments. Patients should consider enrolling in a clinical trial to be treated with new and investigational therapies. Lower-risk MDS patients may be considered candidates for a hematopoietic stem cell transplant if they experience severe cytopenias (anemia, thrombocytopenia, and neutropenia) that do not respond to any of the treatment mentioned above.
Platelets and White Blood Cells: Thrombocytopenia and Neutropenia
Lower-risk patients with thrombocytopenia or neutropenia may be treated using chemotherapy with azacytidine or decitabine. For patients whose disease does not respond to chemotherapy, immunosuppressive therapy may be considered if their doctors think they are likely to respond to it, or they may be candidates for an allogeneic stem cell transplant, in which they receive blood-forming stem cells from a genetically similar donor. All patients are encouraged to enroll in clinical trials.
Treatment for Higher-Risk MDS
Treatment for higher-risk patients depends on whether they are candidates for intensive therapy (allogeneic hematopoietic stem cell transplant or intensive chemotherapy). Factors that help determine this include:
- Age
- Performance status
- Other health problems
- Mental well-being
- The availability of a suitable stem cell donor and caregiver
- Patient preference
Hematopoietic stem cell transplant is a very intense procedure and you will need someone to help take care of you during and after this treatment.
High-Intensity Treatment
High-intensity treatment consists of hematopoietic stem cell transplant or intensive chemotherapy.
Low-Intensity Treatment
If you are not a candidate for high-intensity therapy, your treatment could consist of chemotherapy with azacytidine or decitabine, or enrollment in a clinical trial.
Treatment for Both Lower- and Higher-Risk MDS
Allogeneic stem cell transplants and supportive care are treatment options for both lower- and higher-risk MDS.
Allogeneic Stem Cell Transplants
Transplants have many potential side effects but may cure the disease. High-dose chemotherapy is used to kill the MDS (potentially leukemic) cells, but the dose is so high that it kills other rapidly dividing normal cells in your body. For example, blood cells that are responsible for your immune responses are destroyed. These blood cells are then replaced with an infusion of blood and marrow from a closely matched donor. These new cells seed (stimulate) your own bone marrow, and your body starts making new blood cells.
Therefore, to have an allogeneic stem cell transplant, you must have a donor who is a close match to you. Most frequently, this is a close relative, and siblings are common donors. Some centers will also perform stem cell transplants with unrelated donors. This is called a matched unrelated donor transplant. If a donor is not immediately available, treatment with chemotherapy agents such as azacytidine or decitabine can be used as an interim measure until a donor is located.
In addition, your bone marrow blast count must be low enough to attempt the transplant. If your blast count is too high, you must first have chemotherapy to lower the number of blasts in your bone marrow.
Once your blast count is in the right range and you have a donor, you will receive high-dose chemotherapy that wipes out your own developing blood cells in the bone marrow along with the cancer cells. This is called conditioning.
There are 2 different conditioning regimens: 1) standard, or myeloablative, and 2) non-myeloablative. Myeloablative conditioning destroys all bone marrow cells and is harder on the patient; therefore, it is often used on younger patients. Non-myeloablative conditioning uses lower-intensity chemotherapy that is not strong enough to destroy all bone marrow cells and is an option for patients who are not considered candidates for standard conditioning, such as those who are older.
After conditioning is complete, new stem cells are infused. These cells begin to grow and divide in your bone marrow, and grow new blood cells. Because of the risks associated with this treatment and the possibility of rejection of the new stem cells, the decision to pursue this option must be made after careful discussion with your doctor.
A major side effect of the transplant is called graft versus host disease (GVHD). In this condition, the donor bone marrow cells contain cells in addition to stem cells that act against the host (recipient’s) cells as well as against the MDS cells. As a result, major immunologic defects may develop, making the recipient vulnerable to infections. These immunologic defects and the GVHD itself require and receive specific types of treatment. Transplants should be performed at centers specializing in this complex procedure.
Supportive Care
All patients should also receive supportive care. Supportive care consists of:
- Red blood cell transfusions for symptomatic anemia
- Platelet transfusions for bleeding problems
- Iron chelation therapy to reduce excess storage of iron and prevent iron toxicity; this may be considered if you have received more than 20 to 30 red blood cell transfusions and many more are anticipated
- Antibiotics as needed for treating infections
- Cytokine therapy, such as ESAs to increase the number of red blood cells your bone marrow is making, or G-CSF, such as filgrastim (Neupogen), to increase the number of white blood cells
Prognosis
In determining a prognosis—the likely course or outcome of a disease and its treatment—a doctor may look at survival statistics taken from studies of large groups of MDS patients. However, such statistics:
- Are estimates only
- Can vary widely with each MDS stage
- Are sometimes based on older data that do not reflect recent advances in treatment options
- Cannot be used to precisely predict your survival
Your individual prognosis will be affected by many factors, including:
- Your age
- Your overall health, including other diseases you have
- The risk category (in the IPSS) of your disease
- Your response to the treatment(s) being used
New therapies and combinations of therapies are enabling people with MDS to live longer, with better quality lives than ever before. You may want to find out whether you are eligible to participate in a clinical trial, in which new and experimental therapies are used and may be compared to standard treatments.
Life After Treatment
During treatment and once your treatment is completed, you will need to see your doctor for follow-up visits at regular intervals to make sure that you remain healthy and so that any long-term effects of cancer or its treatment can be attended to.