Treatment options for MDS include:
- Stem cell transplant (SCT)
- Blood transfusions
- Hematopoietic growth factors
- Hypomethylating agents
- Immunomodulatory drugs (IMiDs)
Bone marrow is a soft, sponge-like material found inside certain bones, such as the heads of the femur and humerus, the sternum, and the pelvic bones. Bone marrow contains immature cells called stem cells. Some stem cells mature into white blood cells, red blood cells, and platelets, all of which are damaged in conditions like MDS and leukemia.
For a stem cell transplant, stem cells from the peripheral blood or bone marrow are collected (harvested) and placed in frozen storage prior to treatment of the cancer with high-dose chemotherapy. Once chemotherapy treatment is complete, the stem cells are put back into your body; they enter your blood stream and travel to your bone marrow where they replace damaged stem cells and begin to make healthy blood cells. If your own stem cells are used the transplant is called autologous. If a donor's cells are used, it is called an allogeneic transplant.
Most patients with MDS are not eligible for autologous transplants because their reserve of healthy stem cells is contaminated by damaged cells. However, younger people may be candidates for allogeneic transplantation.
Due to limitations, such as the advanced age of most MDS patients and the limited availability of related donors, this procedure is only done in about 5% of all patients with MDS.
Remission of the disease may be achieved in as many as 60% of patients with MDS using bone marrow transplant (BMT). The success of the treatment varies with the age and sex of the patient, the duration of the disease, the compatibility of the donor, and the overall risk rating of the patient. 4-year disease-free survival may run as low as 15%-20% depending on the donor match and the aggressiveness of the MDS.
Relapse rates differ among the classifications of MDS. Less than 1% of patients with refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) relapse within the first 2 years after BMT. This percentage is greater—25%-50%—among people with refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-t), and chronic myelomonocytic leukemia (CMML).
A common side effect of BMT from a donor (allogeneic transplant) is graft versus host disease (GVH). This occurs when white blood cells in the donor marrow identify the patient's cells as foreign and attack them. GVH may be severe or even fatal, even if the donation came from a matched related donor.
Matched related donors are available for only 30%-35% of qualified patients. For those who do not have a match in the family, options include using slightly mismatched related donors or matched unrelated donors. In both cases, the risk of GVH increases.
Blood has many components. If you are low in specific components, they may be isolated and transfused (given to you) to raise your low levels to normal. For example, anemia is treated with transfusions of red blood cells. The bleeding tendency caused by MDS is usually a result of a low level of platelets in your blood. Therefore, you could receive a transfusion of blood platelets.
To receive a blood transfusion, a needle is placed in one of your veins. A bag containing the blood product is hung on a pole nearby, and its contents are dripped slowly, intravenously (through the vein) into your bloodstream. You will be closely monitored for signs of a reaction.
Once the bag containing the blood product is empty, which takes 2-4 hours, the needle is removed from your arm.
Blood transfusions do not alter the natural course of your disease, but they do offer improvement of symptoms. Transfusions are almost always effective at improving your blood count. However, each blood component has a limited lifespan, so you may receive repeated transfusions during the course of your disease. In general, frequent transfusions increase the likelihood of becoming resistant to transfusions later on.
Possible side effects of blood transfusions include the following:
Transfusion reactions —The more transfusions you receive, the greater the chance that your immune system will respond to the new blood cells as though they are foreign and develop antibodies to them. These antibodies may attack the blood cells, causing a transfusion reaction. Such reactions may be severe. Symptoms include fever, chills, a rash, back pain, bloody urine, dizziness, or fainting.
Because the risk of becoming resistant increases with more transfusions, this treatment may not be used indefinitely in some people. While reactions may not occur, the blood products may no longer boost the blood counts after many transfusions.
Hemochromatosis — This is a condition of too much iron in the blood, which can result in iron being deposited in the skin and organs. Since red blood cells contain iron, repeated transfusions of red blood cells can store up enough iron to cause hemochromatosis. The liver, heart, and endocrine organs (such as the pancreas) can be damaged; heart failure and diabetes can result. Excess iron can be removed from the body with the drug deferoxamine, which is given intravenously; however, this is not a very efficient process.
Infection—The risk of transmission of infection through a transfusion is extremely low, but not impossible. Risks of transfusion of even a single unit of blood include transmission of hepatitis B and C, HIV (AIDS), and—rarely—other blood-born infections, such as malaria. In general, the risk of transfusion-related infection is far outweighed by the benefits. You should discuss this with your physician. Most centers will recommend that you read and sign an informed consent form before your transfusion so that you better understand the risks and benefits involved.
Hematopoietic Growth Factors
Hematopoietic growth factors are naturally occurring agents that stimulate the normal maturation process of blood stem cells:
- Erythropoietin (epoetin, Epogen, Procrit; darbepoetin alfa, Aranesp)
- Granulocyte-colony stimulating factor or G-CSF (filgrastim, Neupogen, pegfilgrastim, Neulasta)
- Granulocyte macrophage-colony stimulating factor or GM-CSF (sargramostim)
- The drug oprelvekin (Neumega) stimulated production of platelets
Epoetin is a man-made version of human erythropoietin. Erythropoietin promotes the maturation of red blood cells. G-CSF stimulates the maturation of a type of white blood cell called a neutrophil.
A small percentage of people with MDS may benefit from the strategic use of these agents. Administration of these agents is continuous for as long as benefits are derived. Epoetin is usually given either intravenously (into the vein) or subcutaneously (under the skin) weekly. Darbepoetin alfa may be given every 2-4 weeks intramuscularly (into the muscle). Filgrastim requires daily subcutaneous injection.
The use is the subject of investigation to determine just how beneficial they may be in all types of MDS; these agents should be used on a case-by-case basis.
These growth factors are often combined with chemotherapy in the hope that while the chemotherapy drugs are wiping out the diseased cells, the growth factors are encouraging the growth of normal cells to replace them.
Erythropoietin is effective in decreasing the need for transfusions, but it has no therapeutic effect on the natural history of the disease.
G-CSF may help resolve otherwise serious or lethal infections in patients with very low white blood cell counts. It may also be useful to prevent subsequent infections. Its effect on the natural history of MDS is the subject of investigation.
Possible side effects of erythropoietin include:
- Cough, sneezing, or sore throat
- Swelling of face, fingers, ankles, feet, or lower legs
- Weight gain
- High blood pressure if the hematocrit (percentage of packed red blood cells in a given sample of blood) rises too quickly or too high (unlikely in this disease)
Possible side effects of filgrastim include:
- Pain in arms or legs
- Pain in joints or muscles
- Pain in lower back or pelvis
- Skin rash or itching
Failure of cell differentiation (or maturation) is the primary defect in MDS. It has recently been discovered that certain chemicals, among them anticancer drugs, have the ability to promote cell differentiation.
2 hypomethylating agents are used in the treatment of MDS. They work on genes to slow cell growth and kill cancer cells. The 2 drugs used are decitabine (Dacogen) and azacytidine (Vidaza).
Other agents that are being studied for use as differentiation agents include vitamin A derivatives, vitamin D3, arsenicals, and alpha interferon.
Some patients have shown an improvement in blood counts with these drugs. Other positive findings include a reduced need for transfusions, a decreased risk of developing leukemia, and a longer life.
Danazol (Danocrine) is a synthetic male hormone used mostly for female disorders. It has produced some improvement in clotting and in anemia in MDS patients. Its use for the treatment of MDS is anecdotal but it may be of benefit in certain patients.
Studies are too limited to generalize the effectiveness of this treatment.
Side effects of danazol include:
- Blood clots
- Liver damage
- Brain damage
- Masculinizing effects
Thalidomide has been shown to decrease the need for blood transfusions in several studies. Thalidomide is given orally.
Studies are too limited to generalize the effectiveness of this treatment; however, reports have shown improvement in subsets of patients with MDS.
Side effects of thalidomide include the following:
- Blood clots, especially when combined with chemotherapy
- Fluid retention
Severe birth defects when taken during pregnancy
- Note: Thalidomide is severely restricted and should never be given to pregnant women.
Immunomodulatory drugs (IMiDs)
Immunomodulatory drugs (IMiDs) are a class of drugs that can modify or regulate the immune system. IMiDs are taken orally, and are similar in chemical structure to thalidomide. Lenalidomide, an IMiD, was approved by the FDA in 2005 to treat deletion 5q cytogenetic abnormality. This type of MDS causes patients to have low red blood cell counts that generally require blood transfusions.
Clinical trials have found that patients treated with lenalidomide no longer needed transfusions, most after 3 months of treatment. Patients remained transfusion-free for an average of 44 weeks.
Possible risks and side effects include the following:
- Severe, life-threatening birth defects or death of an unborn baby—Because lenalidomide is chemically similar to thalidomide, female patients must not get pregnant 4 weeks before treatment, must not take lenalidomide during pregnancy, and must not take the medication 4 weeks after pregnancy. Lenalidomide is only available through a restricted, risk-management distribution system called RevAssist.
- Low white blood cell count
- Low platelet count
- Blood clots in the veins and lungs
Dacogen was approved by the FDA in 2006 to treat all French-American-British (FAB) subtypes of MDS (for example, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts). It is also approved for intermediate-1, intermediate-2, and high-risk patients according to the International Prognostic Scoring System (IPSS).
The medication is administered through injection in 4 treatment cycles. Decitabine improves bone marrow functioning by helping to restore normal growth and differentiation of bone marrow cells, which increase red and white blood cell and/or platelet counts. Decitabine may also correct DNA abnormalities associated with MDS.
Phase II and Phase III trials of decitabine showed favorable responses in patients receiving decitabine and supportive care compared to patients only receiving supportive care. Patients receiving decitabine also had increased platelet counts.
Side effects for decitabine include:
- Harm to an unborn baby—Women should not become pregnant while being treated with decitabine, and men should not father a child while receiving decitabine and for 2 months after treatment ends.
- Low red blood cell count (anemia)
- Low white blood cell count (neutropenia)
- Low platelet count (thrombocytopenia)
When to Contact Your Healthcare Provider
Thoroughly discuss your treatments with your doctor so you know what to expect. Ask about side effects, and report any new symptoms or changes in your condition to your doctor.
- Reviewer: Mohei Abouzied, MD, FACP
- Review Date: 12/2014 -
- Update Date: 12/20/2014 -