Myelodysplastic syndromes (MDS) are a rare group of blood disorders characterized by abnormal development of blood cells within the bone marrow. Individuals with MDS have abnormally low blood cell levels (low blood counts).
Signs and symptoms associated with MDS include dizziness, fatigue, weakness, shortness of breath, bruising and bleeding, frequent infections, and headaches. In some cases, MDS may progress to bone marrow failure or an acute leukemia. The exact cause of MDS is unknown. It sometimes runs in families, but no disease-causing gene has been identified. Treatment depends on the affected individual's age, general health, and type of MDS and may include red cell and/or platelet transfusions and antibiotics.
Myelodysplastic syndromes rarely cause signs or symptoms in the early stages of the disease. In time, myelodysplastic syndromes may cause:
- Shortness of breath
- Unusual paleness (pallor) due to anemia
- Easy or unusual bruising or bleeding
- Pinpoint-sized red spots just beneath your skin caused by bleeding (petechiae)
- Frequent infections
The exact cause of MDS is unknown. MDS is thought to arise from mutations in the multi-potent bone marrow stem cell, but the specific defects responsible for these diseases remain poorly understood. Differentiation of blood precursor cells is impaired, and there is a significant increase in levels of apoptotic cell death in bone marrow cells. Clonal expansion of the abnormal cells results in the production of cells which have lost the ability to differentiate. If the overall percentage of bone marrow blasts rises over a particular cutoff of 20 % to 30 %, then transformation to acute myelogenous leukemia (AML) is said to have occurred.
Risk factors for myelodysplastic syndromes are an age over 60 years, being male, the treatment with chemotherapy or radiation, exposure to certain chemicals (tobacco smoke, pesticides, industrial chemicals such as benzene) and exposure to heavy metals like lead and mercury.
There are six subtypes of myelodysplastic syndromes, depending on the cell types that are affected:
- Refractory cytopenia with unilineage dysplasia. In this type, one or two blood cell types are low in number — most commonly, the red blood cells are affected. Also, one type of blood cell appears abnormal under the microscope.
- Refractory anemia with ringed sideroblasts. This differs from refractory anemia in that existing red blood cells contain excess amounts of iron (ringed sideroblasts).
- Refractory cytopenia with multilineage dysplasia. In this myelodysplastic syndrome, two of the three types of blood cells are abnormal, and less than 1 percent of the cells in the bloodstream are immature cells (blasts).
- Refractory anemia with excess blasts — types 1 and 2. In both these syndromes, any of the three types of cells — red blood cells, white blood cells or platelets — may be low in number and appear abnormal under a microscope.
- Myelodysplastic syndrome, unclassified. In this uncommon syndrome, there are reduced numbers of one of the three types of mature blood cells, and either the white blood cells or platelets look abnormal under a microscope.
- Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality. People with this syndrome have low numbers of red blood cells, and the cells have a specific defect in their DNA.
Factors that may increase your risk of myelodysplastic syndromes include:
- Older age. Most people with myelodysplastic syndromes are adults older than 60.
- Treatment with chemotherapy or radiation. Your risk of myelodysplastic syndromes is increased if you received chemotherapy or radiation therapy, both of which are commonly used to treat cancer.
- Exposure to certain chemicals. Chemicals linked to myelodysplastic syndromes include tobacco smoke, pesticides and industrial chemicals, such as benzene.
- Exposure to heavy metals. Heavy metals linked to myelodysplastic syndromes include lead and mercury.
Smoking is linked to the development of leukemia and myelodysplastic syndromes (MDS), not smoking can lower the risk of this disease. On other hand, nonsmokers are also less likely than smokers to develop many other types of cancers, as well as heart disease, stroke, and other diseases.
MDS must be differentiated from a lack of red blood cells (anemia), a lack of platelets (thrombocytopenia), and/or decrease in the number of white blood cells (leukopenia). Usually, the elimination of other causes of these deficiencies, along with an increased numbers of immature cells in the bone marrow (dysplastic bone marrow), is required to diagnose a myelodysplastic syndrome. A typical investigation includes different blood tests, a bone marrow biopsy and cytogenetic tests.
A routine blood test can be used to determine the count and balance of the different blood cell types. The blood film morphology can provide clues about hemolytic anemia, clumping of the platelets leading to spurious thrombocytopenia, or leukemia.
Blood tests can also be used to measure the vitamin levels in the body. This is needed to make sure that the symptoms are not being caused by some other condition, such as lupus, hepatitis, B12, folate, or other vitamin deficiencies, renal failure or heart failure, HIV, hemolytic anemia, monoclonal gammopathy.
Finally, most patients will have a bone marrow sample taken by a hematopathologist to confirm the diagnosis. The sample is taken from the hipbone and as the procedure is quite uncomfortable, so patients are given local anesthetic. Almost all people with MDS have a particularly overactive bone marrow with an increased numbers of immature cells (dysplastic bone marrow). Patients with one form of MDS, called hypoplastic MDS, have an under active bone marrow.
Tests that detect genetic changes in cells (cytogenetic tests) are used to identify abnormalities that occur once the condition has developed.
The outlook in MDS is variable, with ~30% of patients progressing to refractory acute myeloid leukemia. The median survival rate varies from years to months, depending on type. Stem cell transplantation offers cure, with survival rates of 50% at 3 years, although older patients do poorly.
Depending on the severity of MDS, the symptoms can be treated through supportive care or medications. In rare cases, MDS can be treated with chemotherapy or stem cell transplantations.
Supportive care, which helps with the prevention and relief of infections and treatment complications, is a major part of treatment for all patients with MDS. These include:
- Anaemia, for which patients are given blood transfusions and growth factors to boost the number of healthy red cells in their blood. Anaemic patients who have an under-active bone marrow may benefit from treatment that suppresses the immune system.
- Thrombocytopenia, which causes excessive bleeding, is treated with transfusion of platelets
- Infections, caused by too few white blood cells are treated with standard antibiotics.
Chemotherapy, a combination of anti-cancer drugs, is sometimes used to treat MDS. These drugs need to be taken in a precise sequence to have the best effect. The intensity and combination of drugs differ from patient to patient depending on their exact diagnosis and the severity of their condition. Some patients, whose condition is considered to be less serious, are not given any chemotherapy.
Stem cell transplant is an intensive treatment and the only potential cure for patients with MDS. During a bone marrow stem cell transplant, the defective blood cells are destroyed using powerful chemotherapy drugs. Then the abnormal bone marrow stem cells are replaced with healthy, donated cells (allogeneic transplant). Unfortunately, few people are candidates for this procedure because of the high risks involved in transplanting in older adults - those most likely to have myelodysplastic syndromes. Even among young, relatively healthy people, the number of transplant-related complications is high. Stem cell transplants work best and have fewer side effects if the stem cells are from a well-matched donor, such as a sibling. Unfortunately only a small minority of patients can be considered for transplants because it can be difficult to find a donor and the procedure is quite risky.
Some new drugs have shown promise in treating MDS. These include lenalidomide (Revlimid™) and azacitidine (Vidaza™).
Medications used to increase the number of healthy blood cells the body produces include:
- Medications that increase the number of blood cells the body makes. Called growth factors, these medications are artificial versions of substances found naturally in the bone marrow. Some growth factors, such as erythropoietin or darbepoietin, can reduce the need for blood transfusions by increasing red blood cells. Others may help prevent infections by increasing white blood cells in people with certain myelodysplastic syndromes.
- Medications that stimulate blood cells to mature, rather than remain immature. Medications such as azacitidine (Vidaza) and decitabine (Dacogen) may improve the quality of life of people with certain myelodysplastic syndromes and help delay progression to acute myelogenous leukemia. But these drugs aren't effective in all people, and some can cause further blood cell problems.
- Medications that suppress the immune system. Medications used to suppress the immune system may be used in certain myelodysplastic syndromes.
Medication for people with a certain genetic abnormality. If the myelodysplastic syndrome is associated with a genetic abnormality called isolated del(5q), the doctor may recommend lenalidomide (Revlimid). Lenalidomide may reduce the need for blood transfusions in people with this abnormality.
Refer to Research Publications.