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What is Myelodysplastic Syndrome ?
About the blood and bone marrow
The bone marrow is the soft, spongy tissue found in the center of large bones that stores immature cells called stem cells. Stem cells normally mature into white blood cells, red blood cells, and platelets during a process called hematopoiesis. In the body, white blood cells fight infections, red blood cells carry oxygen throughout the body, and platelets help the blood to clot.
About myelodysplastic syndromes
Myelodysplastic syndromes, also known as MDS, are a group of blood and bone marrow disorders. In MDS, stem cells do not mature normally, and the number of blasts (immature cells) and dysplastic (abnormally developed) cells increases. Also, the number of healthy mature cells decreases, meaning there are fewer normal red blood cells, white blood cells, and platelets. The numbers of blood cells are often called blood cell counts.
Because of the decrease in healthy cells, people with MDS often have anemia (a low red blood cell count), and may have neutropenia (a low white blood cell count) and thrombocytopenia (a low number of platelets). There may also be changes (abnormalities) to the chromosomes (long strands of genes) in the bone marrow cells.
There are several subtypes of MDS, and some subtypes of MDS may eventually turn into acute myeloid leukemia (AML), a cancer of the blood in which immature cells called blasts increase and grow uncontrollably.
A risk factor is anything that increases a person’s chance of developing a disease. Although risk factors often influence the development of MDS, most do not directly cause MDS. Some people with several risk factors never develop MDS, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.
The following factors may raise a person’s risk of developing MDS:
Age. MDS occurs most often in people older than 60 and is less common in younger people. MDS is rare in children.
Gender. Men develop MDS more often than women.
Exposure to environmental/occupational hazards. Long-term exposure to benzene or other toxins, such as tobacco smoke and insecticides, may increase the risk of developing MDS.
Previous chemotherapy or radiation treatment. Approximately 20% of people who develop MDS previously received chemotherapy or radiation therapy. This type of MDS is called secondary MDS .
Genetics. There are no known direct genetic risk factors associated with MDS. An increased risk of developing MDS is rarely inherited (passed from generation to generation in a family).
Symptoms and Signs : People with MDS may experience the following symptoms or signs. Sometimes, people with MDS do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not MDS. If you are concerned about a symptom or sign on this list, please talk with your doctor.
Easy bruising or bleeding
Shortness of breath
Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you’ve been experiencing the symptom(s) and how often.
Relieving the symptoms caused by MDS is an important part of your care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.
Diagnosis : Doctors use many tests to diagnose MDS. Some tests may also determine which treatments may be the most effective. Your doctor may consider these factors when choosing a diagnostic test:
Age and medical condition
Type of disease suspected
Severity of symptoms
Previous test results
In addition to a physical examination, the following tests may be used to diagnose MDS:
Blood tests. A complete blood count (CBC) test measures the numbers of red blood cells, white blood cells, and platelets.
Peripheral (circulating) blood smears. A drop of blood is placed on a slide, smeared into a thin film, and placed under a microscope for examination. The percentages of the different types of cells are counted, and cell morphology (the appearance of cells under the microscope) is looked at to find out if or how the cells are different from healthy cells.
Bone marrow biopsy and aspiration. These two procedures are similar and often done at the same time. Bone marrow has both a solid and liquid part. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. An aspiration removes a sample of fluid with a needle. The samples are then analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) to determine the percentage of red blood cells, white blood cells, platelets, and blasts. A common site for the bone marrow biopsy and aspiration is the pelvic bone, which is located in the lower back by the hip. The skin in that area is numbed with medication beforehand, and other types of anesthesia (medication to block the awareness of pain) may be used. The appearance of the bone marrow tissue, along with blood cell counts and chromosomal analysis (see below), is needed to confirm a diagnosis of MDS.
Cytogenetic (chromosomal) analysis. Looking at the chromosomes of the cells in the blood and bone marrow shows specific abnormalities that help doctors tell the difference between MDS and other blood disorders. About 50% of people with MDS have one or more chromosomal abnormalities, regardless of the subtype. Primary MDS often has one chromosomal abnormality. Secondary MDS often has many or complex chromosomal changes. The most common abnormalities affect chromosomes 5, 7, 8, 11, 12, and 20.
Immunophenotyping. Immunophenotyping is the examination of antigens, a specific type of protein, on the surface of the MDS cells. Immunophenotyping allows the doctor to confirm the exact type of MDS.
MDS is classified into several different subtypes, depending on blood cell counts, the percentage of blasts in the bone marrow, and the risk that it will turn into AML. Also, MDS is classified as either primary MDS or secondary MDS and may be given a disease staging called an IPSS score. These classifications help doctors plan treatment. Each is described below in more detail.
WHO system for MDS subtypes
The World Health Organization (WHO) developed a classification system for MDS to standardize the definitions of the different subtypes. The seven subtypes of MDS in this system include:
Refractory anemia (RA). The primary sign of RA is anemia. White blood cell counts and platelet counts are normal. There are less than 5% blasts found in the bone marrow. This subtype of MDS does not often turn into AML.
Refractory anemia with ringed sideroblasts (RARS). People with this subtype of MDS have anemia, similar to those with RA, except more than 15% of the red blood cells are sideroblasts. A sideroblast is a red blood cell in which the iron in the cell appears to be in a ring around the nucleus (the center of the cell where the genes are found). The white blood cell and platelet cell counts are usually normal. People diagnosed with RARS have a low risk of developing AML.
Refractory cytopenia with multilineage dysplasia (RCMD). In this subtype, people have less than 5% blasts and less than 15% ringed sideroblasts in the bone marrow. The other bone marrow cells look abnormal when viewed under the microscope. At least two of the blood cell counts are low. RCMD may eventually turn into AML.
Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). This subtype is similar to RARS, in which people have anemia and more than 15% sideroblasts. The other bone marrow cells also look abnormal when viewed under the microscope. In addition, at least two types of blood cell counts are low. RCMD-RS may eventually turn into AML.
Refractory anemia with excess blasts (RAEB). People with RAEB can have decreases in all or some of their blood cell counts. There are less than 5% blast cells in the blood and 5% to 20% blasts in the bone marrow. (People with more than 20% blasts in the bone marrow are diagnosed with AML.) People with RAEB may also have lower white blood cell and platelet counts. About 40% of people diagnosed with RAEB eventually develop AML.
Myelodysplastic syndrome, unclassified (MDS-U). People diagnosed with this subtype have decreased numbers of white blood cells, red blood cells, or platelets, but do not have the specific signs of the other MDS subtypes.
MDS associated with isolated del(5q). People with this subtype have anemia and fewer than 5% blasts, and genetic material is missing from chromosome 5.
CMML and JMML. In addition to the seven MDS subtypes above, chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) are types of blood cancers that the WHO classifies as “mixed myelodysplastic/myeloproliferative diseases”. Unlike other types of MDS in which blood counts are low, white blood cell counts are higher in these subtypes. Both CMML and JMML begin after a mutation (change) happens in a type of blood cell called a monocyte. CMML generally occurs in people ages 65 to 75, while JMML is most common in children younger than 6. Treatment is similar to MDS and can include chemotherapy and/or stem cell transplantation.
In addition to subtype, MDS is called either primary or secondary MDS. Primary MDS is much more common than secondary MDS. About 80% of people with MDS have primary MDS.
In primary MDS, no apparent risk factors can be found. This may also be called de novo MDS.
Secondary MDS occurs because of damage to the DNA from chemotherapy or radiation therapy previously given to treat another medical condition. MDS can develop two to 10 years after such treatment. Secondary MDS is often associated with more complex chromosomal abnormalities.
The International Prognostic Scoring System (IPSS) is another classification system used by doctors to help predict a person’s risk of developing AML and overall survival. The IPSS looks at factors such as the percentage of blasts found in the bone marrow, extent of chromosomal changes, and the degree of cytopenia (low blood cell counts).
Poor prognostic factors include:
Low numbers of more than one type of blood cell
More blasts in the bone marrow
Many chromosomal abnormalities
The total IPSS score places people with MDS into four distinct groups: low risk, intermediate risk-1, intermediate risk-2, and high risk. People with MDS who have a low IPSS score have the best outlook for survival and need less aggressive treatment. For patients with lower IPSS scores, overall survival rates tend to be lower when they need red blood cell transfusions (a procedure in which blood or blood cells are transferred from one person to another) compared to those who do not need transfusions. A person diagnosed with a high-risk subtype of MDS and whose IPSS score is high usually needs more intensive treatment.
Recurrent: Recurrent MDS is MDS that comes back after a period of remission (absence of symptoms; also called “no evidence of disease” or NED). If there is a recurrence, the subtype and IPSS score may need to be determined again using the systems above.
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