It is estimated that each year, about 5 new MDS cases are diagnosed per 100,000 persons. It predominantly occurs in older adults aged over 65, and the incidence increases with age. Men are more commonly affected.

MDS can occur as either a primary or a secondary disease. Primary MDS occurs with no known preceding factors and triggers. Although the mechanism by which primary MDS develops is unknown, it is believed to occur due to one or more acquired mutations in bone marrow cells that drive the cancerous changes associated with MDS. Over 100 genes have been identified that are frequently mutated in the bone marrow of the vast majority of individuals affected by MDS. Some of the most common genes associated with MDS are SF3B1, TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, TP53, and EZH2. Many of these genes are involved in the processes that control cell proliferation and death. 

MDS can also develop secondary to a preceding factor. For example chemotherapy for the treatment of other cancers, especially other forms of blood cancer, is known to increase the risk of developing MDS. In affected individuals, MDS typically appears 7-10 years after exposure to certain chemotherapy agents. Long-term exposure to environmental radiation and toxins such as petroleum products, pesticides, fertilizers, and benzenes can also contribute to the development of MDS. MDS can be passed on from parents to children in very rare cases. However, certain genetic conditions affecting the bone marrow such as Fanconi anemia, a rare and inherited blood disorder that results in bone marrow failure, can also increase the risk of developing MDS.

Many individuals affected by MDS may not experience symptoms for long periods of time. Symptoms typically progress slowly over time. Symptoms of MDS depend on the cell type affected. Affected individuals may only experience symptoms associated with one of the cell types or they may experience symptoms associated with two or all three. 

If red blood cells are low in number, the person is said to have anemia. Symptoms associated with anemia are fatigue and low energy, shortness of breath, heart palpitations, and skin paleness. The severity of symptoms depends on the severity of anemia and may vary from no symptoms at all to mild fatigue, to more severe symptoms. Anemia is the most common presentation in MDS.

If white blood cells are affected, the individual may experience recurrent infections affecting the skin, sinuses which cause nasal congestion or runny nose, lungs which cause coughs or shortness of breath, and the urinary tract which causes painful and frequent urination. A fever may also develop.

If platelets are affected, symptoms include easy bruising and bleeding. Affected individuals may notice larger than normal numbers of bruises or bruising in atypical body parts. They may also notice that they bleed for a longer period of time after small cuts and scrapes. Nosebleeds or bleeding from the gums may occur more frequently. In females, heavier than normal menstrual bleeding is possible. 

Additionally, spleen enlargement may occur, causing individuals to feel full soon after eating as the spleen pushes on the stomach. The spleen is an organ that removes old, injured, or abnormal blood cells. Because MDS causes the production of abnormal blood cells, the spleen experiences an increased workload, causing it to increase in size.

MDS is usually suspected when one or more blood cell types are found to have reduced numbers on a blood test. Particularly, if low blood cell numbers persist over time and despite treatment. Red blood cells are usually the first cell types affected. White blood cells and platelets may be reduced in number at the time of suspicion or follow later in the course of MDS. The physician may ask questions about associated symptoms, prior exposure to chemotherapeutic agents, occupational radiation and toxins, etc. They may also perform a physical exam to check for an enlarged spleen. Other tests are usually performed to confirm the diagnosis. 

A complete blood count (CBC) is usually the first test in the diagnosis of MDS. For a CBC, a blood sample is drawn and used to quantify the number of each cell type, as well as a few other characteristics that are helpful in the diagnosis process. In MDS, a CBC usually indicates low red blood cells and possibly low white blood cells and low platelets. In addition to a CBC, a specialist will look at the individual’s blood under a microscope to check whether blood cells have an abnormal appearance. Additionally, individuals may be required to undergo a bone marrow biopsy. This is a procedure in which a needle is used to remove a piece of the bone marrow. The bone marrow sample acquired can then be used to study the appearance of the developing blood cells in the bone marrow, genetic tests, and other studies. 

Genetic testing is particularly important as certain genetic abnormalities respond better to certain treatments or have a better or worse prognosis. Therefore, understanding the genetic profile of MDS cells guides management decisions. 

The goal of MDS is to reduce the severity of symptoms, slow or prevent progression into acute myeloid leukemia, and improve quality of life. MDS is often stratified into different risk categories based on the presence or absence of certain risk factors such as age, certain genetic aberrations, and the severity by which different blood cells are affected. Risk stratification guides treatment selection for individuals affected by MDS.

Individuals who do not experience any symptoms may not require any treatments and might only be monitored for disease progression.

Regardless of risk stratification, all affected individuals who experience symptoms receive supportive treatment in some form. Supportive blood transfusions can alleviate symptoms associated with low blood cells. However, frequent blood transfusions may increase the risk of iron overload, a condition in which high concentrations of iron lead to the deposition of iron in different organs, causing organ damage. Thus, some individuals may benefit from iron-chelating agents which are drugs that circulate in the blood, bind to excess iron, and prevent it from depositing in body tissues. Additionally, drugs known as growth factors induce an increased production of blood cells in the bone marrow which may decrease the frequency of blood transfusions, and thus, the risk of iron overload. Under certain circumstances, the use of antibiotics may be warranted to prevent infections in individuals with low white blood cells. 

Low-risk individuals may also be given hypomethylating agents. These are drugs that are believed to reverse the DNA alterations (i.e. methylation) that reduce the function of certain genes that work to inhibit tumor growth. 

Lenalidomide is a drug that is particularly effective in MDS with a specific genetic abnormality: the loss of a part of the long arm of chromosome number 5. Lenalidomide works by inducing tumor cell death, inhibiting new blood vessel formation that supports the growth of cancer cells, and modifying the immune system to attack cancer cells. Lenalidomide can lead to a noticeable improvement in a few months and often allow individuals to become transfusion-independent.

High-risk individuals may receive chemotherapy or a stem cell transplant in addition to supportive treatments. Chemotherapy refers to numerous agents that are toxic to cancer cells. A stem cell transplant is currently the only treatment option for MDS that can cure the disease. It is an invasive, surgical procedure in which the blood cell producing cells in the bone marrow of a healthy donor is collected to replace the abnormal cells in the bone marrow of the affected individual. Although potentially curative, a stem cell transplant is an invasive, high-risk procedure associated with a risk of death or significant complications. Thus, individuals are selected for a stem cell transplant based on strict criteria. Usually, only younger, healthy individuals with high-risk MDS qualify for this procedure.

The prognosis of MDS depends on many factors such as the individual's age, specific genetic abnormalities present, response to treatment, and the severity by which different blood cell types are affected. Based on these factors, MDS may be characterized as high-risk, intermediate-risk, or low-risk. Survival can range from months to years depending on the risk associated with an individual’s MDS. For example, MDS with deletion of the long arm of chromosome 5 (5q deletion) responds well to a drug called lenalidomide and has a much better prognosis than MDS with genetic abnormalities in chromosome 7. In addition, about one-third of MDS cases will eventually develop into AML. These individuals tend to have a poor prognosis. Secondary MDS is more likely to develop into AML than primary MDS.

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