Blood cells are used in the body for many different and important functions, such as carrying oxygen (red blood cells), fighting infection (white blood cells), and controlling bleeding (platelets). Blood cells are formed and stored in the bone marrow, which is the spongy tissue inside large bones. Stem cells, or immature blood cells, are stored in the bone marrow and have the ability to develop into all three types of mature blood cells. When the body needs a specific type of blood cell, the bone marrow uses its stockpile of stem cells to produce the kind of mature cells needed for that particular situation.

In patients who have MDS, blood cells fail to mature normally. In other words, the bone marrow is unable to develop a normal amount of mature blood cells, and is also not able to increase blood cell production when mature cells are needed. Sometimes, even the cells that are produced do not function normally. The marrow eventually becomes filled with the immature cells and there is not room for the normal cells to grow and develop. MDS therefore causes a shortage of functional blood cells.

MDS is divided into five different subtypes that are classified according to the number and appearance of blast cells in the bone marrow. It is important for doctors to know the type of MDS a patient has, because each subtype affects patients differently and requires specific treatment. The International Prognostic Scoring System (IPSS) can help the doctor to determine the best treatment for an individual patient. The subtypes are as follows:

• Refractory anemia (RA). Bone marrow with less than 5% blast cells and abnormal red blood cell blasts
• Refractory anemia with ring sideroblasts (RARS). Bone marrow with less than 5% blasts and characteristic abnormalities in red blood cells
• Refractory anemia with excess blasts (RAEB). Bone marrow with 5-20% blast cells, and higher risk of changing into acute leukemia over time
• Refractory anemia with excess blasts in transformation (RAEBT). Bone marrow with 21-30% blast cells. This form is most likely to change into acute leukemia.
• Chronic myelomonocytic leukemia (CMMoL). Marrow with 5-20% blasts and excess monocytes (a specific type of white blood cell).

Approximately 15,000 new cases are diagnosed annually in the United States. The average age at diagnosis is 70. The most common types are RA and RARS. It is rare to have MDS before age 50. MDS is slightly more common in males than in females.

There is no clear cause for the majority of MDS cases, which is referred to as primary or de novo myelodysplastic syndrome. In some cases, however, MDS results from earlier cancer treatments such as radiation and/or chemotherapy. This type of MDS is called secondary or treatment related MDS, is often seen 3 to 7 years after the exposure, and usually occurs in younger people.

Other possible causative agents for MDS include exposure to radiation, cigarette smoke or toxic chemicals such as benzene. Children with pre-existing chromosomal abnormalities such as Down syndrome have a higher risk of developing MDS. MDS does not appear to run in families, nor can it be spread to other individuals.

MDS symptoms are related to the type of blood cells that the body is lacking. The earliest symptoms are usually due to anemia, which results from a shortage of mature red blood cells. Anemia causes patients to feel tired and out of breath because there is a lack of cells transporting oxygen throughout the body. MDS may also lead to a shortage of white blood cells resulting in an increased likelihood of infections. Another symptom of MDS is increased bleeding (e.g. blood in stool, nose bleeds, increased bruises or bleeding gums) which is due to low level of platelets. These symptoms can occur in any combination, depending on a given patient's specific subtype of MDS.

People who have MDS usually visit their primary care doctor first, with symptoms of fatigue, and are then referred to a hematologist (a physician who specializes in diseases of the blood). The diagnosis of MDS requires a complete analysis of the patient's blood and bone marrow, which is done by the hematologist. A complete blood count (CBC) is done to determine the number of each blood cell type within the sample. Low numbers of red blood cells, white blood cells, and or platelets are signs that a patient has MDS. Numerous other medical problems such as bleeding, nutritional deficiencies, or adverse reaction to a medication can also cause low blood counts. The hematologist will investigate other causes for low blood counts before assigning a diagnosis of MDS. Blood cells in patients with MDS can also be abnormal when viewed under the microscope.

A bone marrow biopsy is required to confirm the diagnosis of MDS and determine the correct MDS subtype. This procedure involves a needle used to take a sample of marrow from inside the bone. The area of the skin where the needle is inserted is numbed and sometimes the patient is also sedated. Patients may experience some discomfort but the procedure is safe and is over fairly quickly. Marrow samples are usually taken from the back of the hip bone (iliac crest). A sample of the marrow, known as an aspirate, and a small piece of bone are both removed with the needle.

A hematologist or a pathologist (a specialist in diagnosing diseases through cell examination) will carefully examine the bone marrow sample through a microscope. Microscopic examination allows the doctor to determine the number and type of blast cells (immature cells) within the marrow in order to identify the MDS subtype. Cells from the bone marrow are also sent for cytogenetic testing, which analyzes the cells' chromosomes. Forty to seventy percent of MDS patients have abnormal bone marrow chromosomes as a result of the disease. The pattern of these abnormalities can be used to predict how a patient will respond to a particular treatment. Thus, the full set of information provided by a bone marrow biopsy and CBC will ultimately allow the doctor to recommend the most effective treatment plan.

Once a diagnosis of MDS is established, the doctor will calculate the IPSS score for each individual patient. The bone marrow blast percentage, chromosomal abnormalities and number of different blood types that are reduced determine the score. A score of 0 to 3.5 is assigned to each patient. Patients with lower score have a better prognosis and usually should not undertake treatment upon initial diagnosis. Patients with a higher score have more aggressive disease and should consider more aggressive treatment.

Treatment for MDS is tailored to the patient's age, general health, specific MDS subtype, and IPSS score. Treatment varies for each patient, but most treatment strategies are designed to control the symptoms of MDS. This approach is called supportive care and aims to improve the patient's quality of life.

Supportive care for the MDS patients commonly includes red blood cell transfusions to relieve symptoms related to anemia. Red cell transfusions are relatively safe and the physician will review risks and benefits with this approach. Transfusions of any type only last a certain amount of time and therefore need to be repeated at certain intervals. Platelet transfusions can also be a way to control excessive bleeding. The doctor will decide with each individual patient when it is appropriate to give a transfusion. Antibiotics are used when needed to combat infections that can occur more frequently in patients with low white blood cell counts.

Bone marrow transplantation (BMT) is a type of treatment that attempts to provide MDS patients with a cure. This strategy requires the patients to be in fairly good health and are therefore more likely to be used in younger patients. Bone marrow transplantation (BMT) has been found to be a successful treatment for MDS patients under the age of 50 (and some over 50 in good health). Following BMT, many patients are able to achieve long-term, disease-free survival. Unfortunately, most MDS patients cannot receive a traditional bone marrow transplant because of older age or because they do not have a suitable donor. Bone marrow donors are usually siblings or are obtained from the national bone marrow registry. "Mini"-bone marrow transplants use less intense chemotherapy, and are currently being tested in older patients who would otherwise not be candidates for traditional bone marrow transplants.

Chemotherapy has been used to treat some MDS patients; however, the disease often recurs after a period of time. This type of therapy uses cell-killing drugs that may also damage healthy cells in the body. Most chemotherapy drugs are associated with some side effects. For these reasons, chemotherapy is generally not used until the MDS becomes more aggressive or the patient has a high IPSS score.

Growth factors are natural proteins that the body normally uses to control blood production. These substances stimulate the patient's bone marrow to produce healthy blood cells. Growth factors that stimulate white cell production are G-CSF (also called neupogen or filgrastim) and GMCSF (Leukine, sargramostim). In order to increase red cell production another growth factor, erythropoietin (Procrit) is used. These growth factors are safe with few side effects and are available only in the injectable form. The physician will decide if this treatment is appropriate for an individual patient.

There are no alternative therapies that have been proven to successfully treat MDS. Some of the available alternative drugs can have adverse side effects and therefore a physician should be informed if they are being used.

The prognosis for MDS patients depends on the subtype of their disease and the IPSS score. Patients with RA, RARS or low IPSS score rarely develop leukemia and may live with disease for some years. The higher-risk patients including those with RAEB, RAEBt, CMMoL or high IPSS scores progress more rapidly, and require intensive therapy to control the disease.

Managing MDS requires frequent doctor appointments to monitor disease progression and to evaluate the response to treatment. Fortunately for many patients, recent advances in therapy have significantly enhanced their ability to cope with MDS. Experimental drugs and a better understanding of the disease are likely to improve the overall prognosis in the future.

MDS is usually impossible to prevent. Being careful about daily activities and avoiding the use of aspirin-like products that thin the blood may prevent secondary complications of MDS such as bruising and bleeding. Practicing good hygiene and avoiding crowds or people with infections can sometimes prevent infections. A well balanced diet is recommended to increase overall energy.