Myelodysplastic syndrome (MDS) is the name of a group of conditions that occur when the blood-forming cells in the bone marrow are damaged. This damage leads to low numbers of one or more type of blood cells.

Normal bone marrow

Bone marrow is found inside certain bones, including the skull, shoulder blades, ribs, pelvis, and spine. It is made up of blood-forming cells, fat cells, and supporting tissues that help the blood-forming cells grow. A small fraction of the blood-forming cells are a special type of cell known as stem cells. Stem cells are needed to make new cells. When a stem cell divides it makes 2 cells: one cell that stays a stem cell, and another cell that can keep changing and dividing to make blood cells. There are 3 types of blood cells: red blood cells, white blood cells, and platelets.

Red blood cells pick up oxygen in the lungs and carry it to the rest of the body. These cells also bring carbon dioxide back to the lungs. Having too few red blood cells is called anemia. It can make people feel tired and weak and look pale. Severe anemia can cause shortness of breath.

White blood cells (also known as leukocytes) are important in defending the body against infection. The 2 major types of white blood cells are lymphocytes and granulocytes.

Lymphocytes are immune cells that are found in the bone marrow, the blood, and in lymph nodes. They make the antibodies that help the body fight germs. They can also directly kill invading germs by producing toxic substances that damage the cells. Lymphocytes are not usually abnormal in MDS.

Granulocytes are a group of white blood cells that destroy bacteria. They are called granulocytes because they contain granules that can be seen under the microscope. These granules are made up of enzymes and other substances that can destroy germs that cause infections. In the bone marrow, granulocytes develop from young cells called myeloblasts. The most common type of granulocyte is the neutrophil; this cell is crucial in fighting bacteria. Other types of granulocytes are basophils, and eosinophils. When the number of neutrophils in the blood is low, it is called neutropenia. This can lead to severe infections.

Monocytes, another member of the granulocyte family, are also important in protecting the body against bacteria. The cells in the bone marrow that turn into monocytes are called monoblasts. Monocytes can leave the bloodstream to become macrophages in tissue. Macrophages can destroy germs by surrounding and digesting them. They are also important in helping lymphocytes recognize germs and begin producing antibodies to fight them.

Platelets are thought of as a type of blood cell, but they are actually small pieces of a cell. They start as a large cell in the bone marrow cell called the megakaryocyte. Pieces of this cell break off and enter the bloodstream as platelets. Platelets are needed for your blood to clot. They plug up damaged areas of blood vessels caused by cuts or bruises. A shortage of platelets, called thrombocytopenia, can result in abnormal bleeding or bruising.

Myelodysplastic syndrome

In MDS, the cells in the bone marrow have problems making blood cells. Many of the blood cells that are formed by the bone marrow cells are defective. The body destroys these abnormal blood cells, leaving the patient without enough normal blood cells and low blood counts.

In about one-third of patients, MDS can progress to a rapidly growing cancer of bone marrow cells called acute myeloid leukemia. Because most patients do not get leukemia, MDS was previously classified as a disease of low malignant potential. As doctors learned more about MDS, it began to be considered a form of cancer. The major reason is that MDS is a clonal disease, which means that there is a large population of abnormal cells that all came from a single, abnormal cell. These abnormal cells are exactly alike -- just like identical twins -- and they share abnormal growth properties. Clonal growth is typical of cancer.

In the past, MDS was referred to as pre-leukemia and smoldering leukemia. Since most MDS patients do not get leukemia, these terms are not accurate and are no longer used.

Our document, Acute Myeloid Leukemia, provides more information about the leukemia that develops in MDS patients.

Types of myelodysplastic syndrome

The original classification of myelodysplastic syndrome (MDS) was developed more than 20 years ago at an international conference attended mostly by doctors from France, the United States, and Great Britain. This system was known as the French-American-British (FAB) classification.

The system used today is the World Health Organization (WHO) classification. This system seems to be more helpful than the FAB classification in predicting prognosis (outlook). There are 8 categories of MDS in the WHO system:

• refractory anemia (RA)
• refractory anemia with ringed sideroblasts (RARS)
• refractory cytopenia with multilineage dysplasia (RCMD)
• refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)
• refractory anemia with excess blasts-1 (RAEB-1)
• refractory anemia with excess blasts-2 (RAEB-2)
• myelodysplastic syndrome, unclassified (MDS-U)
• myelodysplastic syndrome associated with isolated del(5q)

Most of these categories are determined by the appearance of the cells in the blood and the bone marrow. One category is defined by a certain chromosome change in the bone marrow cells. Because small differences in the way the cells look can can change the diagnosis, doctors may sometimes disagree on the exact MDS category for a patient's disease.

Chronic myelomonocytic leukemia (CMML) was considered a type of MDS in the FAB classification, but is not in the WHO classification. Information about CMML can be found in our document, Chronic Myelomonocytic Leukemia.

Refractory anemia

People with refractory anemia (RA) have low numbers of red blood cells (anemia), but have normal numbers of white blood cells and platelets. In the bone marrow, the only cells that look abnormal are the early cells that develop into red blood cells (this is called dysplasia). There is a normal number (less than 5%). of very early cells called blasts. About 5% to 10% of all MDS patients have refractory anemia. This type of MDS seldom, if ever, progresses to acute myeloid leukemia. Patients with this type can live a long time.

Refractory anemia with ringed sideroblasts (RARS)

This condition is similar to refractory anemia except that many of the early red blood cells in the bone marrow contain iron deposits arranged in a circle (these cells are called ringed sideroblasts). About 10% to 15% of all people with MDS have this type. This type rarely turns into leukemia, and the outcome for people with this type is generally the same as for those with refractory anemia.

Refractory cytopenia with multilineage dysplasia (RCMD)

In this condition, the counts of at least 2 types of blood cells are low. In the bone marrow, those same types of cells look abnormal under the microscope (dysplasia). The number of blasts in the bone marrow is less than 5%. About 25% of people with MDS have this type. It changes into leukemia in about 10% of patients. Having this type of MDS will shorten a person’s life. One estimate is that half of patients will die within 2 years of diagnosis.

Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)

This is like RCMD, but at least 15% of the cells in the bone marrow are ringed sideroblasts. This type occurs about 15% of the time in patients with MDS. The chance of developing leukemia is more than 10%. Having this type of MDS will shorten a person’s survival. One estimate is that half of the patients will die within 2 years of diagnosis.

Refractory anemia with excess blasts-1 (RAEB-1)

Any one of the cell types can be low in the blood and look abnormal in the bone marrow. The number of blasts in the bone marrow is increased; but is still less than 10%. The chance of RAEB-1 turning into acute myeloid leukemia is about 25%. This type of MDS has a poor outlook and most patients die within 2 years.

Refractory anemia with excess blasts-2 (RAEB-2)

This type of MDS is similar to RAEB-1 except the bone marrow contains more blasts -- between 10% and 20% of the bone marrow cells are blasts. Any one of the cell types can be low in the blood and look abnormal in the bone marrow. The chance of RAEB-2 turning into acute myeloid leukemia may be as high as 50%.

Myelodysplastic syndrome, unclassified (MDS-U)

This type of MDS is uncommon. For a case to be considered MDS-U, the findings in the blood and bone marrow can't fit any other type of MDS. In the blood, numbers of any one of the cell types may be low and in the bone marrow either the white or megakaryocyte cell series looks abnormal under the microscope. The number of blasts in the bone marrow is less than 5%. Because this type is so rare, it has not been studied well.

MDS associated with isolated del(5q)

In this type of MDS, when the chromosomes of the bone marrow are tested, the only abnormality seen is a missing part of chromosome number 5. In the blood, the red cell counts are low, but the white blood cell counts are normal. Often the platelet count is increased. The number of blasts in the bone marrow is less than 5%. For unknown reasons, patients with this type of MDS have a very good prognosis. They often live a long-time and rarely go on to develop leukemia.

Secondary MDS

Cases of MDS based can also be classified based on the underlying cause. If no cause can be identified, it is called primary MDS. It is called secondary MDS when the cause of the disease is known. Secondary MDS is often called treatment-related MDS, because the most common cause is prior cancer treatment. This is discussed further in the section, "What are the risk factors for myelodysplastic syndromes?" Identifying MDS as primary or secondary is important because the secondary type is much less likely to respond to treatment.