What are Myelodysplastic Syndromes (MDS)?

Myelodysplastic syndromes are a group of blood cancers that develop from immature blood cells in the bone marrow. Blood stem cells are immature cells that normally develop into different types of blood cells, such as red blood cells (RBCs), white blood cells (WBCs), or platelets. In someone with a specific myelodysplastic syndrome (MDS), these immature cells can turn cancerous. The cancerous cells are called blasts, and they can cause a change in the functioning of healthy red blood cells, white blood cells, or platelets.

What are the different types of myelodysplastic syndromes (MDS)?

The different forms of MDS are diagnosed based on the specific changes that occur to the bone marrow and the blood cells. There is no standard staging system for MDS. The classification of the types of MDS is from the World Health Organization (WHO) and include:

• Refractory cytopenia with unilineage dysplasia (RCUD) - RCUD makes up about 5-10% of all MDS and is characterized by low numbers of one type of blood cell but normal counts of the other two blood cells. Examples of RCUD are refractory anemia (low red blood cells, which is the most common RCUD), refractory neutropenia (low white blood cells), and refractory thrombocytopenia (low platelets).
• Refractory anemia with ringed sideroblasts (RARS) - RARS accounts for about 10-15% of all MDS and is characterized by low red blood cells and 15% or more of the early red blood cells located in the bone marrow have iron deposit rings around the nucleus (ringed sideroblasts), which can be seen under a microscope.
• Refractory cytopenia with multilineage dysplasia (RCMD) - RCMD accounts for approximately 40% of all MDS and is characterized by lowered counts of at least two types of blood cells and those types of cells look abnormal when seen under a microscope.
• Refractory anemia with excess blasts-1 (RAEB-1) - In RAEB-1, one or more types of blood cell are low and look abnormal in the bone marrow, and blast cells are increased but are less than 10% of the cells in the bone marrow.
• Refractory anemia with excess blasts-2 (RAEB-2) - In RAEB-2, the blast cells make up 10-20% of the cells in the bone marrow, and the blood also contains more blasts (between 5% and 19% of the white blood cells).
• Myelodysplastic syndrome, unclassified (MDS-U) - MDS-U is a rare form of MDS in which the numbers of any one of the blood cells (RBCs, WBCs, or platelets) may be low in the blood, but less than 10% of the same type of cell look abnormal in the bone marrow. In addition, the number of blasts in the bone marrow is less than 5%, and the cells in the bone marrow contain at least one chromosomal abnormality.
• Myelodysplastic syndrome associated with isolated del(5q) chromosomal abnormality - In MDS with isolated del(5q), part of chromosome 5 is missing in the bone marrow cells, typically RBCs are low, WBCs are normal, and platelets may be higher than normal. In the bone marrow, the number of blasts is less than 5%.^1,2

Approximately one-third of people who have MDS may have their disease progress to acute myeloid leukemia (AML), a rapidly growing blood cancer.³

What causes myelodysplastic syndromes?

MDS occurs when there is a change to the DNA of the stem cells. This change, or mutation, may be the result of an inherited predisposition (passed from parent to child), or it may occur as a result of being exposed to something in the environment (like chemicals or radiation). Spontaneous DNA mutations can also occur during normal cell growth.^4,5

Each time any cell in the body divides, it makes a new copy of its DNA. Sometimes errors occur during this replication. These errors can cause the cell to develop abnormally and may lead to the development of cancer through the activation of oncogenes or the suppression of tumor suppressor genes. Oncogenes are genes that control how cells grow, multiply, and stay alive. Tumor suppressor genes are normally a stop mechanism that cause damaged cells to die or slow cell growth. When tumor suppressor genes are turned off, cancer cells can replicate more easily.⁵

Who gets myelodysplastic syndromes?

The number of new cases of MDS per year is not fully known. Some research has shown that there are about 10,000 new cases of MDS each year in the U.S, while other research has shown higher numbers.⁷ The incidence of MDS increases with age, with most cases being diagnosed in people in their 70s. It is rare to have MDS occur before age 40. MDS occurs more often in men than women.⁶

What factors increase a person's risk of developing myelodysplastic syndromes?

Risk factors that have been identified as potentially increasing an individual's chances of developing multiple myeloma include:

• Previous treatment with chemotherapy or radiation therapy
• Exposure to chemicals like tobacco smoke, pesticides, or benzene (found in cigarette smoke, many cleaning products, detergents, art supplies, paint strippers, and glue)
• Exposure to heavy metals like mercury or lead
• Family history of MDS
• Increasing age
• Genetic syndromes like Fanconi anemia, Shwachman-Diamond syndrome, Diamond Blackfan anemia, familial platelet disorder, and severe congenital neutropenia^1,6

What are the common symptoms of myelodysplastic syndromes?

In their early stages, MDS may not cause symptoms and may be discovered on a routine blood test. When MDS does cause symptoms, the symptoms are generally related to the lowered number of healthy blood cells:

• Anemia can result in symptoms of fatigue, dizziness, cold hands or feet, or pale skin.
• Neutropenia can result in repeated infections, or infections that won't go away.
• Thrombocytopenia can cause the body to bleed more easily, including frequent nosebleeds, bruising, or small, pinhead-sized red spots on the skin called petechiae.^1,8

What is the prognosis for myelodysplastic syndromes?

The prognosis, or expected outcome, for MDS varies by the subtype, how many blood cell types are affected, certain chromosomal abnormalities, the number of blast cells in the bone marrow, and the general age and health of the individual. In some people, MDS may be considered indolent. That is, it causes little or no symptoms. Other people may have more aggressive disease.¹