Myelodysplastic Syndrome

A group of hematological disorders form myelodysplastic syndrome (MDS) and they result from lack of proper production or function of a person’s myeloid blood cells. MDS emanates from a disorder affecting the stem cells within the bone marrow, which brings down the levels of cells that form blood. When there are reduced myeloid blood cells, it causes impairment in blood production or hematopoiesis. In MDS there is increased number of immature myeloblasts that cannot effectively make mature red blood cells. The main sign of myelodysplastic syndrome is anemia because there is reduced production of red blood cells.

Myelodysplastic syndrome may sometimes be called pre-leukemia and the reason for that is because about a third of individuals having MDS with time tend to suffer from acute myeloid leukemia. At time of diagnosis, many people are passed the age of 60 and only about 6 percent are below the age of 50. In myelodysplastic syndrome, an individual’s body releases a lot of immature bone marrow cells referred to as blasts. The abnormal blasts engulf the healthy mature cells needed by the body. While stem cell transplant may cure some cases of myelodysplastic syndrome, it is a risky procedure that may not be performed on every patient. The life expectancy in people having myelodysplastic syndrome varies depending on the type of MDS and whether it will end up becoming leukemia.

 

 

Causes of Myelodysplastic Syndrome

 

Some genes that appear to mutate before MDS cells form include ASXL1, TET2, DNMT3A, TP53, RUNX1, SRSF2, and SF3B1. Some people may inherit these gene changes from their parents, however, mostly the changes happen as a person lives. Researchers have established that gene mutations linked with inherited syndromes such as familial platelet disorder are also linked to the development of MDS. The particular changes leading to myelodysplastic syndrome occur in RUNX1 gene. This is the gene responsible for controlling how blood cells develop. When there are changes or mutations in the gene, it makes cells not mature as they should, something that increases an individual’s risk of having MDS.

Usually mutations in several different genes inside bone marrow cells are needed before a person develops MDS. Some of the mutations most often seen in MDS cells include those in the DNMT3A, TET2, ASXL1, TP53, RUNX1, SRSF2, and SF3B1 genes. Some of these gene changes can be inherited from a parent, but more often they happen during a person’s lifetime.

During a person’s lifetime, environmental exposures may also contribute to MDS by causing damage to the DNA material found within bone marrow cells. People who smoke tobacco for example, may have damage to genes or mutations of genes hence leading to MDS. At other times, the gene mutations leading to MDS can occur without any obvious reason or outside exposures and such changes happen randomly, sometimes inside the cells with no outside cause.

The ability of gene changes to occur inside cells over time may be able to explain why older people largely suffer from MDS. In myelodysplastic syndrome, the body of an individual is not able to synthesize sufficient healthy blood cells.

The known risk factors contributing to MDS include:

• Old age- being over 60 years
• Smoking or use of tobacco
• Having exposure to radiation for example, being present in an environment where there is nuclear reactors or atomic bomb
• Getting exposure to benzene or other chemicals used in petroleum and rubber production
• Suffering other disorders like acquired aplastic anemia, Fanconi anemia, familial platelet disorder, congenital neutropenia, and Shwachman-Diamond syndrome
• Having previously being exposed to chemotherapy or radiation and radiomimetic agents like busulfan, nitrosourea, and procarbazine

 

Symptoms

Myelodysplastic syndrome may not present with any symptoms particularly during the early days of the disorders. Having said that, it is important to understand the effects of the syndrome on various blood cells and how the warning signs come about. The symptoms and signs include:

• Unusual bleeding
• Constant tiredness – a common symptom seen in people with anemia, and it is caused when there is insufficient amounts of red blood cells
• Paleness
• Bruises or tiny red marks appearing under the individual’s skin
• Shortness of breath, especially when an individual is active or exercising

 

 Treatment of Myelodysplastic Syndrome

To determine the right treatment for myelodysplastic syndrome, a doctor will have to determine what type of the disorder you have and its severity. Sometimes, a ‘watch and wait’ approach is taken by the doctor. The doctor does regular check-ups to find out how the symptoms are progressing or if the blood count is up to par. At other times, a doctor may consider a low-intensity treatment that includes:

• Use of chemotherapy drugs, which may also be administered to help treat cases of leukemia
• Use of immunosuppressive therapy to help stop the individual’s immune system from waging war on healthy marrow cells. This helps rebuild the individual’s blood count.
• Growth factors or man-made hormones that stimulate the bone marrow to synthesize more blood cells
• Iron chelation, which is the process of getting rid of excess iron in blood using specific drugs like deferasirox (oral) and deferoxamine (IV)

 

If low intensity treatment doesn’t seem to improve the symptoms of myelodysplastic syndrome, a doctor may suggest a high intensity treatment that includes:

 Stem cell transplantation: This is the only treatment believed to cure MDS. When doing stem cell transplant, a doctor orders for numerous radiation and chemotherapy sessions to help destroy cells within the bone marrow. A donor provides stem cells from their blood or bone marrow. After the transplant, the new cells begin to make blood cells in the body.

 Use of combo therapy:  A doctor may apply different chemotherapy to help treat the disorder.

 

 

Myelodysplastic Syndrome Life Expectancy

   The life expectancy for Myelodysplastic Syndrome Life Expectancy depends on the type of MDS an individual has, how likely the condition can turn to leukemia and other factors. There are two types of scoring systems that are available, which a doctor makes use of to find out appropriate treatment methodologist. Of course, no one can predict actual survival rate of a person, with this condition.

The two scoring systems are

1. International Prognostic Scoring System – This calculates the life expectancy for Myelodysplastic Syndrome based on the how many blast cells in the bone marrow are leukemic. The score, also factored in by checking amount of low white blood cells counts and chromosomal changes in the bone marrow cells; gives a ‘risk rating’. The risk rating shows how much is the likelihood for MDS to turn into leukemia.  So, if the risk level is low, then the median survival rate is 5.7 years; if it is intermediate 1 and intermediate 2, it is 3.5 years and 1.2 years respectively; and if the risk level is high,  then the median survival rate is  5 months.
2. WHO Prognostic Scoring System – This is based on the type of MDS, blood transfusions needed and chromosomal abnormalities. In this case, if the risk level is very high, the life expectancy for Myelodysplastic Syndrome 9 months, if it is high, it is 2 years, if it is ‘intermediate’, it is 4 years and if it is low, it is 5.5 years. Also if the ‘risk level’ is very low, then the medial survival rate to base Myelodysplastic Syndrome life expectancy is 12 years.

One may not that the above figures are based on research done till 2004. With more advanced treatments over the course of time, there is scope to believe that the life expectancy has increased.