Myelodysplastic syndromes (MDS)
What is MDS?
Myelodysplastic syndromes (MDS, or myelodysplasia) are a group of diseases which all affect, to a greater or lesser extent, the production of normal blood cells in the bone marrow. MDS occurs as a result of a mutation (or change) in one or more of the genes that control blood cell development. This change or changes results in the abnormal growth of blood stem cells.
The original mutation is preserved when the affected stem cell divides and produces a “clone”; that is, a group of identical cells all with the same defect. This is why MDS is sometimes described as a “clonal blood stem cell disorder”. Mutations in dividing cells occur all the time and cells have clever ways of stopping these abnormalities persisting and causing problems within the body. The longer we live, however, the more chance we have of acquiring mutations that manage to escape these safe-guards. That is why MDS, like most leukaemias and other cancers, becomes more common as we get older. This naturally occurring or spontaneously-arising MDS is referred to as primary MDS.
In MDS, abnormal bone marrow stem cells (called blast cells) produce increased numbers of immature blood cells. These cells do not grow properly and often die prematurely. This results in lower numbers of mature red blood cells, white blood cells and platelets being produced. The blood cells that do survive are often of poor quality, are abnormal in shape (dysplastic) and are unable to function properly. This means that people with MDS often have a very active bone marrow but a low number of circulating blood cells. Without enough red blood cells, white blood cells and platelets you can become fatigued, more susceptible to infections, and to bleeding and bruising more easily.
Which type of MDS do I have?
There are different types of MDS and the disease can vary in its severity and the degree to which normal blood cell production is affected. People with mild disease are often found to simply be anaemic, or they might have a lower than normal white blood cell or platelet count, but in many cases they have few, if any, troubling symptoms from their disease. In more severe cases, the lack of circulating blood cells is more pronounced, causing more symptoms.
The current World Health Organisation’s classification system recognises several major subtypes of MDS. These subtypes are distinguished from each other by the degree to which normal blood cell production is affected, the number of blast cells present and the likelihood of transformation into acute myeloid leukaemia. Knowing the exact type of MDS you have is important because it helps the doctor to decide on the best course of treatment to recommend for you.
Refractory anaemia (RA) – In this type of MDS, the red blood cells are most affected, causing anaemia. The bone marrow contains less than 5% abnormal blast cells and there are none found in the circulating blood. This type of MDS rarely transforms to leukaemia and treatment is regular observation or blood transfusion only.
Myelodysplastic syndrome with del (5q) chromosome – Red blood cells are affected, causing anaemia. There are usually less than 5% blast cells in the bone marrow and circulating blood and it is associated with a good prognosis.
Refractory anaemia with ringed sideroblasts (RARS) – Similar to RA, but in this case the red blood cells are unable to process the iron that normally goes into making haemoglobin, the oxygen-carrying component of the red cell. Instead the iron granules are deposited in a way that forms a ring around the nucleus of a developing red blood cell – this is called a ringed sideroblast.
Refractory anaemia with excess blasts – type 1 (RAEB-1) – One or more blood cell types are affected. The bone marrow contains between 5% and 9% blast cells and there are only a small number of blast cells (less than 5%) found in the circulating blood.
Refractory anaemia with excess blasts – type 2 (RAEB-2) – One or more blood cell types are affected, but this time the bone marrow contains between 10% and 19% blast cells and the number also increases (between 5% and 19%) in the circulating blood. There is a greater likelihood of transforming to acute myeloid leukaemia.
Refractory cytopenia with multilineage dysphasia (RCMD) – Two or more blood cell types are usually affected here but again the bone marrow contains less than 5% blast cells, and there are usually none found in the circulating blood.
Refractory cytopenia with multilineage dysphasia and ringed sideroblasts (RCMDRS) – Similar to RCMD, but with ringed sideroblasts found in the red blood cells.
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) – These are a group of diseases that have characteristics of both myelodysplastic (abnormal bone marrow cells producing too few blood cells) and myeloproliferative (abnormal bone marrow cells producing too many blood cells) neoplasms. These include chronic myelomonocytic leukaemia (CMML), juvenile myelomonocytic leukaemia (JMML), atypical chronic myeloid leukaemia (aCML) and myelodysplastic/myeloproliferative neoplasms unclassifiable (MDS/MPD-U).
How common is MDS?
Overall, MDS is relatively uncommon, with an incidence of between four to five per 100,000 of the population. However, in patients over the age of 60, this increases to anything from 20 to 50 per 100,000. It is therefore one of the more common haematological disorders in the elderly.
It’s difficult to be sure of the exact number of people who have MDS. This is because in many cases the disease develops slowly and people don’t have any symptoms for a long time.
Who gets MDS?
While MDS can occur at any age, the majority of cases (over 90%) develop over the age of 60. MDS can occur very occasionally in children.
What causes MDS?
Why defects arise in the bone marrow and cause MDS in a particular person at a particular time is difficult to understand, although the effects of ageing on cell growth appears to play a major role. Any process which damages genes and leads to mutations may have a role in the development of MDS. There are also some recognised factors that may put some people at a higher risk of developing MDS:
- ageing appears to be the most important risk factor for MDS because the risk of developing mutations increases with age
- exposure to high levels of some environmental chemicals, especially benzene and petroleum products
- exposure to chemicals in tobacco smoke
- people previously treated for cancer or other conditions with chemotherapy are at an increased risk of developing what is called secondary or treatment-related MDS. This accounts for less than 10% of all cases of MDS
- previous radiation therapy, or accidental exposure to high levels of environmental irradiation
- people with certain congenital disorders such as Bloom’s Syndrome, Down’s Syndrome, Fanconi anaemia and neurofibromatosis can have unstable genes and are more at risk of developing mutations that cause MDS or cancer.
What are the symptoms of MDS?
Many people in the early stages of MDS have no symptoms at all and it is picked up accidentally during a routine blood test. In other cases people go to see their General Practitioner because they are experiencing some troubling symptoms. The types of symptoms that people experience depend on how severe their disease is and the type of blood cell that is most affected.
The most common symptoms are caused by a lack of red cells, or anaemia:
- persistent tiredness and fatigue
- shortness of breath with minimal exercise
- looking pale.
Abnormal white cell function, often with low white cell counts, causes:
- recurring infections, especially chest infections
- sore mouth due to mouth ulcers.
Abnormal platelet function, often with low platelet counts, causes:
- easy bruising
- purpura – a rash of small red dots, seen often on the lower limbs initially, due to small superficial capillary bleeds which are known as petechiae
- tendency to bleed from the nose and gums.
Many people with MDS have a combination of symptoms. This is because the production of all of the blood cell types may be affected by the disease. Some of these symptoms may also be seen in other illnesses, including viral infections. It is important to see your doctor if you have any symptoms that do not go away so that you can be examined and treated properly.