September 13, 2013 
Myeloblasts with Auer rods seen in Acute Myeloid Leukemia (AML).
Myelodysplastic syndrome are disorders of the myeloid blood cells made by stem cells or progenitor cells in bone marrow.
What Causes Myelodysplastic Syndrome?
The bone marrow produces abnormal blood cells leading to less functional myeloid cells. This causes severe anaemia requiring frequent blood transfusion. As the disease progresses the bone marrow can fail. In one third of MDS cases, the disease transforms into a very aggressive form of blood cancer – acute myelogenous leukaemia (AML).
MDS presents as a range of disease with variable prognosis for survival.
Estimating patient outcome depends on the International Prognostic Scoring System and risk is divided into low, in
Abnormal bone marrow cells in MDS
termediate and high risk – on a scale of 1-3. Three determinants are assessed including the proportion of blast cells in the marrow, normality of the genes in the marrow cells, and if the patient has one or more low blood cell counts. Each indicator is rated according to its severity and the ratings are combined into a score.
The IPR score determines the patients require more aggressive therapy such as a bone marrow transplant and best timing of therapy.
Risk Factors for MDS
The major risk factor for MDS is a previous course of chemotherapy treatment for cancer. If chemotherapy was given in combination with radiation therapy then the risk is even greater. Patients who undergo bone marrow transplants also get chemotherapy, so they are also at increased risk. Only a few patients who get chemotherapy go on to develop MDS, and it is important to put this in perspective.
Some genetic syndromes affect the functioning of the bone marrow and increase the risk of MDS. This might explain why in some families MDS occurs more often than expected.
Being a smoker increases the risk of MDS as some toxins in tobacco smoke impair functioning of the marrow. Exposure to large doses of radiation or benzenes and certain chemicals used in the oil industry increase the risk of developing MDS.
MDS is more a disease of the elderly and is more common in men than women.
Treatment of MDS
A number of therapeutic options are used to improve overall survival. The aims are to improve survivals and prevent progression to AML, to control the patients symptoms and to improve quality of life.
Blood transfusions and growth factors – such as erythropoeitin – are the most common treatments to counteract anaemia.
For low risk MDS, treatment with erythropoietin is often successful. If you have low erythropoietin and have had only a few transfusions, then it is likely a patient will respond well to erythropoietin. Immunosuppressive treatment with anti-thymocyte globulin plus cyclosporin A is an alternative or additional therapy.
Hypomethylating agents (eg azocytidine) are used to prevent the transformation into AML and help decrease the number of blood transfusions required.
Stem cell therapy offers a potential cure, but it is not suitable for all patients. It is more successful in younger patients and those with lower IPR scores. In recent times, more patients over 65 are getting this treatment option
Iron overload is a major complication in those who undergo repeated blood transfusions. Treating this increased iron burden helps keep iron levels stable. Chronic iron overload damages the liver and heart, and impairs hormone function. Measuring serum ferritin will help monitor iron levels and patients should be checked for signs of iron toxicity related organ damage.
Treatment with iron chelators – intravenous deferoxamine or oral deferasirox – will alleviate iron overload. Prior iron chelation therapy will improve survivals of patients who undergo stem cell transplantation.
Managing MDS Patients
MDS management of patients at the interface between MDS and acute myelogenous anaemia is difficult.
In the future, those who get treated for cancer will be profiled into low risk and high risk for MDS. Those at higher risk of MDS – smokers – will be given chemotherapy that is unlikely to trigger MDS. New medicines and improvements in stem cell treatments are also likely in the future to reduce MDS risk.
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