Initial stages of MDS may be characterized by macrocytic anemia with mild thrombocytopenia or neutropenia. Patient may present with fatigue and malaise, two features of anemia. When the levels of platelets fall, petechiae, ecchymoses, epistaxis and gum bleeding may result. With bacterial or fungal infections the patient may have fever, cough, dysuria or shock as clinical manifestations. Some patients may develop hemoptysis, hematuria or have blood in stools. Severe cases of anemia may manifest as tachycardia and congestive heart failure. Enlarged spleen is characteristic of chronic myelomonocytic leukemia. This may lead to rupture and intraabdominal bleeding. Neutropenia may lead to fever and infections including pneumonia and urinary tract infections.

Bone marrow studies and a complete blood count including differential and peripheral blood smear are the diagnostic tests used in MDS. Disease is staged for assessing prognosis and also for planning treatment modality. Peripheral blood smear may show single cytopenia in the early stages which may develop into dicytopenia or pancytopenia in the later stages. Dysplastic changes and hypercellular marrow can be noted in histologic tests. Anemia and neutropenia may be mild or severe. Granulocytes show morphological changes with absence of granules or presence of Dohle bodies. Platelet counts may be considerably decreased. Bone marrow changes include hypercellularity with dysplastic changes. Increased marrow fibrosis is also noted. Erythroid cell precursors show multinuclearity. Cytogenetic studies enable to work out the chromosomal changes. This is significant considering the fact that primary MDS patients have very high rate of chromosomal abnormalities.

Staging of MDS is based on the International Prognostic Scoring System (IPSS). Percentage of myeloblasts is the first prognostic factor and this is evident in bone marrow study. Presence of cytopenias is the next factor, followed by karyotype.

The main treatment strategy for MDS is supportive therapy, with transfusion of deficient cells, and treatment of infections. In patients with acute leukemia or increasing myeloblasts, chemotherapy is recommended. Combination of cytarabine and anthracycline gives a good response rate of 30 to 40%. Azacytidine and lenalidomide is also approved in the treatment of MDS.

Supportive therapy helps to replace cells that are undergoing cell death. RBC transfusion is suggested for patients with moderate to severe form of anemia. To avoid transfusion-induced iron overload, iron chelation therapy may be required in patients receiving multiple RBC transfusions. In thrombocytopenia, platelet transfusion is found to be beneficial. Antithrombolytic agents are effective in stopping skin and mucosal bleeding.

In late stages of MDS and also in patients with poor prognosis, bone marrow transplantation may be suggested. This is usually done in patients below 55 years of age when they have an available, matching donor. But as the condition is mostly seen in patients who are above 60 years, this procedure is limited.

MDS may progress very slowly in many patients. Cytopenia and other complications like hemorrhage and infection are the main cause of mortality. In some patients the disease may be more aggressive and develop into AML. Subgroups of MDS with less than 5% myeloblasts have a prolonged clinical course. It very rarely progresses to AML. As the amount of myeloblasts increase, clinical course becomes shorter in duration and mostly develop into acute leukemia [9]. A prognostic scoring system is available for MDS based on three major variables – karyotype, number of cytopenias, and percentage of bone marrow blasts [10]. 

Based on the cause of the disease, MDS is classified into primary or idiopathic, and secondary MDS. About 80% of the cases of MDS do not have a definite, underlying cause and are referred to as primary MDS. Secondary MDS develops after exposure to sources that damage chromosomes. Patients undergoing radiotherapy or chemotherapy have an increased chance of developing MDS 5 to 7 years after exposure due to chromosomal abnormalities. MDS may develop within 2 to 3 years after treatment with anthracyclines and etoposides. Insecticides, weedicides, and fungicides may also cause this syndrome [3]. Certain chemicals like benzene are also associated with the development of MDS. Some of the congenital platelet disorders may increase the risk of this syndrome. Certain viral infections, genetic constitution and treatment for autoimmune conditions may also trigger MDS or AML [4].

Cytogenetic testing shows that patients with MDS may have:

• Normal chromosomal structure
• Chromosomal abnormalities due to translocation 
• Complex karyotypes

About 30% of the patients with primary MDS have complex karyotypes. About half of the patients who develop secondary MDS after radio- or chemotherapy also show complex karyotypes. This complexity is a bad prognostic factor in the treatment of MDS or AML. Translocation abnormalities may result in oncogenes which play a very important role in the development of this syndrome. Advanced age and male gender are also common risk factors in this syndrome [5].

One of the studies shows that about 13,000 new cases of MDS are reported each year in the US. Prevalence of MDS is around 35,000 to 55,000 cases in US and is similar in different parts of Europe as well. The median onset of the syndrome is around 70 years, but the condition may also be found in children. About 86% of the patients are above 60 years of age. Incidence of the syndrome increases with age with the risk increasing approximately five fold between 60 to 80 years. MDS is more common among males than in females with male-to-female ratio of 4.5:2.7 [6]. As the population of elderly people increases, prevalence also shows an increase. The disease is more prevalent in white people when compared to other groups [7].

Development of MDS is a multistep process and includes changes in the hematopoietic stem cells, the bone marrow, and the interaction between the two. A number of theories are implicated in the pathogenesis of this syndrome:

• Cellular damage 
• Genetic alterations
• Changes in bone marrow
• Dysregulation of immune system
• Changes in cell cycle regulation

Cellular aging and environmental exposures are presumed to accumulate DNA damage. The genetic mutations resulting from the two lead to clonal expansion and then MDS. Prior treatment with chemo- or radiotherapy brings about genetic alterations that primarily include MLL gene. Increased apoptosis and decreased cellularity are two features in elderly people that predispose them to MDS. Genetic alterations result in loss of micro-RNA that contributes to clonal expansion and also thrombocytosis [8]. Inhibition of tumor suppressor genes may induce apoptosis while inhibiting angiogenesis.

Cell apoptosis causes cytopenia during the early stages of the syndrome. Further gene mutation may add on to the existing genetic alterations and leads to clonal development. In addition to the structural changes in the DNA, alterations in gene expression also lead to epigenetic modifications. Many genes involved in tumor suppression, cell death, cell growth, cell differentiation, and cell cycle control, are silenced by these modifications. These aberrant gene expressions are involved in development of MDS. Increased cytokine levels promote apoptosis, characteristic of early stages of MDS. Changes in cellular signaling pathways lead to abnormal differentiation and growth of cells. Immune dysregulation may result in increased T cells which launch an attack on hematopoietic stem cells.

As the exact cause of the syndrome is not known, there are no methods available to prevent the development of the disease. Quitting smoking may be helpful in reducing the risk of MDS as in the case of cardiac diseases. Avoiding dangerous chemicals is another method to reduce the risk of developing this syndrome. Those who have serious cancers may have to undergo chemo- or radiotherapy which might increase the risk of MDS at a later stage.

Myelodysplasia, or myelodysplastic syndrome (MDS), is a group of acquired clonal disorders characterized by dysmyelopoiesis and cytopenias [1]. Abnormal hematopoiesis may affect erythrocytes, granulocytes and megakaryocytes. Patients with this condition are at an increased risk of anemia, infection, and hemorrhage. This clonal disorder may progress to acute myelogenous leukemia (AML) in some patients.

About 75% of the patients with MDS are above 60 years, but it may develop in childhood also. MDS may also occur after exposure to chemotherapy or radiotherapy. As the disease may progress to AML, it is considered to be a premalignant condition. Clinical course of the disease is highly variable. In most of the cases, a clear etiological factor cannot be identified. Treatment is often individualized after assessment of prognosis [2].

Myeloplasia, also known as myelodysplastic syndrome (MDS), refers to a group of disorders that arise due to the damage in the cells of bone marrow. The affected bone marrow produces lower levels of different blood cells. Many of the cells produced by the bone marrow are abnormal and often undergo cell death sooner than normal. In some cases MDS may develop into an aggressive form of cancer called acute myeloid leukemia. MDS is of two types based on the cause of the condition. Primary MDS does not have a definitive cause for the syndrome while secondary MDS have a known cause. Secondary MDS is often treatment-related, particularly chemotherapy and radiotherapy used earlier for treating cancer. Around 13,000 new cases of MDS are reported each year and the number is increasing. MDS is associated with a number of risk factors like certain genetic conditions, exposure to certain chemicals, age, gender and radiation. It is more prevalent in people above 60 years and males are more predisposed to develop MDS when compared to females.

Anemia is one of the most common symptoms of MDS. Patients with this syndrome may present with fatigue, weakness and shortness of breath. They are susceptible to infections, bleeding and easy bruising. Blood cell tests and bone marrow tests are used to diagnose this syndrome. Difference in the number and structure of the different blood cells is indicative of MDS. Blasts produced by the bone marrow mature into normal blood cells. Blasts cells do not mature and presence of too many of blasts in the bone marrow is characteristic of MDS.

MDS is characterized by three factors – percentage of blasts, presence of abnormal chromosomes, and count of blood cells. Patients are categorized into four risk groups with high risk group with more serious disease. The main types of treatment used in this syndrome is supportive therapy and chemotherapy. Combination of cytarabine and anthracycline is used generally. Patients with mild to severe form of anemia is recommended blood cell transfusion. In patients with late stages of the disease, bone marrow transplantation may be suggested. This method is usually recommended for patients below 55 years and the procedure is limited if the patient’s age is above 60 years. There are no known preventive measures for the disease since the actual cause is not clearly defined. Controlling the risk factors is the most important way to control this syndrome. Avoiding exposure to dangerous chemicals and quitting smoking reduce the risk of developing MDS.

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