What are other Names for this Condition? (Also Known As/Synonyms)

• MDS (Myelodysplastic Syndromes)

What is Myelodysplastic Syndromes? (Definition/Background Information)

• Myelodysplastic Syndromes (MDS) are a group of conditions characterized by the disordered (dysplastic) development of all non-lymphocyte blood cells (called myeloid cells). MDS is caused by various abnormalities of the bone marrow
• Bone marrow is the spongy tissue found inside some of the bones. Typically, it is the primary site of blood cell production (hematopoiesis). The blood cells include:
  • Red blood cells (erythrocytes), which transport ‘gases’ such as oxygen
  • White blood cells (leukocytes), vital to the immune system
  • Megakaryocytes, which fragment to form platelets. Platelets clot blood and recruit collagen-producing cells (fibroblasts) to the scene of an injury
• These diverse cells develop from myeloid stem cells (blasts) inside the bone marrow. This process is mediated by different signals that steer the growth and division of the blasts down different pathways (lineages)
• The different blood cells can thus be considered “cousins” of each other. This is because they share a common ancestral stem cell, though they have diverged down separate lineages
• The presence of any abnormalities in the blasts or their signaling system may disrupt their development and cause Myelodysplastic Syndromes. Different forms of MDS are classified based on the cause or specific abnormalities produced

According to the 2016 World Health Organization (WHO) classification guidelines, the following six main types of Myelodysplastic Syndromes are identified:

• MDS with single lineage dysplasia (MDS-SLD)
• MDS with ring sideroblasts (MDS-RS) - which is further subdivided into MDS-RS-SLD and MDS-RS-MLD types
• MDS with multilineage dysplasia (MDS-MLD)
• MDS with excess blasts (MDS-EB) - which is further subdivided into MDS-EB-1 and MDS-EB-2 types
• MDS with isolated del(5q)
• MDS unclassifiable (MDS-U)

An additional provisional entity termed “refractory cytopenia of childhood” is also included in the 2016 WHO classification.

• Myelodysplastic Syndromes are more commonly diagnosed in older adults, with the average age of onset typically around 65 years. However, it can occur at any age. The risk factors for MDS include exposure to certain chemicals or radiation and prior treatment with chemotherapy or radiation therapy for other conditions
• The signs and symptoms of Myelodysplastic Syndromes may include fatigue and weakness, shortness of breath, frequent infections, easy bruising and bleeding, pale skin, and enlarged spleen
• MDS diagnosis involves blood tests, bone marrow biopsy, and cytogenetic analysis to identify genetic abnormalities. In case of delayed treatment, the complications may include anemia, infections, bleeding disorders, and progression to acute myeloid leukemia (AML)
• Treatment aims to alleviate symptoms, improve blood cell counts, and prevent progression to malignancies such as AML. Other treatment options for Myelodysplastic Syndromes include supportive care, blood transfusions, growth factors, and stem cell transplantation for eligible patients
• The prognosis of Myelodysplastic Syndromes varies widely depending on factors such as the severity of MDS, the specific genetic abnormalities present, and one’s response to treatment. Some individuals may have a relatively indolent course, while others may experience disease progression and complications

Who gets Myelodysplastic Syndromes? (Age and Sex Distribution)

• Myelodysplastic Syndromes (MDS) are rare conditions that are primarily observed in older adults, usually 60 years and older (median age at diagnosis is 65 years)
• According to medical literature:
  • The incidence of MDS in adults 80 years and above is 36 cases per 100,000 population
  • While the incidence of MDS in adults 60 years and below is 5 cases per 100,000 population
• Children and young adults are rarely affected
• Both males and females are affected, but a higher number of cases are reported in men
• Worldwide, individuals of all racial and ethnic groups may develop the condition

What are the Risk Factors for Myelodysplastic Syndromes? (Predisposing Factors)

The risk factors for Myelodysplastic Syndromes may include the following:

• Advancing age: Over 75% of MDS are reported in individuals over 60 years of age
• Smoking
• Exposure to radiation, including radiotherapy
• Exposure to certain industrial chemicals, such as benzene
• Exposure to fertilizers and pesticides
• Cancer therapy, including chemotherapy
• Exposure to certain heavy metals such as lead and mercury

It is important to note that having a risk factor does not mean one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Myelodysplastic Syndromes? (Etiology)

The exact cause of Myelodysplastic Syndromes (MDS) is not well-established.

• MDS constitutes a group of bone marrow disorders characterized by abnormal development and maturation of blood cells. In MDS, the bone marrow fails to produce enough healthy blood cells, resulting in dysfunctional cells
• MDS can affect red blood cells, white blood cells, and platelets. The abnormal cells often have a higher risk of transforming into acute leukemia
• It may develop due to a combination of genetic, environmental, and other factors. It is believed to involve genetic mutations in the bone marrow cells that regulate blood cell development

What are the Signs and Symptoms of Myelodysplastic Syndromes?

The signs and symptoms of Myelodysplastic Syndromes (MDS) may depend on the type and severity of the condition. It may vary widely from one individual to another. In general, the signs and symptoms of MDS may include:

• Malaise
• Easy bruising
• Tendency to bleed
• Bleeding from the gums
• Pale appearance (pallor)
• Fatigue
• Shortness of breath
• Tiny red rashes on skin (petechiae)
• Enlargement of spleen (splenomegaly)

How is Myelodysplastic Syndromes Diagnosed?

The following diagnostic tests and procedures may aid in detecting Myelodysplastic Syndromes:

• Physical examination and evaluation of medical history
• Complete blood count (CBC) test including WBC, platelet, and reticulocyte count
• Mean corpuscular volume (MCV) test
• Peripheral blood smear tests
• Erythropoietin blood test
• Protein electrophoresis
• Thyroid function test
• Bone marrow aspirate and biopsy to detect abnormal distribution of cells
• Cytogenetic analysis
• Flow cytometry
• Immunohistochemistry and immunophenotyping
• Fluorescence in situ hybridization (FISH) studies
• Radiological imaging studies
• Molecular genetic testing, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Myelodysplastic Syndromes?

The complications of Myelodysplastic Syndromes (MDS) may depend on the specific type of MDS. These may include:

• Anemia
• Severe and persistent infections
• Transformation of MDS to malignancies such as leukemias (blood cancer types)
• Excessive bleeding, especially during surgery
• Treatment side effects

How is Myelodysplastic Syndromes Treated?

The treatment of Myelodysplastic Syndromes (MDS) is based on the subtype of MDS and the age and health status of the individual. The treatment may be grouped into the following types:

• Supportive care: It addresses the symptoms and improves one’s quality of life. It may include:
  • Blood transfusion
  • Administration of erythropoiesis-stimulating agents (ESAs)
  • Administration of antibiotics in case of infections
• Therapy using medications: It can help slow the progression rate of the condition or prevent it from worsening. This may include:
  • Use of targeted molecular therapy drugs such as lenalidomide, azacytidine, and decitabine
  • Immunosuppressive therapy or biologic therapy
  • Low- or high-intensity chemotherapy
• Chemotherapy with stem cell transplant - it is considered for severe and aggressive MDS cases
• Clinical trials

Periodic monitoring or follow-up of the condition with the healthcare provider is essential and recommended.

How can Myelodysplastic Syndromes be Prevented?

Currently, no preventative guidelines or measures are available for Myelodysplastic Syndromes (MDS), as the exact cause of MDS is often unclear. However, an individual’s risk of developing the condition may be decreased by considering the following:

• Limiting exposure to the following:
  • Radiation
  • Industrial chemicals
  • Fertilizers and pesticides
• Quitting smoking
• Individuals, especially elderly adults, are urged to diagnose and treat any health conditions early and adequately

What is the Prognosis of Myelodysplastic Syndromes? (Outcomes/Resolutions)

The prognosis of individuals with Myelodysplastic Syndromes (MDS) depends on a set of factors that include:

• Specific MDS subtype
• Number and severity of cytopenias (low blood cell counts)
• Percent of blast cells in the bone marrow
• Type and number of chromosome changes

These factors help healthcare providers assign patients to specific risk groups based on a scoring pattern. Each factor is assigned specific numerical values, and the cumulative total (termed the risk score) determines whether a patient is a low-risk or high-risk candidate. This risk score gives information on how the specific type of MDS is progressing. The risk score also helps determine the treatment approach for a patient. Generally, individuals with a “low” risk score have an overall better prognosis than those with a “high” risk score.

The following three prognostic scoring systems are used for MDS by healthcare providers:

• International Prognostic Scoring System (IPSS)
• Revised International Prognostic Scoring System (IPSS-R)
• WHO classification-based Prognostic Scoring System (WPSS)

Nevertheless, regular medical follow-up is essential for monitoring and managing MDS effectively.

Additional and Relevant Useful Information for Myelodysplastic Syndromes:

Myelodysplastic Syndrome (MDS) was initially thought to be an early form of leukemia. It was even called “smoldering leukemia.” It is now known that MDS does not always progress to leukemia, so this term is outdated.