Myelodysplastic Syndrome (MDS): Types, Causes, Diagnosis & Treatment

Blood is the essential nectar that every organ in the body needs to keep performing its function, which means that any disruption in the production of blood is bound to spell grave concern for affected individuals and their loved ones. Myelodysplastic syndrome is one such group of disorders. In this article, we unravel this condition, covering what it means, its types, diagnosis, treatment options, and other useful bits of information, with an aim to empower readers to better deal with this concerning condition. Let’s begin. 

What is Myelodysplastic Syndrome?

Myelodysplastic syndrome (MDS) is a condition characterised by abnormal development and functioning of blood-forming cells (blood stem cells). It leads to insufficient and defective production of blood cells, causing various health issues, such as cytopenias, which includes: 

• Anaemia (low count of red blood cells)
• Neutropenia (low count of neutrophils, a type of white blood cell)
• Thrombocytopenia(low platelet count)

In addition to the aforementioned, there could also be a potential progression to acute myeloid leukaemia (AML). 

What are the Types of Myelodysplastic Syndrome?

Myelodysplastic syndrome comprises several subtypes, each characterised by specific features. The classification is primarily based on the type and percentage of abnormal cells in the bone marrow, the presence of cytogenetic abnormalities, and the degree of cytopenias (low blood cell counts). The World Health Organization (WHO) classification system categorises MDS into six subtypes:

1. Refractory Cytopenia with Unilineage Dysplasia (RCUD)

The classic feature of RCUD is the presence of dysplasia, predominantly affecting one major blood cell lineage. For instance, if the erythroid lineage is primarily impacted, it may manifest as refractory anaemia with dysplastic changes in red blood cells.

2. Refractory Anaemia with Ring Sideroblasts (RARS)

Refractory Anaemia with Ring Sideroblasts (RARS) is another subtype of myelodysplastic syndrome. Individuals with RARS typically present with anaemia due to insufficient production of healthy red blood cells. 

3. Refractory Cytopenia with Multilineage Dysplasia (RCMD)

Individuals with RCMD typically present with low blood cell counts in multiple categories - red blood cells, white blood cells, and platelets. The disease course can vary, and there is a risk of progression to more advanced stages of MDS or acute myeloid leukaemia (AML). 

4. Refractory Anaemia with Excess Blasts (RAEB)

In RAEB, the distinguishing feature is the presence of an increased number of blast cells, which are immature cells that typically develop into blood cells. RAEB is further categorised into two subtypes based on the percentage of blasts in the bone marrow:

• RAEB-1 (Refractory Anaemia with Excess Blasts-1): Characterised by 5-9% blasts in the bone marrow.
• RAEB-2 (Refractory Anaemia with Excess Blasts-2): Characterised by 10-19% blasts in the bone marrow.

5. MDS with Isolated del(5q)

MDS with isolated del(5q) represent a distinct subtype of myelodysplastic syndromes, characterised by the deletion of the long arm of chromosome 5 (del(5q)). Patients often exhibit symptoms such as anaemia, necessitating red blood cell transfusions. Notably, the prognosis for MDS with isolated del(5q) is relatively favourable compared to other MDS subtypes. 

6. Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

MDS/MPN represent a complex group of hematologic disorders that share features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). MDS/MPN include disorders such as chronic myelomonocytic leukaemia (CMML), atypical chronic myeloid leukaemia (aCML), and juvenile myelomonocytic leukaemia (JMML), among others. 

What are the Stages of Myelodysplastic Syndrome?

Unlike some cancers, myelodysplastic syndrome is not typically staged in the same way. Instead, MDS is often classified based on the severity of the disease and the risk of progression. The two main classification systems used are the International Prognostic Scoring System (IPSS) and the Revised International Prognostic Scoring System (IPSS-R). These systems take into account factors such as the percentage of blast cells in the bone marrow, the cytogenetic abnormalities, and the degree of cytopenias (low blood cell counts).

International Prognostic Scoring System (IPSS)

• Low-risk MDS: This includes patients with low-grade MDS and a relatively favourable prognosis.
• Intermediate-1 risk MDS: Patients with slightly higher-risk disease but still intermediate prognosis.
• Intermediate-2 risk MDS: Higher-risk MDS with a less favourable prognosis.
• High-risk MDS: This category includes patients with a high percentage of blast cells in the bone marrow and a poorer prognosis.

Revised International Prognostic Scoring System (IPSS-R)

The Revised International Prognostic Scoring System (IPSS-R) refines the original International Prognostic Scoring System (IPSS) by incorporating additional factors and providing a more detailed and accurate assessment of risk. The IPSS-R classifies MDS into the following risk categories:

• Very Low
• Low
• Intermediate
• High
• Very High

It's important to note that the IPSS-R is a valuable tool for guiding treatment decisions and providing prognostic information, but it is not the only factor considered in the management of MDS. Treatment plans are often individualised based on the patient's overall health, specific characteristics of the disease, and response to therapy. .

What are the Symptoms of Myelodysplastic Syndrome?

Myelodysplastic syndrome may result in a spectrum of symptoms. These symptoms, while varying in severity, collectively indicate issues in normal production and function of blood cells. Common symptoms of myelodysplastic syndrome include:

• Persistent fatigue: In cases wherein MDS leads to Anaemia (low count of oxygen-carrying red blood cells, there is a reduced oxygen delivery to tissues and organs, resulting in persistent tiredness and weakness.
• Shortness of breath: Reduced red blood cell count compromises the blood's oxygen-carrying capacity, resulting in shortness of breath, even after minimal exertion.
• Weakness: Generalised weakness is a consequence of the overall decrease in functional blood cells, affecting the body's ability to carry out daily activities and maintain energy levels.
• Uncontrolled bleeding: MDS-related thrombocytopenia (low platelet count), can result in prolonged bleeding even from minor injuries.
• Easy bruising: Low platelet counts make individuals more susceptible to bruising, where even minor injuries can result in visible discoloration under the skin.
• Gastrointestinal bleeding: In advanced cases, MDS may lead to bleeding within the gastrointestinal tract, presenting additional challenges and health risks.
• Frequent nosebleeds: MDS-related deficiencies in platelets, critical for blood clotting, can lead to frequent and spontaneous nosebleeds, highlighting the impact on mucosal integrity.
• Enlarged liver or spleen: While less common, MDS may cause the enlargement of vital organs like the liver or spleen, signalling a more advanced stage of the disease.
• Pale skin: Anaemia-induced paleness is a visible sign of insufficient red blood cells, further highlighting the impact of MDS on hematopoiesis and overall health.
• Dizziness or lightheadedness: Diminished red blood cell production compromises blood flow and oxygen supply to the brain, resulting in dizziness or lightheadedness.
• Frequent infections: Reduced white blood cell counts in MDS impair the immune system's ability to defend against infections.

What are the Causes and Risk Factors of Myelodysplastic Syndrome?

The exact cause of MDS is often unknown, and it can develop spontaneously without a clear triggering event. However, several risk factors and potential contributors have been identified. These include:

• Previous cancer treatment: Exposure to certain cancer treatments, such as chemotherapy and radiation therapy, increases the risk of developing MDS.
• Chemical exposure: Prolonged exposure to certain chemicals, such as benzene and certain pesticides, has been linked to an increased risk of MDS. 
• Bone marrow disorders: Certain pre-existing bone marrow disorders, such as aplastic anaemia or paroxysmal nocturnal hemoglobinuria (PNH), may increase the risk of developing MDS.
• Immune system dysfunction: Autoimmune diseases and conditions affecting the immune system may be associated with an increased risk of MDS.
• Smoking: Cigarette smoking has been identified as a potential risk factor for MDS, particularly in individuals with a history of heavy smoking.
• Genetic factors: While MDS is not typically an inherited disorder, certain genetic mutations can increase the risk. 
• Age: MDS is more common in older adults, and the risk increases with age. The majority of individuals diagnosed with MDS are over the age of 60.
• Infections: Some viral infections, such as the human immunodeficiency virus (HIV) and certain types of human herpesvirus, have been suggested as potential risk factors for MDS.

How is Myelodysplastic Syndrome Diagnosed?

The diagnosis of myelodysplastic syndrome involves a combination of clinical assessments, laboratory tests, and bone marrow examinations. Here are the key steps in the diagnostic process:

1. Medical history and clinical evaluation: A thorough medical history is obtained, including information about symptoms, past medical treatments (especially chemotherapy or radiation therapy), exposure to toxins, and family history. A physical examination is conducted to assess overall health and detect any signs of abnormal bleeding, infection, or enlarged spleen or liver.
2. Blood tests: Complete blood count (CBC) is performed to evaluate the number and types of blood cells present. In MDS, abnormalities such as low red blood cell, white blood cell, and platelet counts may be observed. Peripheral blood smear may be examined under a microscope to assess the morphology of blood cells.
3. Bone marrow aspiration and biopsy: A bone marrow aspiration and biopsy are crucial for confirming the diagnosis of MDS. This involves extracting a sample of bone marrow from the hip bone or another large bone.
4. Cytogenetic analysis: Chromosomal analysis (karyotyping) is performed on the bone marrow cells to identify any chromosomal abnormalities, such as deletions or translocations. This information is essential for determining the specific subtype of MDS and guiding treatment decisions.
5. Molecular testing: Molecular tests may be conducted to identify specific genetic mutations associated with MDS, such as mutations in genes like TP53, SF3B1, or TET2. These tests can provide additional prognostic information.
6. Flow cytometry: Flow cytometry may be used to analyse the immunophenotype of cells in the bone marrow. It helps identify abnormal cell populations, including immature or blast cells.
7. Imaging tests: Additional tests, such as imaging studies (CT scans, MRI), may be performed to assess the spleen, liver, or lymph nodes for any abnormalities.

Once the diagnostic process is complete, the healthcare team can determine the specific subtype of MDS, assess the severity of the condition, and develop an appropriate treatment plan. 

Can Myelodysplastic Syndrome be Cured?

Myelodysplastic syndrome is a chronic condition, and a complete cure is challenging to achieve for many individuals. The outcome and prognosis for MDS vary widely based on factors such as the specific subtype of MDS, the severity of the disease, and individual patient characteristics. That said, there are various treatment approaches aimed at managing MDS, improving symptoms, and potentially slowing down the progression of the disease.

How is Myelodysplastic Syndrome Treated?

The treatment of myelodysplastic syndrome depends on various factors, including the specific subtype of MDS, the severity of symptoms, the patient's overall health, and other individual considerations. Here are some common approaches to treating MDS:

• Blood transfusions: For individuals with severe anaemia, red blood cell transfusions may be administered to improve oxygen delivery to tissues.
• Platelet Transfusions: Platelet transfusions may be given to address low platelet counts and reduce the risk of bleeding.
• Growth factors: Agents such as erythropoietin or granulocyte-colony stimulating factor (G-CSF) may be used to stimulate the production of red or white blood cells.
• Hypomethylating agents: Azacitidine and decitabine are hypomethylating agents that can be effective in treating certain subtypes of MDS. They work by modifying the DNA of abnormal cells, potentially slowing disease progression.
• Immunomodulatory drugs: Lenalidomide, an immunomodulatory drug, is commonly used in the treatment of MDS with isolated del(5q). It can improve blood cell counts and reduce the need for transfusions.
• Chemotherapy: Chemotherapy may be considered for higher-risk MDS or cases where there is a risk of progression to AML. However, its use is generally limited due to potential side effects.
• Stem cell transplantation: Hematopoietic stem cell transplantation may be considered for eligible patients. It involves replacing the abnormal bone marrow with healthy stem cells from a donor.
• Targeted therapies: Emerging targeted therapies may be used in specific cases, especially when certain genetic mutations are present. For example, drugs targeting specific mutations like IDH1/2 or FLT3 may be considered.

Can Myelodysplastic Syndrome be Prevented?

While there are no known strategies for preventing myelodysplastic syndrome as its exact causes are not fully understood, there are some general health recommendations that may contribute to overall well-being and potentially reduce the risk:

• Avoiding exposure to toxins: Minimise exposure to known carcinogens and toxins, such as benzene and certain pesticides, which have been associated with an increased risk of MDS.
• Cancer prevention strategies: Adopt a healthy lifestyle that includes regular exercise, a balanced diet rich in fruits and vegetables, and avoiding tobacco products.
• Occupational safety: Individuals working in industries with potential exposure to harmful chemicals should follow safety guidelines and use protective equipment to minimise the risk of exposure.
• Healthy ageing: While MDS is more common in older adults, maintaining good health as you age may contribute to overall well-being and potentially reduce the risk of certain diseases.

In addition, iIf there is a family history of MDS or other hematologic disorders, genetic counselling may be considered to assess the risk and provide information about potential genetic factors. 

Final Words

If you or a loved one is facing concerns related to myelodysplastic syndrome (MDS), seeking guidance and care from experienced specialists is essential. That’s when you can count on Max Hospitals. Our team of skilled haematologists and oncologists leverages state-of-the-art diagnostic tools, advanced treatment modalities, and a patient-centred approach to address the unique needs of individuals with MDS, and offer the highest standards of medical care.