Myelodysplastic syndromes (MDS), also known as myelodysplasia, are a group of blood disorders that result in immature red blood cells do not mature into healthy red blood cells. Bone marrow is the spongey, soft tissue found in the centre of most bones, and is primarily responsible for the production of blood cells in the body.
Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps remove waste from our bodies. There are three primary types of blood cells produced in bone marrow stem cells (immature blood cells). Red blood cells (RBCs), or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. White blood cells (WBCs) are responsible for fighting infection and disease in the body. Platelets are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after an injury. MDS causes bone marrow to produce red blood cells that don’t develop into healthy cells, which makes the body more susceptible to infection.
MDSs are generally more common in men, and are often diagnosed after 60 years of age. However, anyone can develop this disease.
Types of Myelodysplastic Syndromes
There are several types of MDSs, some of which may progress into other types of MDS or acute myeloid leukaemia if left untreated.
MDS with Single Lineage Dysplasia
MDS with single lineage dysplasia (MDS-SLD), also known as refractory cytopenia with unilineage dysplasia, are rare disorders characterised by significantly low levels of one type of blood cell (RBCs, WBCs, or platelets). MDS-SLD can have a good prognosis.
There are three subtypes of MDS-SLD.
Refractory Anaemia
Refractory anaemia is the subtype of MDS-SLD that is characterised by significantly low levels of red blood cells. This subtype can result in reduced oxygen flow throughout the body. Refractory anaemia is less aggressive than other forms of MDSs, and is classified as low risk.
Refractory Neutropenia
Refractory neutropenia is the subtype of MDS-SLD that is characterised by significantly low levels of white blood cells. This subtype may show minimal symptoms, except an increased susceptibility to infection. Refractory neutropenia is generally classified as low risk.
Refractory Thrombocytopenia
Refractory thrombocytopenia is the subtype of MDS-SLD that is characterised by significantly low levels of platelets.
MDS with Multilineage Dysplasia
MDS with multilineage dysplasia (MDS-MLD), also known as refractory cytopenia with multilineage dysplasia, are rare disorders characterised by significantly low levels of two or more types of blood cells (RBCs, WBCs, and platelets). They can occur in any combination of refractory anaemia, refractory neutropenia, and refractory thrombocytopenia, and is the most common type of MDS. MDS-MLD may not have as good of a prognosis as other types of MDS.
MDS with Ring Sideroblasts
MDS with ring sideroblasts (MDS-RS), also known as refractory anaemia with ring sideroblasts, is rare, and involves significantly low levels of red blood cells that have a ring of iron around the outer edge of the cell. This is caused by red blood cells being unable to process the iron used in the production of haemoglobin, causing it to build up in the cell. MDS-RS is further categorised into single lineage and multilineage dysplasia’s, with multilineage MDS-RS being more common.
MDS with Isolated Del(5q)
MDS with isolated del(5q) is a rare subtype of MDS that is characterised by a genetic mutation affecting chromosome five in patient DNA, or more specifically, a deletion of chromosome five. In most cases, this disease involves refractory anaemia, however it can also involve refractory neutropenia and refractory thrombocytopenia. MDS with isolated del(5q) is often non-aggressive, and can have a good prognosis.
MDS with Excess Blasts
MDS with excess blasts (MDS-EB) is a rare subtype of MDS categorised by the presence of excess blast cells, which are immature cells. They are characterised by significantly low levels of one or more types of blood cell (RBCs, WBCs, or platelets), occurring as refractory anaemia, refractory neutropenia, and refractory thrombocytopenia. MDS-EB may not have as good of a prognosis as other types of MDS.
There are two types of MDS-EB, based on the percentage of excess blasts present in the bone marrow and/or blood. Type one MDS-EB (MDS-EB1) is generally less severe, and occurs when blasts make up 5-9% in bone marrow, and less than 5% in the blood. Type two MDS-EB (MDS-EB2) is generally more severe, and occurs when blasts make up 10-19%, and between 5-19% in the blood.
MDS Unclassifiable
MDS unclassifiable (MDS-U) is a rare subtype that does not fit into any other category of MDS. The number of blasts in the bone marrow and the blood are often normal, and may be caused by genetic mutations.
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are a group of blood cancers that have characteristics of both MDS and MPN. Symptoms and treatments will vary based on the patient’s cancer characteristics.
Treatment
If cancer is detected, it is generally staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.
MDS is not staged and graded like most cancers, as the outlook for these cancers are not based on tumour size or metastasis. Instead, scoring systems have been created to assess the outlook of these cancers based on other factors.
Revised International Prognostic Scoring System (IPSS-R)
The revised international prognostic scoring system (IPSS-R) is based on five factors:
- The percentage of blasts in bone marrow.
- The type and number of chromosome abnormalities in the cells.
- The level of RBCs (measured as haemoglobin) in the patient’s blood.
- The level of neutrophils (a type of WBC) in the patient’s blood.
Factors are given a score from 0 (very good) to 4 (very poor), and added up to be placed in a risk group:
- Very low risk.
- Low risk.
- Intermediate risk.
- High risk.
- Very high risk.
The score given helps to assess a person’s prognosis, as well as potential treatment options.
WHO Prognostic Scoring System (WPSS)
The world health organisation (WHO) prognostic scoring system (WPSS) is based on three factors:
- The type of MDS based on the WHO classification.
- Chromosome abnormalities (grouped as good, intermediate, or poor).
- Whether or not the patient needs regular blood transfusions.
Factors are given a score from 0 (very good) to 4 (very poor), and added up to be placed in a risk group:
- Very low risk.
- Low risk.
- Intermediate risk.
- High risk.
- Very high risk.
The score given helps to assess a person’s prognosis, as well as potential treatment options.
Treatment Options
Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you. Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for MDS may include:
- Watch and wait.
- Chemotherapy.
- Stem cell transplants.
- Blood transfusions (to help control symptoms).
- Bone marrow transplants.
- Drug therapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
While the cause of MDS remain unknown, the following factors may increase the likelihood of developing the disease:
- Age.
- Genetic mutations.
- Exposure to certain chemicals, potentially including:
- Environmental chemicals.
- Benzene.
- Petroleum products.
- People who have had previous chemotherapy treatment.
- People who have had radiation therapy.
- People with certain congenital disorders, potentially including:
- Having a family history of MDS.
- Having a history of smoking.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Some patients with a MDS will appear asymptomatic in the early stages of disease. As symptoms progress, some of the following symptoms may appear.
- Anaemia, with symptoms potentially including:
- Fatigue.
- Dizziness.
- Weakness.
- Shortness of breath.
- Paleness.
- Neutropenia, with symptoms potentially including:
- Recurrent infections.
- Fevers.
- Mouth ulcers.
- Thrombocytopenia, with symptoms potentially including:
- Easy bruising.
- Purpura or petechiae (a rash of small red dots due to small superficial capillary bleeds).
- Bleeding of the nose and/or the gums.
- Weight loss/loss of appetite.
- Fever.
- Bone pain.
Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a MDS, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Blood tests
Blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Full blood count, which measures the levels of red blood cells, white blood cells and platelets.
- Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
- Blood smears to check changes in the number, type, shape, and size of blood cells for too much iron in RBCs.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-rays, ultrasounds, bone scans and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis.
Bone Marrow Aspiration & Biopsy
This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for abnormalities.
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells. This can be done by a fine needle aspiration (FNA), a core needle biopsy (CNB), or a trephine biopsy (removal of a small portion of bone for analysis).
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage MDS have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.