Patient Education: Myelodysplastic syndrome (MDS)
by Mackenzie Gignac
Myelodysplastic syndrome (MDS) can be a tricky blood disease to explain. Dr. Shuh Tan, haematologist at St. Vincent’s hospital, is an expert in her field and specialises in treating MDS.
Dr. Tan helped guide us through the basics of understanding the diagnosis, what can be expected with treatment, and what research is currently being done on MDS to further our understanding and treatment options.
What is MDS?
MDS is a condition where the bone marrow does not produce enough healthy blood cells. It is a form of blood cancer caused by genetic damage in the primitive cells (stem cells) in the bone marrow.
Dr. Tan says that people with MDS have an active bone marrow. However, the blood cells that are made are defective and do not survive for very long, resulting in low blood counts in the circulation.
Patients with MDS often have anaemia (low red blood cells). Additionally, they can also have neutropenia (low white blood cells) and/or thrombocytopenia (low platelets).
In those with advanced MDS, the blood cells also do not fully mature. The bone marrow accumulates immature blood cells called blasts, and when this exceeds 20 percent, it is called acute leukaemia (AML). Overall, approximately 1-out-of-3 people with MDS will progress to AML.
There are many subtypes of MDS and can broadly be divided into two groups:
1. Low risk/ Early MDS
2. High risk/ Advanced MDS
What is the bone marrow?
Dr. Tan gives us some explanation about the function of the bone marrow. ‘The bone marrow is the ‘factory’ of blood cells, producing around 7 billion blood cells per hour,’ says Dr. Tan.
She says that the bone marrow contains stem cells that can be mature into any type of blood cells. Each blood cell lives for a certain amount of time, and is removed by the body as it gets old and damaged. The bone marrow in turn replenishes and releases fresh blood cells into the circulation.
There are three main types of blood cells:
- Red blood cells that carry oxygen to muscles and tissues
- White blood cells that help fight against infection
- Platelets that help stops bleeding
What causes MDS?
MDS is invariably caused by genetic damage to the stem cells in the bone marrow, called somatic mutations. Dr. Tan describes this as a change in the ‘programming of the factory.’
She says that the exact cause of this is not entirely clear. However, in recent years, advances in research have shown that aging plays a role in the genetic changes and development of this condition.
This might explain why MDS is more common in older people, mostly affecting those over 60 years old.
The other risk factors for developing MDS include:
- Prior chemotherapy or radiotherapy treatment
- Chronic exposure to petrochemicals
- Some rare congenital conditions
Is MDS curable?
Dr. Tan says that stem cells or bone marrow transplant using donor cells is the only potential for cure. However, this is a high-risk treatment that is only suitable to younger patients.
As most people with MDS are older, there is currently no known cure for the vast majority.
How will MDS affect my life?
The symptoms of MDS vary depending on which bloodlines are affected and the severity of the MDS.
Tiredness or fatigue is the most common symptom, especially in those with anaemia. Anaemia can also cause shortness of breath, dizziness, and reduced exercise capacity. Additionally, patients with low white blood cell counts are more vulnerable to infections. In those with low platelets, they may experience easy bruising and bleeding problems.
Some patients will also require regular hospital admissions for transfusions, or may be hospitalised due to severe infection.
Will my MDS require chemotherapy treatment?
Patients with early MDS may not require any treatment, and can be closely monitored.
In patients with significantly low blood counts, supportive care is one of the key focus in the management of this condition. This is aimed at improving symptoms through:
- Blood transfusions
- Platelet transfusions
- Growth factor injections
Chemotherapy or disease modifying therapy options may be available for patients with advanced MDS. Some of these options include:
Azacitdine or Vidaza is given as an injection under the skin for seven days every month.
Dr. Tan says that this drug can slow down or stop the condition from getting worse. In some cases, it may also improve blood counts and reduce the need for transfusions. The treatment is effective in about 40-to-50 percent of patients and can be continued for as long as it is working.
Lenalidomide or Revlimid is a tablet treatment used specifically for patients with 5q-syndrome subtype of MDS.
- Traditional chemotherapy is not often used since Azacitidine has become available. It is generally reserved for patients with very advanced MDS (MDS with excess blasts-2) or where MDS has transformed to AML.
Are there any other treatment options besides chemotherapy?
Dr. Tan advises that there are no other treatments available through the pharmaceutical benefit scheme (PBS) in Australia. Several new treatments are being developed for MDS, and these may be available through clinical trials. Some of these include:
- Targeted therapy - in patients with specific genetic changes
- Immunotherapy - that harnesses patients’ immune system to tackle the MDS cells
- Small molecule inhibitors - that can direct the killing of MDS cells
These new approaches are smarter ways to treat the disease. ‘They tackle the genetic changes that drive the disease, and disarm the machinery that help MDS cells survive,’ says Dr. Tan.
Through many years of research, there have been significant advances in understanding of MDS, notably the unravelling of the genetic complexity of this condition. ‘The complexity of MDS is why traditional chemotherapy has not been as effective,’ says Dr. Tan.
As the MDS & AML lead at St. Vincent’s Hospital,, what have been some of your key findings or major breakthroughs as an academic researcher?
Dr. Tan has a keen interest in MDS and AML. ‘I am drawn to the genetic changes that underpin these conditions. They are similar, but MDS is far more complex,’ says Dr. Tan.
Dr. Tan says she focused on MDS for her PhD research. She delved into how genetic mutation changes composition of stem cells in the bone marrow to result in MDS. Using this knowledge, she was able to curate models of MDS.
‘I generated lab models of MDS and used these to screen tens of thousands of drug compounds to discover potential new drugs to treat MDS.’ She hopes that this will eventually be of benefit, although it will take many more years before any of the newly discovered drugs can be tested on patients.
She also leads MDS and AML clinical trials at St. Vincent’s Hospital in Melbourne. ‘We have clinical trials which allow patients earlier access to some of the new treatments available,’ says Dr. Tan. She is passionate about expanding clinical trials options for all patients, including making these treatment options more accessible for patients in rural areas. ‘I am inspired to improve treatment options and the outcome of patients living with MDS & AML.’