Myelodysplastic neoplasms (MDS)

• persistent tiredness and fatigue
• weakness
• shortness of breath with minimal exercise
• looking pale

• recurring infections, especially chest infections
• fevers
• sore mouth/mouth ulcers

• easy bruising
• purpura – a rash of small red dots (often on the lower limbs first) due to small capillary bleeds, known as petechiae
• bleeding from the nose and gums

Cause

Low red blood cells (RBC) or haemoglobin (Hb)

You might notice

Tiredness, weakness, pale skin, shortness of breath, heavy legs, difficulty concentrating, feeling lightheaded, rapid or irregular heartbeat.

Cause

Low white blood cells / neutrophils (WBC)

You might notice

More frequent or severe infections eg. chest or skin, fevers, shivering, chills, low blood pressure, mouth ulcers.

Cause

Low platelets

You might notice

Easy bruising and bleeding eg. nosebleed, cuts that keep bleeding, coughing up blood, petechiae – tiny unraised red blood spots under the skin, often starting in the legs.

Cause

All three blood cell types are low

You might notice

A mix of symptoms from all three conditions.

This classification sorts MDS dependent on the mutations or genetic abnormalities. These are found through cytogenetic tests which examine the structure of chromosomes (DNA) in your bone marrow cells.

MDS with low blasts and isolated 5q deletion (MDS-5q)

• Blasts: <5% bone marrow and <2% peripheral blood
• Cytogenetics: 5q deletion alone, or 1 other abnormality (other than monosomy 7 or 7q deletion)

MDS with low blasts and SF3B1 mutation (MDS-SF3B1)

• Cytogenetics: absence of 5q deletion, monosomy 7, or complex karyotype
• Mutations: SF3B1, detection of >15% ring sideroblasts may substitute for SF3B1 mutation

MDS with biallelic TP53 inactivation (MDS-biTP53)

• Blasts: <20% bone marrow and peripheral blood
• Cytogenetics: usually complex
• Mutations: 2 or more TP53 mutations, or 1 mutation with evidence of TP53 copy number loss or cnLOH

MDS with low blasts (MDS-LB)

• Blasts: <5% bone marrow and <2% peripheral blood

MDS, hypoplastic (MDS-h) – <25% age adjusted bone marrow cellularity

• Blasts: Not applicable

MDS with increased blasts (MDS-IB1)

• Blasts: 5-9% bone marrow or 2-4% peripheral blood

MDS with increased blasts (MDS-IB2)

• Blasts: 10-19% bone marrow or 5-19% peripheral blood or Auer rods

MDS with fibrosis

• Blasts: 5-19% bone marrow; 2-19% peripheral blood

The International Prognostic Scoring System – Molecular (IPSS-M) risk calculator for MDS predicts the risk of MDS transforming into an acute leukaemia or your likely prognosis. The potential risk of MDS transforming to AML and overall survival (life expectancy) is calculated into:

• Very low
• Low
• Moderate low
• Moderate high
• High
• Very high

Your treatment team will discuss your risk score and your treatment options.

Signs that the MDS is progressing (transforming) may include:

• frequent infections
• bleeding (e.g. from the nose or gums)
• bruising
• frequent blood transfusions

Watch and wait (active observation) involves regular monitoring. This includes blood tests and general health. No intervention is needed unless the person develops signs and symptoms the MDS it is progressing.

Supportive care controls symptoms of MDS and side effects. Supportive care aims to improve quality of life. It is frequently used for older people or those with other health problems. This group of people are often unable to tolerate the stronger treatments for MDS. Supportive care does not aim to treat the disease. It can help with symptoms such as shortness of breath, bruising or bleeding.

Supportive care therapies may include:

• Blood transfusions – many people with MDS have low haemoglobin and need regular red blood cell transfusion. This reduces symptoms like shortness of breath, dizziness and fatigue.
• Platelet transfusion – low platelets are a symptom of MDS. Symptoms of low platelets include bleeding and bruising easily. Having platelet transfusions reduces the risk of bleeding.
• Antibiotics – many people with MDS may have a low white cell count. This increases the risk of developing severe infection. Antibiotics can prevent a simple infection becoming life-threatening.
• Iron chelators – red blood cells contain iron. If blood transfusions are regular and ongoing, this increases iron levels (iron overload). This can be damaging to body organs. Iron chelators help remove excess iron from the body.

Targeted therapy directly targets the mutations/changes inside the blood cancer cells. It also slows down the growth or speeds up the rate at which the blood cancer cells die. For MDS it works in several ways:

• Immune system modulator – boosts the immune system to attack and destroy cancer cells
• Angiogenesis inhibitor – blocks the growth of blood vessels so cancer cells can’t grow and spread
• Cancer growth inhibitor – kills or stops the growth of cancer cells

Lenalidomide is an targeted therapy. It is a tablet usually taken once a day for 21 days and then one week off. It can be taken long term.

The goal of targeted therapy for MDS is to decrease the need for blood transfusions. One of the side effects of may be low blood cell counts which may require supportive care. Your doctor will discuss the best option available for you.

Common side effects:

• constipation and/or diarrhoea
• nausea
• fatigue
• cough
• feet and hand swelling
• body aches and pains
• headache
• stomach pain
• rash
• low blood counts
• risk of infection
• bleeding
• change of taste and smell

Chemotherapy (chemo) literally means therapy with chemicals. Chemo is also called cytotoxic because it kills cells. It especially kills cells that multiply quickly like cancer cells. Chemo is used in MDS to reduce the number of blast cells in your bone marrow. Then normal stem cells can make red blood cells, white blood cells and platelets.

There are a few types of chemo that treat MDS. It is either given orally, subcutaneously (needle under the skin) or intravenously (IV). The type of chemo you receive will depend on your type of MDS and your prognosis.

Low intensity chemo

Low intensity chemo may be given to people with intermediate II or high risk MDS.

Decitabine and cedazuridine is an oral chemo. It blocks the genes that help cancer cells grow and helps genes to produce normal cells. It is taken once a day for 5 days every month for six months.

Azacitidine is also a low intensity chemo. It works on the genes that affect how normal blood cells develop. It is a subcutaneous (under the skin) injection (needle). It is usually given in a clinic or outpatient ward, usually in the stomach or thigh. Each month the chemo injection is given either:

• 7 days in a row
• or five days in a row, then a 2-day weekend break, then the next two days

It may take up to six months to work and can be given long term.

The aim of low intensity chemo is to:

• improve MDS symptoms
• reducing the need for blood transfusion
• decrease the time spent at outpatient clinic appointments
• improve quality of life

High-intensity chemotherapy

People with MDS who have a high risk of progressing to leukaemia may have the same chemo as people with acute myeloid leukaemia (AML). High intensity chemo is higher doses of stronger medications that have stronger side effects. Sometimes it is called high-dose or induction chemo because its goal is to bring on (induce) remission. It is given in hospital intravenously (IV) over days or weeks because the side effects are more severe.

The goal of high-intensity chemo in MDS is complete remission. Remission means killing a large number of the unhealthy (dysplastic) cells from the bone marrow. This hopefully enables the bone marrow to work normally.

Chemotherapy side effects

Everyone gets different side effects with chemo. You may have no side effects, one or more, or they may change over time. There are medications and other ways to manage side effects. Your treatment team will monitor your side effects and advise how to help.

Common side effects:

• risk of infection
• nausea and vomiting
• change of taste and smell
• mucositis
• constipation and/or diarrhoea
• fatigue
• chemo brain (foggy brain)
• body aches and pains
• sun sensitivity
• rash
• peripheral neuropathy (high dose chemo)
• hair loss/thinning (high dose chemo)

A stem cell transplant (bone marrow transplant) is where your stem cells are replaced with new stem cells after high dose chemotherapy and/or radiotherapy. There are two types of stem cell transplants. Allogeneic stem cell transplant is used in MDS. A stem cell transplant may be used if the MDS gets worse or does not respond to treatment. This treatment is not available for everyone because there are very serious side effects, including a risk of dying.

Allogeneic (donor) stem cell transplant

The stem cells transplanted in an allogeneic transplant are from a donor. Usually, a brother or sister with the same tissue type as you. A blood test can see if they are the same tissue type, a HLA matched donor. The stem cells can also come from a volunteer donor who is not related but are a HLA match.

In an allogeneic stem cell transplant the donated stem cells create a new immune system. The new immune system destroys any blood cancer cells left after the high dose chemo. The healthy donated stem cells also rebuild your blood.

Common side effects:

• low blood counts
• all the same side effects as chemo, but more severe
• graft-versus-host disease (GvHD) – where the new immune system attacks normal cells.

These side effects can go on for years after the stem cell transplant.