Myeloproliferative neoplasms (MPN)

In some MPNs, the bone marrow becomes scarred (fibrosis), reducing its ability to make blood cells. The spleen may compensate by producing blood cells. This leads to splenomegaly (enlarged spleen), causing:

• a feeling of fullness or discomfort in the upper left abdomen
• feeling full after small meals.

The liver may also enlarge (hepatomegaly). This can cause similar symptoms, but with discomfort on the upper right abdomen.

MPNs increase the risk of blood clots (thrombosis). These can block blood vessels and lead to serious events like stroke, heart attack, or deep vein thrombosis (DVT). MPNs can also cause abnormal bleeding, especially when platelets are very high or low.

Signs of DVT which is a clot in the leg or thigh, include:

• pain or swelling
• redness and warmth over the area.

Signs of Pulmonary Embolism (PE) which is when a clot travels to the lungs, include:

• sudden shortness of breath
• chest pain
• rapid heartbeat
• coughing up blood
• dizziness or light-headedness.

Seek urgent medical attention if you experience symptoms of a blood clot.

Most MPNs are driven by one of 3 mutations:

• JAK2 (most common)
• CALR
• MPL

These mutations affect how blood cells grow and divide.

• Age – the risk increases with age due to more frequent gene mutations or increase in the number of cells that carry the gene mutation over time.
• Environmental exposure – long-term exposure to high levels of benzene or ionising radiation may damage bone marrow cells.
• Family history – rarely MPNs may run in families (familial clustering), often involving shared or sometimes different gene mutations.
• Genetic conditions – mutations linked to haemochromatosis may raise the risk of developing polycythaemia vera (PV). This is still being studied.

Polycythaemia vera (PV) is the overproduction of red blood cells (causing high haematocrit and haemoglobin). Often white cells and platelets are also elevated.

Main risks include:

• blood clots
• stroke
• heart attack.

Symptoms may include:

• headaches
• dizziness
• fatigue
• itching (especially after showers)
• red skin (face, hands, feet)
• burning in the hands/feet/face
• blood clots
• abnormal bleeding
• high blood pressure
• abdominal discomfort (due to an enlarged spleen).

Possible progression:

• Can transform into post-PV myelofibrosis or rarely into acute myeloid leukaemia (AML)

Treatment includes:

• venesection (removing blood to reduce red cell count which reduces blood thickness)
• Blood-thinning medications
• cytoreductive therapy to reduce blood cell production

Essential thrombocythaemia (ET) is the overproduction of platelets in the bone marrow.

Main risks include:

• blood clots
• abnormal bleeding
• stroke.

Symptoms may include:

• fatigue
• headaches
• visual problems
• redness, tingling or burning in hands/feet/face
• blood clots (in lungs, legs, or abdomen)
• bleeding if platelet count is extremely high or low.

Possible progression:

• Can change into post-ET myelofibrosis or, rarely, AML.

Treatment includes:

• watch and wait
• blood-thinners
• cytoreductive therapy or immunomodulatory therapy to reduce platelet counts.

Primary myelofibrosis (PMF) is when scar tissue builds up in bone marrow, interfering with normal blood cell production.

World Health Organization (WHO) subtypes:

• early/prefibrotic PMF
• overt (fibrotic) PMF

Symptoms may include:

• fatigue
• weight loss
• night sweats
• fever
• enlarged spleen or liver
• anaemia
• bruising/bleeding
• bloods clots
• infections
• abdominal discomfort.

Potential progression:

• 10–20% may develop AML.

Treatment includes:

• JAK inhibitors and cytoreductive therapy
• transfusions
• splenectomy (rare)
• stem cell transplant (for eligible patients).

Sometimes people with essential thrombocythemia (ET) or polycythemia vera (PV) can develop myelofibrosis (MF) over time. This is called post-ET or post-PV myelofibrosis, treatment is the same as primary myelofibrosis (PMF).

Chronic myeloid leukaemia (CML) is an MPN caused by the Philadelphia chromosome (BCR-ABL gene fusion).

CNL is a rare MPN marked by the overproduction of neutrophils. It often progresses slowly but can become aggressive within 2 years.

Symptoms may include:

• fatigue
• night sweats
• bone pain
• weight loss
• easy bruising
• enlarged spleen/liver.

There is no standard therapy for CNL, and management is focused on symptoms. However, there is ongoing research into targeted treatments.

CEL is the overproduction of eosinophils (another type of white blood cell).

Symptoms depend on where eosinophils accumulate in the body and can include:

• fever
• cough
• fatigue
• muscle pain
• diarrhoea
• swelling around face/throat
• Itching.

Treatment options include:

• corticosteroids
• immunotherapy
• cytoreductive therapy
• targeted therapy
• chemotherapy (if progressed)
• stem cell transplant may be considered.

JMML is a rare MPN that affects young children, often under 4 years old. It is associated with genetic syndromes like Noonan syndrome or neurofibromatosis. Symptoms include an enlarged spleen and liver. Stem cell transplant is the main treatment with a curative aim.

MPN-NOS is an MPN that doesn’t fit clearly into another subtype. Symptoms vary depending on individual disease features.

Your treatment team will:

• review your past and current medical conditions
• ask about infections, clotting or bleeding issues
• record medications (prescription, over the counter, and supplements)
• perform a physical exam to check for signs of MPN.

A full blood count is a blood test that measures the number of red blood cells, white blood cells, and platelets in your blood. Abnormal counts may suggest an MPN.

These tests identify specific mutations or changes in your DNA that help classify the MPN and guide treatment:

• polymerase Chain Reaction (PCR) detects known gene mutations
• next Generation Sequencing (NGS) screens for multiple mutations at once (e.g., using an MPN gene panel)

Common gene mutations linked to MPN:

• JAK2 – found in most cases of PV and many cases of ET or MF. The JAK2 gene helps control how many blood cells your body makes. The JAK2 mutations involved in myeloproliferative neoplasms are the JAK2 V617F mutation (around 95% of PV patients have this) and the JAK2 exon 12 (about 2-5% of PV patients).
• CALR – associated with ET and MF
• MPL – mostly found in ET and MF

Knowing your gene mutation helps guide treatment and prognosis.

These tests help assess organ function and disease activity.

If MPN is suspected, a bone marrow biopsy may be done to:

• examine the structure and activity of your bone marrow
• check for fibrosis (scarring) or abnormal blood cell development
• help diagnose which type of MPN you have and to provide a baseline for monitoring. It is a key test to diagnose ET or MF.

Depending on your situation, you may need:

• imaging scans (e.g. ultrasound, CT) to assess spleen or liver size
• coagulation tests (blood test) if you have bleeding problems or very high platelets
• additional blood tests during diagnosis and treatment to track your progress over time

If you’re not experiencing symptoms or have low-risk disease you may not need immediate treatment. Instead, your doctor will monitor your health and blood counts through regular check-ups.

You may also be prescribed low-dose aspirin to help reduce clotting risks.

View our previous webinar that might provide more information relevant to your circumstance.

 

Watch & wait

These are the most commonly used treatments for MPN.

Aspirin

• Taken daily to reduce blood clot risk.
• Makes platelets less “sticky” but doesn’t lower their number.

Venesection (Phlebotomy)

• Blood is drawn (like donating) to reduce red blood cell count which reduces blood thickness.
• Usually used in polycythaemia vera (PV).

Cytoreductive therapy

• Used to reduce the number of blood cells produced.

Hydroxycarbamide (Hydroxyurea)

• Daily capsule.
• Possible side effects include allergy, anaemia, nausea, skin conditions (including increased risk of skin cancer), diarrhoea or constipation

Pegylated interferon

• Long-acting injection (weekly or often less frequently over time).
• Preferred in younger people or those planning pregnancy.
• Increasingly used in people of all ages.
• Possible side effects include flu-like symptoms, fatigue, appetite loss, depression, mood changes.

Anagrelide

• Lowers platelet count (mainly used in ET).
• Taken as a capsule.
• Not currently funded on the PBS (Australia).
• Possible side effects include cardiac – increased heart rate, shortness of breath.
• Must not be stopped suddenly.

These block abnormal signals that cause blood cells to grow too much. They’re often used in myelofibrosis and other high-risk MPNs.

Ruxolitinib

• Tablet taken daily.
• Helps reduce spleen size and symptoms.
• Possible side effects include anaemia, low platelets, headaches, dizziness, increased risk of skin cancers.

Momelotinib

• For myelofibrosis with anaemia.
• Possible side effects include low platelets, infections, nausea, diarrhoea, increased risk of skin cancers.

Imatinib

• Used in chronic eosinophilic leukaemia (CEL).
• Blocks faulty BCR-ABL1 gene signals.

Supportive care helps manage symptoms and side effects but doesn’t treat the cancer directly.

Transfusions include:

• red blood cell transfusions for anaemia and fatigue
• platelet transfusions for bleeding caused by low platelets.

Growth factors:

• encourage the bone marrow to make more blood cells
• are given as an injection under the skin
• may cause flu-like symptoms or bone pain.

Antibiotics:

• Are given when your white cells are low, you are at high risk of developing an infection.

Vaccines:

• are important to reduce infection risk
• are mostly given in the inactivated (non-live) form

Always check with your treatment team before having vaccinations, including live vaccines. These can be given in some cases.

Treatment affects people differently.

You may experience:

• anaemia (low red cells) – tiredness, breathlessness
• thrombocytopenia (low platelets) – easy bruising or bleeding
• neutropenia (low white cells) – higher risk of infection.

You’ll have regular blood tests to monitor your health.

A stem cell transplant is the only known potential cure for some types of MPN. However, it is only suitable for a small number of patients, generally younger people and with high-risk disease. Your haematologist will advise if this is right for you.

Surgical removal of the spleen may be considered if it’s very enlarged and causing problems. This is rare, as many people respond to JAK inhibitors that reduce spleen size.

Clinical trials test new treatments or combinations of treatments. You may be offered a place in a trial by your doctor. Trials can give access to promising therapies not yet available.

Participation is voluntary, and you can withdraw at any time.

You can search current clinical trials:

• Australian Cancer Trials
• ClinTrial Refer.