Myeloproliferative neoplasms (MPN)

Myeloproliferative neoplasms, also known as myeloproliferative disorders (MPDs) are a group of conditions that are closely related to leukaemia.

Our bodies normally produce billions of blood cells every day. This process occurs inside our bones, in the bone marrow, the spongy substance inside our bones. The bone marrow contains stem cells which grow and mature into all the blood cells that our bodies need: red blood cells, white blood cells and platelets. Each type of these types of cells has a specific job to do inside our bodies.

With a myeloproloferative disorder (MPD), excessive production of a cell’s precursor leads to an increased number of that type of mature cell and to a corresponding increase or decrease in the number of other blood cells, which may be inhibited and crowded out. These results in symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.

There are approximately 1,900 cases of MPNs diagnosed every year.

The three types of MPDs most frequently diagnosed are separate disorders which each affect blood cell levels in a different way. These three most frequently diagnosed types are:

Essential Thrombocythaemia

Essential thrombocythaemia (ET) is one of a group of diseases called the myeloproliferative neoplasms (MPNs). MPNs affect the way blood cells are produced in the body. Patients with ET have too many platelets in their blood. Platelets are small fragments of cells which are needed to form a blood clot. The high number of platelets causes people with ET to have a higher risk of blood clotting. People with ET can also have bleeding problems because their platelets do not always work well.

People generally develop ET as adults and most people who develop ET are diagnosed at age 60 or older. It is more common in women than men, with two women being diagnosed for every man, particularly in patients who are less than 60 years of age. However, it must be noted that 20% of patients are older than 40 years of age at diagnosis.

What causes ET?

 

There are many conditions, other than ET which can cause a raised platelet count, such as arthritis. Before diagnosing ET, doctors will rule out these other causes.

 

While the exact cause of ET is not known, research has found that approximately 55% of people who have ET have a mutation in a protein that regulates blood cell production. This protein is known as Janus Kinase 2 (JAK2) and the mutation itself is JAK2 V617F. This mutation arises during your lifetime and is not present at birth.

 

In addition, a mutation in a gene known as CALR is present in 15% to 30% of patients with ET, and the MPL mutation is seen in 4% to 8% of patients.

 

Some 10% to 20% of patients with ET do not express any of these three mutations. This is referred to as triple-negative.

 

It is also important to be aware that, although some families seem to develop the disease more readily than others, ET is usually not inherited nor passed on from parent to child. However, and this is less common, an increased likelihood of the gene mutating (which can then lead to developing ET) can be inherited and is called familial ET. It resembles non-familial ET both in terms of clinical symptoms and mutations.

 

Finally, some researchers believe MPNs may also be triggered by past exposure to ionising radiation (a type of radiation that has very high energy, like medical x-rays or nuclear fallout) or to some chemical substances such as benzene and toluene.

Signs and symptoms of ET

 

Many patients with ET do not have any symptoms when they are diagnosed. Typically, these patients are identified following abnormal results during a routine full blood test for something else. If symptoms do develop, they tend to do so over time.

 

If you have persistent symptoms of ET, make an appointment to see your GP. Common symptoms of ET include:

  • Fatigue
  • Night sweats
  • Headaches (this can also include migraines with visual disturbances)
  • Itching
  • Fever
  • Swollen spleen (located under the ribs on the left of the abdomen, this organ helps to rid the body of toxins, waste and other unwanted materials)
  • Bone pain
  • Weight loss
  • Dizziness or light headedness
  • Reddish or purple skin
  • Bleeding or clotting
  • Unexplained bruising

In patients with ET, the increased numbers of platelets and white blood cells can result in blood clots (thrombosis) in a vein or artery, or they may cause bleeding (haemorrhage). Blood clots or bleeding are a major complication of ET. There is a 1% to 3% risk of arterial or venous blood clots occurring in a patient per year; however, if the patient has a JAK2 mutation, this risk increases to 7.7%.

 

Diagnosis of ET

 

ET is often suspected if a routine blood test shows that a patient has a high platelet count, also called thrombocytosis.

 

To make a diagnosis of ET, the following criteria must be present:

  • A platelet count of 450×109/L or higher
  • A bone marrow biopsy showing an increase in the numbers of enlarged, mature megakaryocytes (cells in the bone marrow that produce platelets)
  • Not meeting the diagnosis for another MPN, such as PV or MF
  • The presence of a JAK2, CALR or MPL mutation

 

If none of the mutations are present, other causes of primary or secondary thrombocytosis as well as diagnoses of PV and MF must be excluded. Primary refers to a condition that is the root cause of the illness, whereas secondary refers to a condition that has developed as a result of another one.

 

ET is diagnosed using laboratory tests including:

  • Blood tests – Blood tests can identify an increase in blood cells and exclude other causes of a high cell count.
  • Gene mutation analysis – This is to identify any gene mutations you may have, particularly JAK2, CALR or MPL.
  • Bone marrow investigations – You may have either a bone marrow aspiration or both an aspiration and a bone marrow biopsy. This will be done to look for classic signs of ET. During a bone marrow aspiration, the doctor or nurse takes some bone marrow cells up into a syringe. A bone marrow biopsy is when they remove a one to two-centimetre core of bone marrow in one piece using a trephine (a surgical instrument with a cylindrical blade). The sample is then sent to the laboratory for testing.

 

Treatment of ET

 

Overview of treatment

 

Most treatments for ET are intended to manage your symptoms and prevent any associated problems from blood clots or bleeding in order to maintain your quality of life.

 

Treatments for ET are aimed at lowering the production of platelets and maintaining normal blood counts. This is called cytoreductive therapy. There are a number of medications which can achieve this.

 

Treatment according to risk factors

 

Treatment will be based on an assessment of your risk factors regarding blood clots and bleeding. While cytoreductive therapy is fundamental in treating ET, managing any potential blood clots or bleeding is equally important. Your medical team will give you all the information about the treatment which is best for you.

 

Low-dose aspirin and anticoagulants may be used to prevent any blood clots, especially if you have a history of developing blood clots.

 

Medications

 

Cytoreductive therapy

 

Cytoreductive therapy is important in enabling ET and its complications to be controlled. It is the only treatment significantly associated with reducing the occurrence of blood clots. In patients with ET, first-line treatment is hydroxycarbamide, with second-line treatment being anagrelide.

 

Hydroxycarbamide (also known as hydroxyurea)

 

This is the most commonly used chemotherapy drug to treat ET and is available as a tablet or capsule.

 

An early study of patients with high-risk ET confirmed that the percentage of patients receiving hydroxycarbamide had significantly less blood clots or bleeding (3.6%) compared with patients not receiving any treatment (24%). In recent controlled studies of patients with high-risk ET, neither anagrelide nor interferon alpha could be shown to be superior to hydroxycarbamide for reducing blood clots or bleeding.

 

Hydroxycarbamide can cause mild side effects such as:

  • Increased risk of infection
  • Bruising or mild bleeding
  • Anaemia (as it reduces all types of blood cells, including red blood cells)
  • Fatigue
  • Diarrhoea or constipation
  • Sore mouth
  • Changes to the skin, including ulceration and increased risk of developing skin cancer

 

Hydroxycarbamide may also affect fertility. If you are taking it, you will be advised not to get pregnant or father a child, as there may be a risk of harming the developing baby. It is advisable to use effective barrier contraception while taking the drug and also for a few months afterwards. If hydroxycarbamide is used either alone or in combination with other chemotherapy drugs over a long period of time, it may slightly increase the chance of the ET developing into AML.

 

Anagrelide

 

Taken as a capsule, anagrelide is a drug that prevents the maturation of platelets. It is used to counter the overproduction of platelets. It lowers the platelet count and has some effect on the red blood cells.

 

Anagrelide is approved for reducing elevated platelet counts in at-risk patients with ET who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy.

 

Side effects of anagrelide include:

  • Headaches
  • Diarrhoea
  • Palpitations
  • Fluid retention

 

Interferon alpha

 

Interferon alpha is a substance which occurs naturally in the body and reduces the rate at which blood cells, including platelets, are made in the bone marrow. It can be made into a medicine to be given as an injection under the skin to treat a wide range of conditions, including ET.

 

Side effects of interferon alpha include:

  • Flu-like symptoms
  • Headaches
  • Vision disturbances
  • Depression
  • Liver and thyroid disease

 

However, it does not increase the risk of secondary leukaemia and can be used in pregnancy.

 

Busulfan

 

Busulfan is usually given to patients who have side effects when taking hydroxycarbamide. It can be given as a tablet. Like hydroxycarbamide, busulfan affects the bone marrow directly and can lead to a fall in the blood cell counts. Its main side effects are nausea and low platelet counts.

 

Your haematologist can advise you if busulfan is suitable, and will monitor your progress carefully during your treatment. There is evidence that busulfan can increase the risk of secondary leukaemia and can cause lung scarring.

 

New treatments

 

JAK2 inhibitors – JAK2 inhibitors block the function of the JAK2 mutation which slows down blood cell production, reduces spleen size and improves symptoms. Up to 55% of patients with ET have been found to have a JAK2 mutation. JAK2 inhibitors are being looked into as a treatment for ET.

 

Prevention of blood clots and bleeding

 

Aspirin

 

As well as being used for reducing pain and lowering temperature, aspirin is known to prevent platelets sticking together and may reduce your risk of developing a blood clot.

 

In patients with very low-risk ET, aspirin might be required. In patients with low-risk ET, treatment with low-dose aspirin is advised, especially if the patient has cardiovascular risk factors, as it has been shown to reduce both venous and arterial blood clots.

 

Research shows that aspirin is very effective at reducing risks of heart attacks and strokes in many people with different levels of risk. Patients with intermediate-risk ET and high-risk ET will be given low-dose aspirin whether they have cardiovascular risk factors or not.

 

Low-dose aspirin can have some side effects such as bleeding and indigestion. It can also cause gastric irritation, bleeding in the stomach, and ulcers. You may find that you bruise more easily and that you bleed for a long time if you cut yourself. Applying pressure to any small cut or wound with a sterile bandage will stop the bleeding. Aspirin can make the symptoms of asthma worse for those who suffer with it. In addition, some people can be allergic to aspirin.

 

Your haematologist will tell you if aspirin is safe for your particular situation and may suggest other similar medications, such as dipyridamole or clopidogrel, if necessary.

 

Anticoagulation treatment

 

Long-term anticoagulation treatment uses medication, also referred to as blood-thinners, to help prevent blood clots. This can be started if you have had a venous blood clot that has occurred with no identifiable risk factor. This will be done after your bleeding risk has been assessed.

 

Patients with ET and other MPNs more commonly have unusual sites of venous clots, meaning that the use of anticoagulation treatment can be particularly beneficial for them. These unusual sites of venous clots include:

  • The splanchnic vein – this drains the blood from the stomach, pancreas, spleen and intestines.

·         The cerebral vein – this drains blood from the brain.

 

Questions to ask your medical team about ET

 

We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here is a list of questions that may be useful to ask your medical team.

  • How can you tell if I have essential thrombocythaemia (ET)?
  • What does that mean for me? What tests will I need to have?
  • What will the tests show?
  • How long will the results take?
  • What sort of treatment will I need?
  • How long will my treatment last?
  • What happens if the treatment doesn’t work?
  • What will the side effects be?
  • Can these be managed?
  • Will I need to be off work/college?
  • Where can I get help dealing with my feelings?

 

 

Polycythaemia Vera

Myelofibrosis

Further information

We have free patient information available for MPN patients.

You can download the booklets on our information pages here.

Alternatively, you can have the information delivered free of charge by requesting it through our resources page. 

Patient stories

Further support

MPN Voice’s mission is to provide clear and accurate information and emotional support to everyone who has been diagnosed with a myeloproliferative neoplasm (MPN) and their families/friends. For further information, go to their website at mpnvoice.org.uk.

Published: October 2020

Review date: October 2023