- Blood cancer
- Childhood leukaemia
- Acute lymphoblastic leukaemia (ALL)
- Acute myeloid leukaemia (AML)
- Acute promyelocytic leukaemia (APL)
- Chronic lymphocytic leukaemia (CLL)
- Chronic myeloid leukaemia (CML)
- Chronic myelomonocytic leukaemia (CMML)
- Hairy cell leukaemia (HCL)
- Large granular lymphocytic leukaemia (LGLL)
- Plasma cell leukaemia (PCL)
- T-cell acute lymphoblastic leukaemia (T-ALL)
- Other conditions related to blood cancer
What is myelofibrosis (MF)?
In MF, your bone marrow is overactive and then develops scar tissue (known as fibrosis). The scar tissue builds up inside your bone marrow and blood cells can’t develop properly.
When blood cell production is reduced in the bone marrow, it starts to take place in the liver and spleen instead. As the liver and spleen aren’t as good at producing blood cells, people with MF may develop anaemia (not enough red blood cells in your blood).
The spleen may also become enlarged, as it ‘holds on’ to red blood cells instead of releasing them into the blood.
People who have no history of problems with their bone marrow can get MF. This is known as primary myelofibrosis (PMF). Secondary MF is where the condition develops as a result of other blood cancers such as polycythaemia vera (PV) and essential thrombocythaemia (ET).
What causes MF?
The underlying causes of MF are still not fully understood, but you may hear your doctor talking about a genetic fault in your JAK2, CALR or MPL gene, which they think is involved in causing MF. Around 65% of patients with MF will have the JAK2 gene. 25% of people will have the CALR gene and up to 8% will have the MPL one.
All cells in your body contain a set of instructions which tell the cell what to do and when to do it, stored inside the cells in structures called chromosomes. The chromosomes are made up of a chemical known as DNA.
The DNA is arranged in sections called genes. There are 23 pairs of chromosomes in each cell in your body. When cells divide to form new cells, normally the chromosomes stay the same in each new cell.
A small genetic change to DNA can cause a genetic fault. These changes can be caused by exposure to hazardous chemicals or copying mistakes when a cell was dividing. When the JAK2, CALR or MPL gene becomes mutated, your bone marrow may not function correctly and scar tissue can build up in your bone marrow.
It’s important to note that these genetic faults happen during a person’s lifetime. As you’re not born with these faults, you can’t pass these onto your children.
The presence of one of these genes in your blood might lead doctors diagnosing you with MPN. However, we‘re learning about these faulty genes, and their impact on treatment options and outlook, all the time. If you’d like to know more about those genes, your consultant will be happy to talk to you about them.
As well as the presence of certain genetic faults, there are other factors which might lead to a higher risk of getting MF.
People who get MF are usually between 50 and 70 years old. The condition is rare in children, but can occur at any age.
Men and women are at equal risk of developing MF.
Previous diagnosis of an MPN
A previous diagnosis of PV or ET may increase the risk of getting MF, in which case it’s known as secondary MF.
Symptoms and diagnosis
Of those diagnosed with MF, 80% of people showed symptoms of MF, which led them to go to their doctor. In the remaining 20%, MF was usually picked up by chance, after a routine blood test.
- a lack of red blood cells may lead to breathlessness, fatigue, chest pains, headaches and tinnitus,
- a lack of platelets might mean you bruise easily or have unusual bleeding, and
- a lack of white blood cells might mean you get more infections than normal.
You may also have pain in your abdomen due to the enlargement of your liver and spleen.
Other symptoms may include night sweats, fevers and weight loss.
People with MF are at an increased risk of thrombosis (blood clots). Thrombosis is a serious condition and may occur in the blood vessels of your:
- brain (causing a stroke or mini-stroke/TIA – transient ischaemic attack),
- eyes (causing blurred vision or loss of vision), and
- heart (causing a heart attack).
Blood clots can also form in the veins of your legs. This is known as deep vein thrombosis or DVT. Clots can also form in the vessels in your abdomen (stomach area). If a clot dislodges and travels to the lung, it may cause a pulmonary embolism (or PE). This usually results in low oxygen levels, sharp chest pain and shortness of breath. In some cases this may be fatal.
Symptoms of a blood clot
- sudden chest pain or shortness of breath,
- swelling and/or pain in your calf on one side,
- slurred or abnormal speech, weakness in your arms or legs, or drooping on one side of your face,
- swelling in your abdomen or jaundice (your skin turning a yellow colour), and
- sudden loss of vision in one eye.
If you have any of these symptoms, you should get urgent medical attention.
Tests for MF
Most people are diagnosed with MF through a routine blood test or following a visit to their GP with symptoms. You would then have a set of tests to confirm the exact diagnosis of MF.
Full blood count
If your doctor thinks you might have MF, you’ll firstly have a simple blood test to measure the numbers of the various types of blood cells. This is called a full blood count. Your blood cells will also be examined under a microscope in a laboratory: red blood cells with a distinctive, abnormal shape can suggest to your doctor that you might have MF.
Your doctor will also examine you to check whether you have an enlarged spleen.
Tests for genetic faults
DNA from one of your blood samples will be used to test for genetic faults to the JAK2, CALR and MPL genes. Around 50% of MF patients have a fault in the JAK2 gene and 30% have a fault in the CALR gene. However, some people won’t have one of these faults, so a diagnosis can’t always be confirmed after these tests.
Bone marrow biopsy
Some people need tests on their bone marrow before their doctors can make a diagnosis. This helps to rule out any other bone marrow problems and lets doctors assess your fibrous tissue.
During the test, a small amount of bone marrow is taken using a needle from the hip bone. You don’t need to stay overnight in hospital for this; you can have it as an outpatient using local anaesthetic or mild sedation. It’s usually quite quick but will be uncomfortable while the sample’s being taken from the marrow; you can take painkillers if you need to. Your doctors will then look at the bone marrow sample under a microscope to assess it for any disease which might be in it.
Bone marrow trephine
As a patient with MF will have a large amount of fibrous tissue in their bone marrow, it may be hard to get a sample using a needle and syringe – this is known as a ‘dry tap’. This means you may need a trephine biopsy.
This is where a ‘core’ of bone marrow from the hip bone is taken, under local anaesthetic or mild sedation. This provides information about the structure of your bone marrow and the number and distribution of the different blood cell types – and cancer cells, if present.
Once a diagnosis has been confirmed, your doctor will do tests to find out how much the MF has progressed.
Some people will be in the early proliferative (or cellular) phase.
At this stage:
- Your bone marrow will be overactive with increased numbers of platelet-producing stem cells (megakaryocytes).
- There will be a slight increase of fibrin in your blood (the protein that forms when the blood clots, and disrupts the flow of blood through the fibrous network).
- Blood counts will be very high at this stage. Your doctor will conduct detailed tests to distinguish MF from leukaemia. Your doctor will explain these tests to you if you need to have them.
At this stage, there is:
- An increase in the amount of fibrosis in your bone marrow.
- A decrease in the amount of normal blood-forming tissue.
The structure of the bone marrow changes which in turn leads to a reduction in the mature cells in your blood (red cells, platelets and/or white cells).
Acute myeloid leukaemia
In a some people, MF can progress to acute myeloid leukaemia.
Treatment and side effects
The treatment you have will depend on a variety of factors, including:
- your blood counts,
- the symptoms you have, and
- your overall fitness.
You should be monitored for cardiovascular risk factors such as diabetes, high cholesterol, high blood pressure and smoking, as these should be addressed as effectively as possible.
The main aim of treatment is to control any symptoms you have. If you’ve been diagnosed with MF and don’t have any symptoms, you may not need to start treatment for a while. Instead, you'll be monitored with regular check-ups and blood tests; this is known as 'watch and wait'. While this might seem strange, there’s no evidence to show that treating people with no symptoms has any impact on their outcome. It also means you don’t get any side effects from unnecessary treatment.
If you have severe anaemia you’ll need regular blood transfusions, usually every one to three months. These can be carried out during a single day and you would need to stay in hospital overnight. You might also have platelet transfusions if you have low platelets and you’re having unusual bleeding or bruising.
Ruxolitinib is a type of drug known as a JAK2 inhibitor. It is recommended for people with an enlarged spleen or troublesome symptoms of myelofibrosis. It can reduce the size of your spleen, improve symptoms and improve your overall outlook. It is taken as tablets, twice a day, for as long as it is working. Possible side effects include anaemia, a low platelet count, a low white blood cell count and increased risk of infections. Your doctors will monitor your response to ruxolitinib. They may need to change the dose or stop ruxolitinib if it’s not working well for you.
Treatment for enlarged spleen
An enlarged spleen may cause you problems by becoming painful. It may also cause anaemia.
To treat an enlarged spleen, you may receive local radiation. This would usually reduce the size of your spleen from anywhere between a few months to a couple of years.
Another option may be to have an operation to remove your spleen (a splenectomy). There can be complications after a splenectomy: your doctor will discuss the pros and cons with you to help you decide if the procedure is right for you.
If your platelet count is high or you have other symptoms such as weight loss or sweats, you may be given tablets called hydroxycarbamide (or hydroxyurea) to take. This is a mild form of chemotherapy and works by directly preventing the production of red blood cells. Hydroxycarbamide is the most common chemotherapy drug used to treat MF.
You might get some side effects from this treatment. These might include more infections than normal, diarrhoea or constipation. Your healthcare team will be able to help you manage side effects like this.
Hydroxycarbamide is a very safe treatment. However, there’s a theoretical risk that it may increase the risk of MF transforming into acute myeloid leukaemia if it’s used as a long-term treatment. For many people, it’s felt that the benefits of the treatment outweigh any potential small risk involved.
Drugs called JAK2 inhibitors are now available to treat MF. These can reduce the size of your spleen, improve symptoms and your overall outlook. However, JAK inhibitors may worsen anaemia.
The length of time you take the drug for depends on how well it works and any side effects you get from it. Your doctor can discuss if these medications would be appropriate treatment for you.
Thalidomide is a targeted therapy to treat MF. Thalidomide can cause birth defects, so it shouldn’t be given to pregnant women. People taking thalidomide who are sexually active should use a barrier form of contraception as some hormonal methods of birth control (such as the pill) can be made less effective by thalidomide.
You may also get side effects from this treatment such as feeling tired or drowsy, constipation and numbness or tingling in your hands and feet.
The length of time you take the drug for depends on how well it works and any side effects you get from it. The use of thalidomide is becoming less common in the UK.
You may be given danazol to help improve anaemia (low number of red blood cells). The length of time you take the drug for depends on how well it works and any side effects you get from it.
Donor stem cell transplant
A stem cell transplant is what used to be called a bone marrow transplant. It aims to give patients healthy stem cells, which then produce normal blood cells.
It isn’t a suitable treatment for most MF patients due to the risks associated with the procedure. For a minority of patients – especially those whose disease is progressing more quickly – a transplant may provide a cure, but there isn’t enough evidence to be sure of this yet.
There are two main types of stem cell transplant:
- Autologous or autograft – this uses the patients’ own stem cells.
- Allogeneic or allograft – this uses donor stem cells and is a high risk procedure.
The outlook for people with MF can vary. Some people may have a mild form of MF that doesn’t progress rapidly. For others, MF progresses more quickly and requires regular blood transfusions or drug treatments. Around 20% of people with MF go on to develop acute myeloid leukaemia. Sometimes it’s possible to treat MF with a stem cell transplant.
Although it’s impossible to say what will happen to an individual person, your healthcare team will think about prognosis to help them make the best treatment decisions with you. They will consider various factors such as:
- your age,
- levels of blood cells in the blood,
- severity of symptoms, and
- the particular genetic mutations you have.
All of these things can have an impact on your prognosis.
You may find it hard to ask or talk about your prognosis. Sometimes those close to you might want to know your prognosis even if you don’t. However, your healthcare team aren’t allowed to give this or any other information to anyone – not even family members – without your permission. Try to decide early on who you want to know about your condition, then tell your healthcare team – you can change your mind any time.
Remember that your outlook might change, for example if you respond well to treatment. If there’s a change in your condition, or if you’ve finished all or part of your treatment, you might want to consider asking if your prognosis is still the sam