Myelofibrosis

In this video, Albert talks about how he came to be diagnosed with myelofibrosis and how it’s affected his life. Albert is taking a new drug that is under trial to treat myelofibrosis. This drug is a JAK2 inhibitor. Albert is very pleased with how he’s doing on this new medication. You can read more about JAK2 and the inhibitor trials on our Research pages.

Read on below the video to find detailed information about myelofibrosis.

About myelofibrosis

Myelofibrosis (MF) is a disorder which affects the way blood cells are produced in the body. People over age sixty are most likely to have this disease, with men and women equally at risk.

Myelofibrosis affects the bone marrow – the “factory” inside our bodies which produces blood cells. Myelofibrosis causes scar tissue and fibrous tissue to build up inside the bone marrow, so that the marrow can’t produce blood cells effectively.

In myelofibrosis, there are too many fibroblasts in the marrow. Fibroblasts are cells which produce connective tissue, scar and fibrous tissue. The excess fibroblasts scar the bone marrow and stop the bone marrow from making blood cells.

Types of myelofibrosis

Myelofibrosis can develop in several ways:

  • Primary The disorder can develop spontaneously on its own. In this case we call the disorder “primary” or “idiopathic” myelofibrosis (PMF).
  • Post MPD People may develop myelofibrosis after they have had another myeloproliferative disorder (MPD) for some time. If MF develops after someone has had essential thrombocythaemia (ET) or polycythaemia vera (PV), we call the disorder “post ET” or “post PV” myelofibrosis.
  • After another disease Myelofibrosis sometimes develops as a result of another disease such as autoimmune or inflammatory conditions, cancers like Hodgkin’s disease, tuberculosis or damage caused by radiation.

Myelofibrosis is also sometimes called agnogenic myeloid metaplasia or idiopathic myelofibrosis but these are old-fashioned terms and not often used nowadays.

Causes

Recent research shows that about 50% of people with myelofibrosis have a mutation (or change) in a protein called JAK2, a protein that regulates blood cell production. Viral infections or radiation damage may cause this mutation to occur.

There are other mutations that sometimes occur in myelofibrosis, but these are far less common. Under 10% of patients may have mutations in other proteins. The most common of these other mutations is called MPL.

We are learning more but additional more research needs to be done to determine the causes of MF.

Diagnosis

Symptoms

About 20% of people with myelofibrosis do not exhibit any symptoms. Their condition may be found by chance, for instance during a routine blood test. The other 80% of people diagnosed with MF may experience some of the following symptoms:

  • Excessive tiredness, weakness or shortage of breath as a result of anameia
  • Enlarged liver
  • Pain or fullness below the ribs due to an enlarged spleen
  • Easy bruising or bleeding
  • Excessive sweating especially during sleep (night sweats)
  • Bone pain
  • Frequent infections
  • Unexplained weight loss
  • Heavy periods

Diagnostic tests

Your haematologist may recommend some of the following tests to confirm a diagnosis of myelofibrosis:

  • Full blood count (blood test) Your haematologist will review your full blood count for signs of high blood cell counts or low total blood count (called “pancytopenia”). In the early phase of the disease, your bone marrow may be overactive and make too many blood cells. This phase occurs before the fibrous scarring begins to become very prominent and damages the bone marrow. In later stages of the disease, blood cells counts may be low.
  • JAK2 test Your haematologist can test your blood to see if you have a change of gene called JAK2 V617F mutation. About 50% of people with MF show this mutation. Your haematologist may also test for other possible mutations in the same way.
  • Abdominal ultrasound If your haematologist suspects that you may have myelofibrosis, he or she will check to see if your spleen is enlarged. This is because in MF your spleen may begin to produce blood cells, and these collect inside the spleen. The ultrasound is a painless test.
  • Bone marrow biopsy (BMB) A bone marrow biopsy is a test of your bone marrow that is done in the hospital. You will not need stay overnight in the hospital, and you will generally just need local anaesthesia. Your haematologist will give you some medication to prevent pain, and then he or she will extract some bone marrow from your hip bone using a needle. The bone marrow tissue can then be examined in a laboratory so that your haematologist can see how the stem cells in your bone marrow are working, and if there is any fibrosis in your marrow.

Treatment

The main aims of the treatment are to control symptoms of the disease, including low blood counts and the size of the spleen. Additional treatments may be considered to control the disease as it progresses.

Treatment to control symptoms

These treatments will help to reduce the unpleasant symptoms you may experience with myelofibrosis, such as fatigue.

  • Blood Transfusions Your consultant will use blood transfusions to treat severe anaemia. If your platelet count is very low or if you have problems with bleeding, you may need platelet transfusions .
  • Danazol Danazol is a hormone that is made naturally by the body. This hormone can stimulate the production of red cells and can sometimes make the haemoglobin level rise. Some patients are given danazol to prevent the need for blood transfusions. This drug is given orally. Side effects include weight gain due to fluid retention and a slight increase in facial hair growth in women. It can also affect the liver or kidneys.
  • Erythropoetin Sometimes anaemia is the main problem for MF patients. In this case treatment with erythropoetin (EpO) can be effective. EpO is the hormone naturally produced by the body that stimulates the bone marrow to make red cells. This drug is given by injection under the skin.
  • Aspirin Low-dose aspirin (75mg once a day) may be given if the platelet count is high and there is a risk of blood clots (thrombosis).
  • Splenectomy/Splenic Irradiation If the main symptom is abdominal pain and discomfort due to a very large spleen, or if the need for blood and platelet transfusions is very high, or if there is no response to medical treatment, it may be beneficial to remove the spleen. There are risks of bleeding and infections with this operation. Occasionally radiotherapy can be given to try to reduce the size of the spleen.

Treatments to control disease progression

There are some treatment options that try which can reduce the rate at which the disease progresses. These include:

JAK2 inhibitors

Some people with myelofibrosis may be eligible to enter drug trials. New drugs that act to inhibit the action of mutated JAK2 protein are now under trial in the US and in the UK and Europe. You can read more about the newest treatments in our Research section.

Bone Marrow Transplants (BMT)

Bone marrow transplants are the only treatment that can cure MF, but have significant risks. Read more about bone marrow transplants in our Treatments section.

Complications

There are a number of complications associated with myelofibrosis:

  • Fatigue Anaemia can cause fatigue.
  • Spleen enlargement A enlarged spleen can cause discomfort and shortness of breath.
  • Gout MF can increase the body’s production of uric acid which in turn can cause joint pain and inflammation.
  • Infections Myelofibrosis can reduce the production of white blood cells, cells that fight off infection. Mutated or overproduction of white cells or insufficiently formed white cells will lead to a decreased ability of your body to resist infections.
  • Bleeding complications In advanced stages of myelofibrosis, a lower platelet count or impaired platelet function may lead to uncontrolled or easy bleeding or bruising.
  • Inflammation/hardening of bone tissue Bone marrow and tissue can become hardened or inflammed resulting in severe pain and joint tenderness.

Prognosis

Myelofibrosis is a progressive disorder which is irreversible in most cases.

What determines prognosis

The prognosis depends on your age, the results of your blood and bone marrow tests and your symptoms. Your haematologist can evaluate your haemoglobin level, white cell count, age and bone marrow cytogenetic (chromosome or genetic analysis) results and will take all these factors into account to decide your prognosis and appropriate treatment regime.

Prognosis varies by person

The progression of MF is very variable. People in a good prognostic group can have up to at least fifteen years of being well. Those in the poor prognosis group may have a survival of about twelve to eighteen months.

Up to 25% of MF patients may develop acute myeloid leukaemia (AML), a type of blood and bone marrow cancer that progresses rapidly.

Scoring system

A scoring system is often used by haematologists to gauge prognosis the most recent one relies upon whether any other the following factors are present:

  • White cell count OVER 25
  • Haemoglobin LESS than 100g/L or 10g/dl
  • Blasts (immature cells in blood) MORE than 1%
  • Disease related symptoms
  • Age over 65 years

Your haematologist may give you a prognostic score. These scores are divided into low, intermediate 1, intermediate 2 or high risk disease. People with high risk disease have a shorter life expectancy. Up to 25% of people with myelofibrosis may develop acute myeloid leukaemia (AML); this a type of blood and bone marrow cancer that progresses rapidly and has a poor prognosis. As prognosis can vary significantly from patient to patient, it’s best to talk with your haematologist for information specific to your situation.