Myelofibrosis (MF)

As times goes on, we are learning more about MF. However, what causes MF is not fully understood.

One of the features of the disease that we do know is dysregulated signaling in haematopoeitic stem cells (cells in the bone marrow that make your blood cells). One of the signaling pathways that has been found to be frequently involved (in about 50-60% of patients) is called ‘JAK-STAT,’ which means there is a change in JAK2.

However, even MF patients who do not have this JAK2 mutation may still have dysregulated ‘JAK-STAT’ signaling that underlies their disease.

A further 25% of patients have a mutation in a gene called calreticulin-R (CAL-R) and about 5% of patients have mutation of a gene called MPL.

New genetic mutations are still being discovered and it is likely that, in most patients, the disease is caused by a combination of these mutations.

Risk factors:

• Age: MF is most commonly diagnosed in patients aged between 60 and 70 years old.
• Radiation and chemical substances: In a tiny proportion of patients, the mutations can be linked to past exposure to this type of very high energy radiation (such as medical X-rays) or to substances such as benzene and toluene.
• Genetics: It is important to note that MF is rarely inherited and it not passed from parent to child, although some families do seem to develop the disease more readily than others.

In someone with MF, abnormal stem cells take over the bone marrow, leading to chronic inflammation and fibrosis (scarring). Through the bone marrow not being able to make normal blood cells, the spleen and liver (and sometimes other organs) try to compensate by producing red blood cells. As a result, the spleen can become enlarged.

Enlargement of the spleen may cause abdominal pain, discomfort, loss of appetite and a feeling of filling up quickly during meals.

Due to the lack of blood cells being produced in the bone marrow, there are a number of conditions that are common in MF patients:

• Anaemia – low number of red blood cells
• Neutropenia – low number of white blood cells
• Thrombocytopenia – low number of platelets.

The most common symptoms of MF include:

• Fatigue
• Sweats (which may be predominantly at night)
• Itching (pruritus) – this may be worse after baths or showers
• Bone pain (arthralgia)
• Muscle pain (myalgia)
• Weight loss
• Fever

Diagnosis will usually be made following a number of tests, these may include:

• Full Blood Count (FBC) – this is used to measure the number of red cells, different types of white cells and platelets, usually done so under a microscope through a ‘blood film.’
• Bone marrow biopsy – in most cases, this is used to confirm a MF diagnosis. This is usually taken from the hip bone while under local anaesthetic.
• Tests for Gene Mutations – blood tests are conducted to test for mutations in genes such as JAK2, CAL-R and MPL.
• Abdominal ultrasound scan – this is done to look for spleen enlargement (if it is not large enough to be felt), liver enlargement or abnormalities of other organs.

Your personal situation, health history and the ways in which you respond to treatment can all affect your prognosis.

Prognostic scoring systems are used by doctors, either at the time that the diagnosis of MF has been made (International Prognostic Scoring System, IPSS) or at later points during the course of the disease (Dynamic International Prognostic Scoring System, DIPSS or DIPSS Plus). Generally, these systems allow MF to be categorized as ‘low risk’, ‘intermediate-1’, ‘intermediate-2’ or ‘high risk’.

Certain factors may influence prognosis and will be used by your doctor to calculate your score:

• The degree of anaemia (lowering in the number of red blood cells) and whether blood transfusions are needed to treat this
• The number of blast cells (cells which are in the early stages of development and do not carry out any function) in the blood
• Your age
• Whether the white blood cell count is raised
• The presence of ‘constitutional symptoms’
• The DIPPS Plus score also takes into account lowering of platelet count and whether ‘cytogenetic changes’ (changes in the chromosomes that contain the genetic material) are seen in the bone marrow
• The presence of certain genetic mutations

The majority of treatments for MF are aimed at managing symptoms and reducing complications, so that your quality of life is better.

• Bone marrow or stem cell transplant

Due to the high risk of life-threatening side effects and the risk of new stem cells reacting against your body’s healthy tissues, transplants are not commonly recommended. The first step, known as ‘conditioning’, involves high levels of chemotherapy or radiation therapy.

In general terms, all other treatments can be divided into two main groups of treatments:

1. Treatments that are used to reduce the size of the spleen and to improve constitutional symptoms

• Chemotherapy (using Hydroxycarbamide, JAK inhibitors or Melphalan, Busulphan, Cladribine or Radioactive Phosphorous)
• Splenectomy (surgical removal of the spleen)
• Radiotherapy (using high-strength beams such as X-rays)

2. Treatments that are used primarily to treat anaemia and to improve low blood counts:

• Blood transfusions
• Erythropoiesis-stimulating agents (ESAs, a growth factor protein which stimulates the bone marrow to make red blood cells)
• Thalidomide (a type of biological therapy, usually taken in combination with steroid tablets)
• Danazol (synthetic form of male hormones, androgens)
• Interferon Alpha

Many alternative treatments for MF are being actively investigated, such as other JAK inhibitors including inhibitors of a pathway known as the Hedgehog pathway, telomerase inhibitors and histone deacetylase inhibitors. In years to come, it is likely that there will be many more treatment options available to patients.

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

• How can you tell if I have myelofibrosis?
• 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?

We have free patient information available for MF.

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.