Myelofibrosis (MF)

What is myelofibrosis (MF)?

MF is caused by abnormal blood stem cells in the bone marrow. These abnormal stem cells produce more mature cells that grow quickly and take over the bone marrow, causing both fibrosis (scar tissue formation) and chronic inflammation. As a result, the bone marrow becomes less able to create normal blood cells and blood cell production may move to the spleen and liver.

 

Who does MF affect?

Primary MF (which means it occurs on its own) usually develops slowly in people aged between 60 and 70. One third of people diagnosed with MF have been previously diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET). This is known as secondary MF and more specifically as post-PV MF or post-ET MF.

 

How is it diagnosed?

A sample of blood is checked under a microscope for red blood cells that are shaped like tear drops. The number and types of white blood cells, the number of platelets and the presence of immature blood cells can also help your doctor diagnose MF. Your doctor will use cytogenetic testing to check for other signs, including mutation in the JAK2, CALR or MPL genes.

 

What are the symptoms?

As your bone marrow isn’t able to make normal blood cells your spleen and liver usually try to compensate, however they, can’t compensate sufficiently. The lack of normal blood cells causes low blood count which leads to anaemia, which can make you feel very tired and short of breath. Low white blood cell count or diminished production of antibodies can place you at a higher risk of infections. Also, your liver and spleen can end up swelling. Symptoms of MF can include:

  • Symptoms of anemia (low red blood count), including weakness and fatigue, shortness of breath, palpitations and pale skin
  • Symptoms associated with an enlarged spleen, including pain and discomfort below your ribs on the left side of your body, feelings of fullness, indigestion, loss of appetite and weight loss
  • Symptoms associated with an enlarged liver, typically pain and discomfort in your stomach or abdomen
  • Skin itchiness (your doctor might call this pruritus)
  • Excessive sweating, especially at night
  • Fever
  • Increased risk of infection
  • Bleeding and easy bruising
  • Bone pain

 

What causes MF? 

As time goes on, we are learning more about MF and its causes. What causes MF is not fully understood. About 50% to 60% of MF patients have a change (mutation) in a protein that regulates blood cell production (this protein is known as JAK2 and the mutation as JAK2 V617F).
This mutation causes JAK2 to signal blood cells to grow and divide even when the body is not asking for more blood cells which dysregulates the JAK/STAT pathway involved in the blood cell production process in the bone marrow. 5% to 10% of MF patients have a mutation in a gene named MPL, which also affects the JAK/STAT pathway. In 2013 another gene mutation called CALR was discovered. It affects about 24% of MF patients. Research is ongoing to determine how the CALR mutation affects the treatment and prognosis for MF patients.

People are not born with these mutations but acquire them during their lives. These mutations may also be triggered by past exposure to ionizing radiation (a type of radiation that has very high energy, like medical X-rays) or to petrochemicals such as benzene and toluene. It is also important to note that MF is rarely inherited and is not passed on from parent to child, although some families do seem to develop the disease more readily than others.

 

What will my doctor do?

Your doctor will tailor the management of your MPN to your particular case. When you’re first diagnosed, they may suggest the “watch and wait” approach, if you don’t have symptoms or complications such as anemia or an enlarged spleen. This means your MPN and related symptoms will be monitored regularly through check-ups and blood tests.

 

What’s the outlook?

MF is generally regarded as incurable and the course of MF can vary considerably between people. In some people the disease remains stable for long periods, allowing them to live a normal life with minimal interruptions. For others, MF progresses more quickly and people require treatment to help relieve symptoms. Up to 20% of cases may transform into acute myeloid leukaemia (AML), a cancer. If you’d like to know more about your individual prognosis, you should talk to your doctor.

 

Prognostic Indicators

Doctors and scientists have been developing methods to predict disease prognosis for myelofibrosis patients. One of the methods is referred to as DIPSS (Dynamic International Prognostic Scoring System). The following factors are considered in this scoring system (one point for each except Hemoglobin which is two points)

  • Age: > 65
  • White blood cells (Leukocytes): > 25 X 109 /L
  • Hemoglobin: < 100 g/L  – TWO POINTS
  • Constitutional Symptoms (fatigue, bone pain, pruritis (itchiness), etc.)
  • Blast cells: > 1%
DIPSS Risk and Survival
Number of Risk Points Risk Category Median Survival (years)
0 Low Not reached
1-2 Intermediate 1 14.2
3-4 Intermediate 2 4
5-6 High 1.5