Primary myelofibrosis (MF) is a rare cancer that causes a buildup of scar tissue, known as fibrosis, in the bone marrow. This prevents your bone marrow from producing a normal amount of blood cells.
Primary MF is a type of blood cancer. It’s one of three types of myeloproliferative neoplasms (MPN) that occur when cells divide too often or don’t die as often as they should. Other MPNs include polycythemia vera and essential thrombocythemia.
Doctors look at several factors to diagnose primary MF. You may get a blood test and a bone marrow biopsy to diagnose MF.
You may not experience any symptoms for many years. Symptoms usually only begin to occur gradually after scarring in the bone marrow worsens and starts to interfere with the production of blood cells.
Primary myelofibrosis symptoms can include:
- shortness of breath
- pale skin
- frequent infections
- easy bruising
- night sweats
- loss of appetite
- unexplained weight loss
- bleeding gums
- frequent nose bleeds
- fullness or pain in the abdomen on the left side (caused by an enlarged spleen)
- problems with liver function
- joint or bone pain
People with MF usually have a very low level of red blood cells. They may also have a white blood cell count that’s too high or too low. Your doctor may only discover these irregularities during a regular checkup following a routine complete blood count.
Unlike other types of cancers, primary MF doesn’t have clearly defined stages. Your doctor may instead use the Dynamic International Prognostic Scoring System (DIPSS) to categorize you into a low-, intermediate-, or high-risk group.
They will consider whether you:
- have a hemoglobin level that’s less than 10 grams per deciliter
- have a white blood cell count that’s greater than 25 × 109 per liter
- are older than 65 years old
- have circulating blast cells equal to or less than 1 percent
- experience symptoms such as fatigue, night sweats, fever, and weight loss
You’re considered low-risk if none of the above applies to you. Meeting one or two of these criteria puts you in the intermediate-risk group. Meeting three or more of these criteria places you in the high-risk group.
Researchers don’t understand exactly what causes MF. It’s usually not inherited genetically. That means you can’t get the disease from your parents and can’t pass it on to your kids, although MF does tend to run in families. Some research suggests it may be caused by acquired gene mutations that affect cells’ signaling pathways.
Abnormal blood stem cells in the bone marrow create mature blood cells that replicate quickly and take over the bone marrow. A buildup of blood cells causes scarring and inflammation that affects the bone marrow’s ability to create normal blood cells. This usually results in fewer than normal red blood cells and too many white blood cells.
Researchers have linked MF to other gene mutations. Around 5 to 10 percent of people with MF have an MPL gene mutation. About 23.5 percent have a gene mutation called calreticulin (CALR).
Primary MF is very rare. It occurs in only about 1.5 per every 100,000 people in the United States. The disease can affect both men and women.
A few factors may increase a person’s risk of acquiring primary MF, including:
- being over 60 years old
- exposure to petrochemicals such as benzene and toluene
- exposure to ionizing radiation
- having a JAK2 gene mutation
If you have no MF symptoms, your doctor may not put you on any treatments and instead carefully monitor you with routine checkups. Once symptoms start, treatment aims to manage symptoms and improve your quality of life.
Primary myelofibrosis treatment options include medications, chemotherapy, radiation, stem cell transplants, blood transfusions, and surgery.
Medications to manage symptoms
Several medications can help treat symptoms like fatigue and clotting.
Your doctor may recommend low-dose aspirin or hydroxyurea to reduce the risk of deep venous thrombosis (DVT).
Medications to treat low red blood cell count (anemia) linked to MF include:
- androgen therapy
- steroids, such as prednisone
- thalidomide (Thalomid)
- lenalidomide (Revlimid)
- erythropoiesis stimulating agents (ESAs)
JAK inhibitors treat MF symptoms by blocking activity of the JAK2 gene and the JAK1 protein. Ruxolitinib (Jakafi) and fedratinib (Inrebic) are the two medications approved by the Food and Drug Administration (FDA) to treat intermediate-risk or high-risk MF. Several other JAK inhibitors are currently being tested in clinical trials.
Ruxolitinib has been shown to reduce spleen enlargement and lessen several MF-related symptoms, such as abdominal discomfort, bone pain, and itching. It also reduces levels of pro-inflammatory cytokines in the blood. This may help ease MF symptoms including fatigue, fever, night sweats, and weight loss.
Fedratinib is usually given when ruxolitinib doesn’t work. It’s a very strong JAK2 selective inhibitor. It carries a small risk of serious and potentially fatal brain damage known as encephalopathy.
Stem cell transplants
An allogeneic stem cell transplant (ASCT) is the only real potential cure for MF. Also known as a bone marrow transplant, it involves receiving an infusion of stem cells from a healthy donor. These healthy stem cells replace dysfunctional stem cells.
The procedure has a high risk of life threatening side effects. You’ll be carefully vetted before you’re matched with a donor. ASCT is typically only considered for people with intermediate-risk or high-risk MF who are under the age of 70.
Chemotherapy and radiation
Chemotherapy drugs including hydroxyurea can help reduce an enlarged spleen linked to MF. Radiation therapy is also sometimes used when JAK inhibitors and chemotherapy aren’t enough to decrease spleen size.
A blood transfusion of healthy red blood cells can be used to increase red blood cell count and treat anemia.
If an enlarged spleen is causing severe symptoms, your doctor may sometimes recommend surgical removal of the spleen. This procedure is known as a splenectomy.
Dozens of drugs are currently under investigation for treating primary myelofibrosis. These include many other drugs that inhibit JAK2.
The MPN Research Foundation keeps a list of clinical trials for MF. Some of these trials have already began testing. Others are currently recruiting patients. The decision to join a clinical trial should be made carefully with your doctor and family.
Drugs go through four phases of clinical trials before receiving approval by the FDA. Only a few new drugs are currently in the phase III stage of clinical trials, including pacritinib and momelotinib.
Phase I and II clinical trials suggest that everolimus (RAD001) may help reduce symptoms and spleen size in people with MF. This drug inhibits a pathway in blood-producing cells that may lead to abnormal cell growth in MF.
You may feel emotionally stressed after receiving a primary MF diagnosis, even if you don’t have any symptoms. It’s important to ask for support from family and friends.
Meeting with a nurse or social worker can provide you with a wealth of information about how a cancer diagnosis may affect your life. You may also want to your doctor about working with a licensed mental health professional.
Other lifestyle changes can help you to manage stress. Meditation, yoga, nature walks, or even listening to music can help boost your mood and overall well-being.
Primary MF may not cause symptoms in its early stages and can be managed with a variety of treatments. Predicting the outlook and survival for MF can be difficult. The disease does not progress for a long period of time in some people.
Survival estimates range depending on whether a person is in a low, intermediate, or high-risk group. Some research suggests those in the low-risk group have similar survival rates for the first 5 years after diagnosis as the general population, at which point survival rates begin decreasing. People in the high-risk group survived up to 7 years.
MF can lead to serious complications over time. Primary MF progresses to a more serious and difficult-to-treat blood cancer known as acute myeloid leukemia (AML) in about 15 to 20 percent of cases.
Most treatments for primary MF focus on managing complications linked to MF. These include anemia, enlarged spleen, blood clotting complications, having too many white blood cells or platelets, and having low platelet counts. Treatments also manage symptoms such as fatigue, night sweats, itchy skin, fever, joint pain, and gout.
Primary MF is a rare cancer that affects your blood cells. Many people will not experience symptoms at first until the cancer has progressed. The only potential cure for primary MF is a stem cell transplant, but there are various other treatments and clinical trials underway to manage symptoms and improve your quality of life.