Primary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN). MPNs are blood cancers in which the body makes too many blood cells that don’t function correctly. Myelofibrosis causes fibers to build up in the bone marrow (the soft tissue found inside certain bones). Primary myelofibrosis is also sometimes called chronic idiopathic myelofibrosis.

Myelofibrosis may develop from the other classic types of MPNs, including polycythemia vera or essential thrombocythemia. In such cases, it is called secondary myelofibrosis. Myelofibrosis that develops on its own is called primary myelofibrosis. Symptoms and treatments for primary and secondary myelofibrosis are usually the same.

There are about 18,000 people in the United States currently living with MF. Most people who develop MF are 60 years or older.

What Causes Primary Myelofibrosis?

PMF develops from abnormal stem cells in the bone marrow. Stem cells make all of the body’s blood cells. In MPNs, stem cells develop gene changes that cause them to produce too many blood cells that don’t work properly. Each type of MPN leads to high levels of a different type of blood cell. In PMF, people have too many abnormal megakaryocytes. Megakaryocytes are giant cells in the bone marrow that make platelets, which are responsible for clotting the blood.

Abnormal PMF megakaryocytes release molecules that encourage other cells in the bone marrow to make fibers such as collagen. In healthy bone marrow, small amounts of collagen provide a structure that cells can grow on. People with PMF have too many of these fibers, which is called fibrosis. Collagen is also involved in making new scar tissue after the body is injured, which is why doctors sometimes say that myelofibrosis leads to scarring in the bone marrow.

When webs of collagen fill up the bone marrow, they crowd out all of the other cells. Stem cells have trouble making new blood cells, leading to low levels of healthy cells in the blood.

Gene Changes in Primary Myelofibrosis

There are many gene changes found in abnormal PMF cells. However, researchers have identified three main changes that seem to be responsible for causing PMF:

• About 65 percent of people with PMF have changes in the Janus kinase 2 (or JAK2) gene.
• About 25 percent of people with PMF have changes in the calreticulin (or CALR) gene.
• About 10 percent of people with PMF have changes in the myeloproliferative leukemia (or MPL) gene.

Although each of these genes has a slightly different role within the body, mutations in these genes usually all have the same effect in PMF: They cause stem cells to produce too many megakaryocytes.

Risk Factors

Because PMF develops from gene changes, things that damage a cell’s DNA can increase a person’s chances of developing PMF. Exposure to high levels of radiation or to certain chemicals, such as benzene and toluene, can increase PMF risk. Additionally, risk increases with age because gene mutations tend to build up over the course of a person’s life.

Primary Myelofibrosis Symptoms

Many symptoms of PMF develop because there’s not enough room in the bone marrow to make new blood cells. As a result, levels of normal blood cells drop, and the spleen and the liver try to compensate by making blood cells.

PMF doesn’t usually cause symptoms in the early stages of the disease. This means that some people may be diagnosed with myelofibrosis before they notice any health changes. Eventually, however, PMF usually causes signs and symptoms including:

• Fever
• Night sweats
• Weight loss
• Itchy skin
• Bone or joint pain
• Anemia (low red blood cell count), leading to tiredness, pale skin, and shortness of breath
• Thrombocytopenia (low levels of platelets), which can cause easy bruising, bleeding problems, and petechiae (tiny purple, red, or brown spots caused by bleeding under the skin)
• Neutropenia (low levels of a type of white blood cell called a neutrophil), leading to frequent infections
• Splenomegaly (enlarged spleen), which may lead to pain or feelings of fullness on the upper left side of the abdomen

These symptoms can also frequently be caused by other health conditions. Having any of these signs or symptoms does not necessarily mean you have PMF. However, if you are noticing any changes to your health, you should talk to your doctor.

Diagnosing Primary Myelofibrosis

Several tests are used to diagnose PMF. Usually, a combination of physical exams and blood and bone marrow tests are needed.

During a physical exam, the doctor may ask about medical history, including previous health conditions, current symptoms, and medications. The doctor can also look for signs of PMF such as a large spleen size or signs of muscle loss.

If a doctor suspects that a person may have PMF, they will recommend several blood tests. There are a few possible tests that can help with diagnosis:

• A complete blood count measures numbers of each type of blood cell and can identify signs such as anemia.
• Peripheral blood smears, in which a doctor examines blood cells under a microscope, show whether any of the cells in the blood look abnormal.
• A comprehensive metabolic panel measures levels of certain molecules that indicate whether a person’s organs are working as they should.

MPNs are also typically diagnosed using bone marrow tests. During a bone marrow aspiration, a small sample of liquid is removed from inside the bone. During a bone marrow biopsy, a sample of cells is taken. Using these tests, the doctor can look for signs of PMF including fibrosis and large numbers of megakaryocytes.

Blood and bone marrow samples may be used for genetic tests. Knowing which gene changes are present within cells helps the doctor plan treatment and tell MPNs apart from other blood cancers.

Primary Myelofibrosis Outlook

Primary myelofibrosis can look very different from person to person. An individual prognosis (outlook) is estimated based on factors that can increase or decrease the risk of having a worse outcome. These factors are measured using a scoring system called the Dynamic International Prognostic Scoring System. Risk factors that may lead to a lower chance of recovery include:

• Older age (more than 65 years old)
• Very low levels of red blood cells and platelets
• High levels of immature white blood cells
• Needing blood transfusions to relieve symptoms
• Certain gene changes
• Having constitutional symptoms, which include fever, night sweats, and weight loss

Doctors place people with PMF into groups based on how many of these risk factors they have. Determining whether a person is low-risk, intermediate-risk, or high-risk helps a doctor recommend a treatment plan. Risk groups also help estimate a person’s outcome. People in lower-risk groups often live longer:

• For people with low-risk PMF (no risk factors), median survival time is 15.4 years after diagnosis.
• For those in the intermediate-1 risk group (one risk factor), median survival time is 6.5 years.
• For individuals in the intermediate-2 risk group (two or three risk factors), median survival time is 2.9 years.
• People with high-risk PMF (four or more risk factors) have a median survival time of 1.3 years.

PMF may lead to other health problems in the future. About 1 out of 5 people with PMF will develop acute myeloid leukemia within 10 years of diagnosis. Myelofibrosis also increases a person’s risk for bleeding problems, painful or swollen joints, or the formation of tumors in other parts of the body.

Treatments for Primary Myelofibrosis

Some people with PMF don’t have symptoms and don’t need to undergo treatment right away. Others may need to begin treatment immediately after diagnosis. In either case, people with PMF need to have frequent doctor’s visits so that their health care team can look for any signs that the condition is getting worse.

Drug Treatments

Jakafi (ruxolitinib) was the first drug approved by the U.S. Food and Drug Administration (FDA) for treating myelofibrosis. It is a targeted therapy that can help relieve PMF symptoms. It is usually used for people in intermediate- or high-risk groups, and it may sometimes be recommended for people with low-risk PMF who have symptoms.

Inrebic (fedratinib) is another targeted therapy drug that can reduce PMF signs and symptoms. It is used to treat people with intermediate- or high-risk primary PMF, as well as people with secondary PMF.

Stem Cell Transplant

Although drug treatments may help keep PMF under control, they do not cure the disease. The only treatment option that can cure PMF is a stem cell transplant. However, this treatment can lead to serious side effects, and it is usually only an option for people who are younger and don’t have other health conditions.

During an allogeneic stem cell transplant, a person’s old, abnormal stem cells are destroyed with high doses of radiation therapy or chemotherapy. Next, the person receives new stem cells from a donor, which go on to produce healthy blood cells. This procedure can get rid of all of the damaged cells that were causing PMF.

Palliative Treatments

Palliative care is a branch of medicine that focuses on treating the symptoms of a chronic illness. Palliative treatments can help people with PMF have a better quality of life. These treatments are not the same as end-of-life care — they can be used at any stage of a person’s disease, along with other treatments that aim to treat or cure the condition.

Signs and symptoms of PMF can be treated with a variety of options:

• Doctors may treat anemia with steroid or hormone medications, Revlimid (lenalidomide), Thalomid (thalidomide), erythropoiesis-stimulating agents, or blood transfusions.
• Splenomegaly can be treated with Intron A (interferon alpha-2b), hydroxyurea, radiation therapy, or splenectomy (surgical removal of the spleen).
• Blood clots can be prevented with low-dose aspirin or hydroxyurea.

Clinical Trials

Some people with PMF may be able to participate in a clinical trial. Researchers use clinical trials to test new medications or investigate new drug doses or combinations. People with PMF who join clinical trials may be able to access new treatment options that work better than current therapies. Researchers are currently studying additional targeted therapy drugs for PMF as well as medications that treat fibrosis.

Talk With Others Who Understand

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