Myelofibrosis Overview

Myelofibrosis is a rare, chronic blood disorder classified as a myeloproliferative neoplasm, a group of conditions characterized by abnormal blood cell production in the bone marrow. In myelofibrosis, excessive scar tissue forms in the bone marrow, disrupting the body’s ability to produce healthy red blood cells, white blood cells and platelets.

How does myelofibrosis start?

Most cases of myelofibrosis are driven by a genetic mutation that is acquired during life rather than inherited. The mutation affects the proteins involved in blood cell signaling and growth, leading to uncontrolled cell production and inflammation. Over time, inflammatory signals can stimulate the buildup of fibrous tissue in the bone marrow, gradually impairing blood cell formation.

As the bone marrow becomes less effective at creating new blood cells, the body may attempt to produce blood cells in other organs, such as the spleen and liver, which can lead to organ enlargement and other complications.

Myelofibrosis may develop on its own, which is known as primary myelofibrosis. It can also evolve from another myeloproliferative neoplasm, such as polycythemia vera or essential thrombocythemia. This is referred to as secondary myelofibrosis.

How common is myelofibrosis?

Myelofibrosis is relatively uncommon, affecting an estimated 1 to 2 people per 100,000 worldwide, with approximately 1,200 to 1,500 new cases diagnosed each year in the United States. Although it can occur at any age, the condition is most often diagnosed in adults 50 and older.

What is the prognosis for myelofibrosis?

The prognosis for myelofibrosis can vary widely based on factors such as the specific genetic mutation and the patient’s age, symptoms, blood counts and overall health. Some people live many years with mild symptoms, while others may experience a more aggressive disease course. The healthcare team may use a risk-stratification system that uses data such as clinical history, demographics, social factors and behaviors to estimate the outcome and guide treatment decisions.

How does myelofibrosis impact the patient’s body?

As healthy blood cell production declines due to myelofibrosis, the patient may develop anemia, recurrent infections or bleeding complications. Enlarged organs, particularly the spleen, can cause discomfort, early satiety and abdominal pain. In some cases, myelofibrosis can potentially progress to acute leukemia.

What are the causes and risk factors for myelofibrosis?

In many cases, the precise cause of the acquired genetic change that leads to myelofibrosis is unknown. The genes most commonly affected are those involved in blood cell growth and signaling. These include:

• JAK2 – A harmful change in the JAK2 gene is found in approximately 50% of people diagnosed with myelofibrosis. This mutation causes overactive signaling that leads to abnormal blood cell production.
• CALR (calreticulin) – A mutation in the CALR gene is found in a significant number of myelofibrosis patients who do not have a JAK2 mutation. This genetic change drives abnormal cell growth in the bone marrow.
• MPL – Less common than JAK2 and CALR mutations, an MPL mutation affects the thrombopoietin receptor, which plays a key role in platelet production.

Additional mutations in certain genes, such as ASXL1, TET2, EZH2, SRSF2, IDH1 and IDH2, can influence the behavior and prognosis for myelofibrosis.

Is myelofibrosis preventable?

There is no known way to prevent myelofibrosis. Because the condition stems from an acquired genetic mutation, prevention strategies are limited. Reducing exposure to toxic chemicals and maintaining overall health may help lower the risk of cancer in general, but these steps have not been proven to prevent myelofibrosis specifically.

What are the signs and symptoms of myelofibrosis?

The signs of myelofibrosis can vary significantly. Some people have no symptoms early on, while others experience noticeable effects related to abnormal blood counts or organ enlargement.

What are the early warning signs of myelofibrosis?

Early-stage myelofibrosis is often asymptomatic. When symptoms do occur, they are often mild and related to anemia or inflammation.

Possible early warning signs include:

• Unusual fatigue or weakness
• Shortness of breath with physical activity
• Pale skin
• Mild abdominal discomfort
• Unexplained weight loss

What are the most common symptoms of myelofibrosis?

Over time, the symptoms of myelofibrosis may become more pronounced. Common signs include:

• Chronic fatigue
• Fever
• Night sweats
• Bone or joint pain
• Anemia
• Easy bruising or bleeding
• Abdominal fullness due to spleen enlargement

What are the signs of advanced myelofibrosis?

As myelofibrosis progresses, it can potentially lead to serious complications due to severe bone marrow failure or organ involvement. Possible symptoms include:

• Severe anemia requiring blood transfusions
• Marked spleen enlargement
• Frequent infections
• Significant weight loss
• Worsening bone pain

What are the signs that myelofibrosis has progressed?

Although myelofibrosis does not metastasize like other cancers that form solid tumors, it can still advance or transform. Signs of cancer progression may include:

• Rapidly worsening blood counts
• Increasing spleen size
• Development of acute leukemia
• Escalating symptoms despite treatment

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How is myelofibrosis diagnosed?

Typically, myelofibrosis is diagnosed through a combination of clinical evaluation, laboratory testing and bone marrow examination. The diagnostic process often begins after abnormal blood counts are discovered during routine testing.

What laboratory tests can help detect myelofibrosis?

Blood work often plays a key role in identifying abnormalities associated with myelofibrosis. Common tests include:

• Complete blood count (CBC) – Measures the levels of red blood cells, white blood cells and platelets to identify anemia and other blood count abnormalities
• Peripheral blood smear – Examines a blood sample under a microscope to evaluate the size, shape and maturity of blood cells
• Genetic testing for JAK2, CALR and MPL mutations – Detects gene changes commonly associated with myelofibrosis and helps confirm the diagnosis
• Inflammatory marker tests – Measure substances in the blood that indicate inflammation, which may be elevated in people with myelofibrosis

What imaging tests are used to evaluate myelofibrosis?

Imaging may be used to check for organ involvement, particularly spleen enlargement. Commonly used imaging tests include:

• Ultrasound – Uses sound waves to create images of internal organs, such as the spleen, to measure size and monitor enlargement
• Computed tomography (CT) scans – Use X-rays and computer technology to produce detailed cross-sectional images of structures inside the body, such as the spleen, liver and other abdominal organs, to evaluate size and condition
• Magnetic resonance imaging (MRI) – Uses magnetic fields and radio waves to create high-definition images of the internal anatomy, which may be used in select cases to assess bone marrow changes

What procedures are used to diagnose myelofibrosis?

A definitive diagnosis of myelofibrosis requires direct microscopic examination of a bone marrow sample. Diagnostic procedures may include:

• Bone marrow biopsy – Removes a small core of bone tissue and marrow, usually from the hip bone, to evaluate the structure of the marrow and check for scarring and abnormal cells
• Bone marrow aspiration – Removes a small amount of liquid bone marrow to examine blood-forming cells, detect genetic mutations and assess how well the marrow is producing blood cells

How is myelofibrosis treated?

Treatment for myelofibrosis is highly individualized based on the patient’s age, symptoms, risk profile and overall health. Some people may not need immediate treatment, while others can benefit from early intervention.

Targeted therapy for myelofibrosis

Targeted therapy is a cornerstone of myelofibrosis treatment, which primarily focuses on symptom management. This approach uses Janus kinase (JAK) inhibitors to block overactive JAK signaling, which can reduce spleen size and improve symptoms such as night sweats, bone pain and itching. Common targeted drugs include ruxolitinib, fedratinib and momelotinib. Possible side effects of targeted therapy for myelofibrosis include anemia, low platelets and increased risk of infection.

Bone marrow transplantation for myelofibrosis

The only potentially curative treatment for myelofibrosis is an allogeneic stem cell transplant, which replaces diseased bone marrow with healthy blood-forming cells from a donor. Because this intensive treatment carries significant risks, such as graft-versus-host disease (GVHD), serious infections and organ complications, it is generally reserved for select patients. Eligibility depends on the patient’s age, risk profile and overall health.

Surgery for myelofibrosis

Although surgery is not a standard treatment for myelofibrosis, it may be considered in certain cases. For example, a splenectomy may be recommended to remove an enlarged spleen that is causing severe symptoms that do not respond to conservative therapies.

Chemotherapy for myelofibrosis

Chemotherapy may be used to control abnormal blood cell production or manage disease progression. Common chemotherapy drugs include:

• Hydroxyurea
• Low-dose cytarabine

Possible side effects of chemotherapy for myelofibrosis include fatigue, increased risk of infection and low blood cell counts.

Radiation therapy for myelofibrosis

Radiation therapy may be used to shrink an enlarged spleen or relieve bone pain if other treatments are ineffective. Possible side effects include fatigue and temporary blood count suppression.

Benefit from world-class care at Moffitt Cancer Center

Moffitt is a nationally recognized leader in treating blood cancers and myeloproliferative neoplasms. Our patients benefit from multispecialty expertise, access to leading-edge clinical trials and individualized treatment plans grounded in the latest research. At Moffitt, care is focused not only on treating cancer but on supporting the whole person throughout every stage of their journey.

If you would like to learn more about myelofibrosis, you can request an appointment with a specialist in the Malignant Hematology Program at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.