What Is Myelofibrosis?

Myelofibrosis, also known as agnogenic myeloid metaplasia, is a rare disease that causes progressive scarring (fibrosis) of bone marrow, leading to abnormal blood cell counts and other serious complications. Some people with the disease may not have symptoms or require immediate treatment. Others have aggressive disease and develop severe anemia, liver dysfunction, and spleen enlargement. Myelofibrosis can be diagnosed with blood tests and a bone marrow biopsy. The only known cure is a stem cell transplant. 

Types of Myelofibrosis

Myelofibrosis is classified as a myeloproliferative neoplasm, a group of disorders characterized by the overproduction of at least one type of blood cell. Neoplasm refers to abnormal, excessive growth of tissues characteristic of both cancerous and benign tumors.

Myelofibrosis is a complex disease that can either be classified as a primary or secondary neoplasm.

• Primary myelofibrosis is a form of the disease that develops spontaneously in the bone marrow. It is often referred to as primary idiopathic myelofibrosis (idiopathic means "of unknown origin").
• Secondary myelofibrosis is the type in which changes in bone marrow are triggered by another disease or condition. As such, myelofibrosis is considered secondary to a primary cause.

Symptoms

Myelofibrosis causes progressive failure of the bone marrow, impairing its ability to produce the red blood cells (responsible for transporting oxygen to and removing waste from the body), white blood cells (responsible for immune defense), and platelets (responsible for clotting).

When this occurs, blood-forming cells in other organs of the body are forced to take over, placing excessive strain on organs and causing them to swell.

Common symptoms of myelofibrosis include:

• Fatigue and weakness
• Shortness of breath
• An unhealthy pale appearance
• Abdominal swelling and tenderness
• Bone pain
• Easy bruising and bleeding
• Loss of appetite and weight
• Increased risk of infection, including pneumonia
• Skin nodules (cutaneous myelofibrosis)
• Gout

Complications

As the disease progresses and begins to affect multiple organs, it can lead to serious complications, among them:

• Bleeding complications, including esophageal varices
• Formation of tumors outside of the bone marrow
• Portal hypertension (increased blood pressure within the liver)
• Acute myeloid leukemia (AML)

Causes

Myelofibrosis is associated with genetic mutations in hemopoietic (blood-forming) cells in the bone marrow. Why these mutations occur isn't fully understood, but when they do, they can be passed to new blood cells. Over time, the proliferation of mutated cells can overtake the bone marrow's ability to produce healthy blood cells.

The mutations most closely linked to myelofibrosis include the JAK2, CALR, or MPL gene. Around 90% of cases involve at least one of these mutations, while 10% carry none of these mutations.

Risk Factors

Known risk factors associated with both primary and secondary myelofibrosis, include:

• A family history of myeloproliferative disease
• Jewish descent
• Older age
• Certain autoimmune conditions, especially Crohn's disease

Secondary myelofibrosis is further linked to other diseases or conditions that directly or indirectly affect the bone marrow, including:

• Metastatic cancers (cancers that spread from other parts of the body to the bone marrow)
• Polycythemia vera (a type of blood cancer that causes the overproduction of blood cells)
• Hodgkin and non-Hodgkin lymphoma (cancers of the lymphatic system)
• Multiple myelomas (blood cancers affecting plasma cells)
• Acute leukemia (a blood cancer affecting leukocytes)
• Chronic myeloid leukemia (cancer of the bone marrow)
• Exposure to certain chemicals, such as benzene or petroleum
• Radiation exposure

Diagnosis

If your healthcare provider suspects you may have myelofibrosis, the diagnosis will typically start with a review of your medical history (including risk factors) and a physical exam to check for liver or spleen enlargement or abnormal skin nodules.

Blood and imaging tests will likely be the next steps toward diagnosing myelofibrosis. The blood test panel is likely to include:

• Complete blood count (CBC), to establish if blood cell types are high or low
• Peripheral blood smear, to look for abnormally-shaped blood cells
• Genetic tests, to check for characteristic gene mutations

Imaging tests, such as X-ray, computed tomography (CT), or magnetic resonance imaging (MRI), can help detect organ enlargement, vascular distension, or abnormal hardening of the bone (osteosclerosis) common with myelofibrosis.

A bone marrow biopsy is routinely used to identify characteristic changes in the bone marrow and help stage the disease. It involves the insertion of a long needle into the center of the bone to extract a sample of bone marrow. A bone marrow biopsy is a moderately invasive procedure that can be performed on an outpatient basis under local anesthesia.

Differential Diagnoses

In order to ensure the correct diagnosis, the healthcare provider would exclude other possible causes for your symptoms (referred to as a differential diagnosis). Chief among these are other classical chronic myeloproliferative neoplasms, including:

• Chronic myeloid leukemia
• Polycythemia vera
• Essential thrombocythemia
• Chronic neutrophilic leukemia
• Chronic eosinophilic leukemia

Being diagnosed with these diseases doesn't necessarily mean that myelofibrosis isn't involved. In some cases, myelofibrosis may be secondary to the related disease, most especially with polycythemia vera and essential thrombocythemia.

Treatment

This primarily focuses on symptom relief, improving blood cell counts, and preventing complications. The potential cure for myelofirosis is a bone marrow/stem cell transplant.

Treatment decisions are ultimately guided by:

• Whether or not you have symptoms
• Your age and overall health
• The risks involved with your specific case

If you are symptomatic, the focus would be placed on treating severe anemia and splenomegaly. If your symptoms are severe, a bone marrow transplant may be advised.

Anemia Treatment

Anemia is a condition in which you lack enough healthy red blood cells to carry adequate oxygen to the body's tissues. It is one of the most common features of myelofibrosis and one that can be treated or prevented with the following interventions:

• Blood transfusions are used to treat severe anemia and are often given periodically to people with severe myelofibrosis. Anti-anemia drugs like Epogen (epoetin alfa) may be prescribed if the kidney is involved. An iron-rich diet along with iron, folate, and vitamin B12 supplements may also help.
• Androgen therapy involves the injection of synthetic male hormones like Danocrine (danazol) to stimulate red blood cell production. Androgen therapy may cause masculinizing effects in women and increase the risk of liver damage with long-term use.
• Glucocorticoids are types of steroid drugs that reduce systemic inflammation and may improve red blood cells counts. Prednisone is the most commonly prescribed steroid but it should be noted that using it long term may cause cataracts and an increased risk of infection.
• Immune-modulating drugs like Thalomid (thalidomide), Revlimid (lenalidomide), and Pomalyst (pomalidomide) can help increase red blood cell counts while reducing spleen enlargement.

Splenomegaly Treatment

With myelofibrosis, the spleen is the organ most affected by bone marrow failure since it has a high concentration of hemopoietic cells. There are several options used to treat myelofibrosis-associated splenomegaly:

• Chemotherapy drugs, such as hydroxyurea and cladribine, are often used in the first-line treatment of splenomegaly to reduce swelling and pain.
• Jakafi (ruxolitinib) is a chemotherapy drug that targets the JAKS mutations most commonly associated with myelofibrosis. Jakafi may cause nausea, diarrhea, liver inflammation, reduced platelets, and increased cholesterol in some.
• Splenectomy, the surgical removal of the spleen, may be recommended if the spleen becomes so large as to cause pain and increase the risk of complications. While there are risks associated with any surgery, a splenectomy usually does not affect life span or quality of life.
• Radiation therapy may be considered if a splenectomy is not an option. Side effects may include nausea, diarrhea, fatigue, loss of appetite, skin rash, and hair loss (usually temporary).

Stem Cell Transplant

A bone marrow transplant, also known as a stem cell transplant, is a procedure used to replace diseased bone marrow with stem cells from the healthy bone. For myelofibrosis, the procedure is called allogeneic stem cell transplant (meaning that a donor is required).

A bone marrow transplant has the potential to cure myelofibrosis but also carries a high risk of life-threatening side effects. This includes graft-versus-host disease in which the transplant cells attack healthy tissues.

Prior to the transplant, you will undergo conditioning treatment (involving either chemotherapy or radiation therapy) to destroy all diseased bone marrow. You will then receive an intravenous (IV) infusion of stem cells from a compatible donor. The conditioning helps reduce the risk of rejection by suppressing the immune system but also places you at a high risk of infection.

Because of these risks, an extensive evaluation is needed to determine whether you are a good candidate for a stem cell transplant.

Prognosis

Based on the current body of evidence, the median survival time for people with myelofibrosis is 3.5 years to 5.5 years from the time of diagnosis. This doesn't mean, however, that you can only have only three to five years to live if diagnosed with myelofibrosis.

Among the other factors that can increase survival times are:

• Being under 65 at the time of diagnosis
• Hemoglobin counts greater than 10 grams per deciliter (g/dL)
• White blood cell count of less than 30,000 per microliter (mL)

The severity of symptoms (including spleen enlargement, fever, night sweats, and weight loss) also plays a role in survival times.

Coping

Living with any potentially life-threatening disease can be stressful. If you or a loved one is diagnosed with myelofibrosis, the best way to cope and support the recommended treatment is to remain healthy.

The MPN Coalition, a non-profit organization supporting people with myeloproliferative neoplasms, recommends eating a healthy Mediterranean diet. This includes replacing butter with healthy oils and limiting red meat to once or twice monthly.

Because myelofibrosis can weaken the immune system, it is important to avoid infection by:

• Washing your hands regularly
• Avoiding anyone with cold, flu, or other communicable illnesses
• Washing fruits and vegetable
• Avoiding raw meat, fish, eggs, or unpasteurized milk

It is also important to find support from family, friends, and your medical team and to seek help from a therapist or psychiatrist if you experienced deep depression or anxiety. Regular exercise also helps lift moods and improves sleep in addition to its physical benefits.

It also helps to reach out to support groups to connect with others living with myelofibrosis who can offer support, tips, and professional referrals. Online support groups can be found on Facebook and through the non-profit MPN Research Foundation.

A Word From Verywell

So far, the survival time of people with primary myelofibrosis appears more closely related to their symptoms and blood abnormalities than any one treatment or treatment approach.

As such, the disease needs to be treated on an individualized basis, weighing the potential benefits and risks through every stage of the disease. If you are uncertain about a recommended treatment or don't think you're being treated aggressively enough, do not hesitate to seek a second opinion from a qualified hematologist or oncologist specializing in myeloproliferative neoplasms.