What Is Myelofibrosis?

Myelofibrosis is a rare type of bone marrow cancer. In this condition, extensive scarring (fibrosis) occurs in the bone marrow, which keeps the bone marrow from producing the right number of blood cells.

Healthy functioning bone marrow produces infection-fighting white blood cells (WBCs), oxygen-carrying red blood cells (RBCs), and blood-clotting platelets in the correct numbers the body needs to function normally.

When myelofibrosis occurs, some people may not have any symptoms, while others have severe symptoms that require immediate treatment. This article will explain the symptoms of myelofibrosis, how it is diagnosed, and how it is treated. 

How Myelofibrosis Affects the Body

Bone marrow is present inside the middle of the bones. It is normally a soft, spongy texture. It produces WBCs, RBCs, and platelets.

In myelofibrosis, one of the cells of the bone marrow begins to grow abnormally, multiply, and continue to produce more abnormal cells. Eventually, abnormal cells are present in high enough numbers to crowd out the healthy cells.

These abnormal cells cause fibrosis, which prevents the bone marrow from producing the correct number of blood cells the body needs to function normally. Over time, there is an increased risk of developing acute myeloid leukemia (AML), another form of blood cancer.

Myelofibrosis Types

The initial cause of abnormal bone marrow development determines the type of myelofibrosis. The two types are primary and secondary.

Primary Myelofibrosis

With primary myelofibrosis, the change in the bone marrow cells happens spontaneously. It doesn’t occur due to a previous bone marrow condition.

Secondary Myelofibrosis

With secondary myelofibrosis, the fibrosis occurs due to another bone marrow disorder, specifically polycythemia vera or essential thrombocythemia.

Polycythemia vera is a blood disorder in which the bone marrow produces too many blood cells, most often red blood cells, but can also include white blood cells and platelets. Essential thrombocythemia is a disorder in which the bone marrow makes too many platelets.

Myelofibrosis Symptoms

As too few blood cells are made, symptoms will start to develop. The rate at which symptoms develop and how severe they become can vary from person to person, and may take years to be experienced. Symptoms associated with myelofibrosis include:

• Feeling tired
• Shortness of breath
• Pale skin
• Headaches
• Fever
• Night sweats
• Enlarged spleen
• Enlarged liver
• Frequent infections
• Easy bleeding or bruising
• Abdominal pain
• Joint pain
• Bone pain

Tumors may develop in the lungs, skin, liver, or gastrointestinal tract and cause further symptoms.

Causes of Myelofibrosis

For those living with primary myelofibrosis, the exact cause of the disease may never be known.

However, in about half of the cases of primary myelofibrosis, a mutation in the JAK2 gene is found. The JAK2 mutation is also frequently found in those with polycythemia vera and essential thrombocythemia.

This mutation isn't inherited. Instead, it develops spontaneously in a bone marrow cell. It produces a protein that causes the bone marrow to overproduce platelet precursor cells called megakaryocytes. These cells stimulate other cells to produce too much collagen, a protein that then builds up and produces scarring in the bone marrow.

Other gene mutations that may play a role in developing myelofibrosis include the CALR and MPL genes. 

Risk factors that may play a role in developing primary myelofibrosis include:

• Increasing age
• History of exposure to chemicals including benzene, fluoride, or phosphorus

Risk factors for developing secondary myelofibrosis include:

• Having another cancer that has spread into the bone marrow
• Having polycythemia vera or essential thrombocythemia

Diagnosis of Myelofibrosis

The diagnosis of myelofibrosis often starts when someone presents to their healthcare provider for evaluation of a symptom that they are experiencing. During this evaluation, a healthcare provider may start with a detailed history and physical examination. Blood work may be taken which can start the process of finding a diagnosis.

A complete blood count (CBC) and peripheral blood smear measure the number of WBCs, RBCs, and platelets, as well as their shape and size. Abnormal findings in the CBC may lead to further testing, which may include a bone marrow biopsy.

During a bone marrow biopsy, a small sample of bone marrow is taken, often from the hip. This allows the pathologist (physician specializing in analyzing body fluids and tissues in a lab setting) the ability to evaluate for any changes or abnormalities in the bone marrow. This test can result in a diagnosis of myelofibrosis. 

In addition, a physical exam or imaging study such as a computed tomography (CT) scan may reveal an enlarged spleen.

Other blood testing may include:

• Complete metabolic panel (CMP) to evaluate kidney and liver function
• Coagulation studies
• Iron levels
• Lactate dehydrogenase (LDH) to assess inflammation and tissue damage
• Testing for the JAK2, CALR, and MPL gene mutations

Once a diagnosis of myelofibrosis is made, it is further classified into different risk categories, which helps determine how likely the disease is to turn into AML and can help determine treatment options.

This score is determined by the person's age, symptoms, hemoglobin level, platelet count, leukocyte (a white blood cell) and leukoblast (a developing white blood cell) count, and certain genetic changes. The higher the score, the more high-risk their myelofibrosis is. 

Myelofibrosis Treatment

Some people diagnosed with myelofibrosis, especially those without many symptoms or who have low-risk disease, may not receive any treatment until they become symptomatic. Called a watchful waiting approach, this policy of taking no immediate action regarding treatment includes routine blood tests and visits with their healthcare provider to determine when treatment will be needed.

If someone is experiencing symptomatic anemia (low RBCs) because of myelofibrosis, they may receive periodic RBC transfusions. There are additional medications that may be given to help the bone marrow make red blood cells.

This may not completely resolve anemia but can keep the red blood cells up at a tolerable level. If someone also has iron deficiency anemia, iron supplements may help improve red blood cell levels.

To reduce high levels of WBCs and platelets, medications to suppress the bone marrow may be given. An example of one of these medications is hydroxyurea. 

An enlarged spleen may need to be treated if it is contributing to symptoms, especially pain or severely low platelets. This can be done through radiation to the spleen or by surgical removal of the spleen.

A medication called Jakafi (ruxolitinib) can be prescribed to those with either primary or secondary myelofibrosis who fall in the moderate- or high-risk category. This medication interferes with the JAK2 pathway that the cells use to grow. Other medications include Inrebic (fedratinib) and Ojjaara (momelotinib), which can also be used to treat intermediate or high-risk adults with myelofibrosis.

Can Myelofibrosis Be Cured?

The majority of cases of myelofibrosis are treated with the goal of decreasing symptoms of the disease. An attempt can be made to cure the disease through a stem cell transplant.

This approach requires large doses of chemotherapy to kill all of the cancer cells. Stem cells are collected before the procedure to be infused back in after chemotherapy has worked. These stem cells can then begin to resume making normal WBCs, RBCs, and platelets. This procedure is not recommended for everyone with myelofibrosis, as it can lead to severe complications.

Complications Associated With Myelofibrosis

Complications associated with myelofibrosis are related to the severe decrease in the number of normal WBCs, RBCs, and platelets. As the disease progresses and the blood counts continue to decrease, complications may arise. 

With the decrease of white blood cells comes a higher risk of developing infection. Infections can occur anywhere in the body, though most often in the lungs. The infection can be due to bacteria, viruses, or fungi. With infection may come fever, increased weakness, and cough.

Low red blood cells can result in severe anemia, which prevents enough oxygen-rich blood from getting to the tissues in the body. With the decreased amount of available oxygen comes complications such as heart failure, in which the heart has to work too hard to try to keep up with the increased demand for oxygen. 

Not having enough normal platelets can lead to severe bleeding or hemorrhaging. The bleeding can occur following an injury or can occur spontaneously. The bleeding can become life-threatening if severe and not stopped quickly.

Blood clotting, the opposite of bleeding, could also occur. If blood clots inappropriately, it can lead to clots moving around the body and getting stuck in areas they are not supposed to be. This can lead to damage to the brain, heart, lungs, and extremities. 

Transformation to acute myeloid leukemia occurs in 5% to 10% of those diagnosed with myelofibrosis. This is most common in primary myelofibrosis and is a significant complication since the prognosis is poor with transformation into AML.

Myelofibrosis Prognosis

The prognosis of myelofibrosis can vary from person to person. It depends upon the type and risk category of their disease. Prognosis can differ slightly based on which scale is used at the time of diagnosis. The table below references the prognosis scale MIPSS70, which is used for those 70 years old or younger and is based on risk group severity.

When to Contact a Healthcare Provider

See a healthcare provider if you are having symptoms associated with myelofibrosis. Many of these are also associated with other conditions. A workup and diagnosis can ensure you are getting the appropriate treatment.

If you have been diagnosed with myelofibrosis, contact your healthcare provider anytime you’re having concerns about the symptoms you’re experiencing, especially if they continue for some time without getting better.

Your provider may want to run additional tests or start treatment if your symptoms continue. If severe symptoms develop, notify your healthcare provider immediately or seek emergency care. 

Summary

Myelofibrosis is a type of blood cancer in which abnormal cells cause the bone marrow to become extensively scarred (fibrosis). The fibrosis doesn't allow the bone marrow to make blood cells properly, which leads to low blood counts and other complications.

Once formally diagnosed by a bone marrow biopsy, the results will be used by your healthcare provider to develop a treatment plan. Treatments are individualized, ranging from watchful waiting to stem cell transplant.