What is Myelofibrosis? Symptoms to Know

Myelofibrosis is a rare blood cancer that belongs to a group of disorders called myeloproliferative neoplasms. It is a type of bone marrow cancer or chronic leukemia in which the bone marrow makes too many abnormal blood cells. (The bone marrow is the soft, spongy tissue inside bones where the production of blood cells from stem cells (immature blood cells) takes place).

In myelofibrosis patients, the large number of cancer cells in the bone marrow leads to the replacement of the soft, spongy tissue with fibrous scar tissue. The abnormal cancer cells and the scarring in the diseased bone marrow prevent it from making healthy blood cells, including red blood cells that carry oxygen to the body’s tissues, white blood cells that help the immune system fight infections, and platelets that help blood clot.

The bone marrow scarring, the presence of abnormal cells, and the lack of enough normal blood cells cause the symptoms of myelofibrosis, such as severe anemia, an enlarged spleen, and frequent infections. Please continue reading to learn more about myelofibrosis.

What causes myelofibrosis?

Myelofibrosis can happen on its own without other blood cancers (this is called primary myelofibrosis or chronic idiopathic myelofibrosis). It can also develop from other bone marrow disorders, such as polycythemia vera or essential thrombocytopenia, called secondary myelofibrosis).

The exact cause of myelofibrosis is unclear, but it is linked to mutations (changes or defects) in certain genes. Approximately 60% of people with myelofibrosis have a mutation in the JAK2 gene, which is responsible for the formation of proteins called janus-associated kinases (JAKs). JAKs play an important role in blood cell production in the bone marrow. When these proteins become overactive due to a mutation in the JAK2 gene, it results in a blood cell disorder with abnormal growth of blood-forming cells and bone marrow fibrosis. Genetic mutations in other genes, such as the myeloproliferative leukemia (MPL) gene and calreticulin (CALR) gene, have also been linked to abnormalities in developing blood cells and myelofibrosis.

Risk factors for myelofibrosis include age over 50 and other blood disorders such as thrombocytopenia and polycythemia vera. In addition, people exposed to ionizing radiation or harmful chemicals such as toluene or benzene are at an increased risk.

What is one important clinical finding in primary myelofibrosis?

There are several important clinical findings in primary myelofibrosis. The production of abnormal blood cells and bone marrow scarring cause the following clinical signs in myelofibrosis patients:

Anemia: The decreased red blood cell production in the diseased bone marrow leads to anemia and reduced transport of oxygen to the body’s tissues.
Thrombocytopenia: The decreased platelet formation increases the risk of bruising, easy bleeding, and bleeding complications.
Splenomegaly: The increased workload on the spleen to remove damaged red blood cells from the circulation leads to an enlarged spleen.
Extramedullary hematopoiesis: People with myelofibrosis develop abnormal growths of blood-forming tissues outside the bone marrow, such as in the lymph nodes, gastrointestinal tract, lungs, spinal cord, and brain. These abnormal blood cells impair the functioning of the affected organs and form tumors that press upon surrounding structures, causing symptoms. For example, extramedullary hematopoiesis can lead to portal hypertension (increased blood pressure in a vein in the liver).
Acute leukemia: Around 10-12% of people with primary myelofibrosis develop an aggressive form of leukemia called acute myeloid leukemia as the disease progresses.

How do you feel with myelofibrosis?

People with myelofibrosis experience fatigue, fever, night sweats, pale skin, itching, weight loss, bone pain, joint pain, and frequent infections.

These symptoms of myelofibrosis develop because scar tissue builds in the bone marrow, where the body makes blood cells. This affects how many blood cells are made and causes symptoms.

For example, when scar tissue forms, it leads to a low number of healthy red blood cells (anemia) and causes symptoms such as fatigue, weakness, pale skin, and shortness of breath. A low platelet count (thrombocytopenia) can lead to an unexplained blood clot, easy bruising, and abnormal bleeding. A lack of healthy cells that fight infections can lead to an increased susceptibility to infections. An enlarged spleen can cause fullness in the left upper abdomen.

How long can you have myelofibrosis without knowing?

Myelofibrosis develops slowly, and many people with this condition do not have any symptoms for years. However, the condition can get progressively worse and require treatment for MF symptoms. If you have received a diagnosis of myelofibrosis, you will need regular follow-ups with your healthcare providers, even if you are symptom-free.

How do doctors diagnose myelofibrosis?

Doctors diagnose myelofibrosis based on the medical history, symptoms, physical exam, blood tests (complete blood count, peripheral blood smear, blood chemistries), and imaging studies. A confirmed diagnosis can be made with bone marrow tests (bone marrow aspiration or bone marrow biopsy) in which a small sample of bone marrow tissue is removed and examined under a microscope to look for evidence of scar tissue. Additionally, tests for gene mutations in JAK2, MPL, and CALR genes may be done to make a diagnosis of myelofibrosis.

What is the treatment for myelofibrosis?

You may not need treatment for myelofibrosis if you don’t have any symptoms. If you have symptoms, your healthcare providers will develop a treatment plan to relieve your symptoms and reduce your risk of complications. Treatment options for people with myelofibrosis include:

Blood transfusions.
Chemotherapy drugs and radiation.
Splenectomy (surgical removal of the spleen).
Medications to treat anemia.
JAK inhibitors such as ruxolitinib (Jakafi), fedratinib (Inrebic), and pacritinib (Vonjo). These are US Food and Drug Administration (FDA) approved drugs to treat moderate to high-risk myelofibrosis. They work by reducing overactive JAK proteins and can provide relief from myelofibrosis symptoms such as fever, night sweats, itching, weight loss, and spleen enlargement.
Allogeneic stem cell transplants. This is the only potential cure for myelofibrosis. It involves destroying your stem cells (blood-forming cells) with chemotherapy or high doses of radiation and replacing them with healthy stem cells from a donor. However, not everyone with myelofibrosis is a candidate for stem cell transplant, which is a high-risk treatment.

What are the signs that myelofibrosis is progressing?

Progression of myelofibrosis is marked by increasing signs and symptoms due to a falling number of blood cells (white blood cells, red blood cells, and platelets) as well as worsening clinical and laboratory parameters.

The average survival after myelofibrosis cancer diagnosis is 6 years, but it can vary widely depending on the severity of the disease and ranges from 2 to 15 years or even longer.

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