Myelofibrosis

What is myelofibrosis?

Myelofibrosis is a rare type of blood cancer where your bone marrow (the soft, spongy tissue inside of your bones) is replaced by fibrous scar tissue. It’s a form of chronic leukemia and a myeloproliferative disorder. Myeloproliferative disorders involve too many blood cells getting made in your bone marrow — where blood cells get made.

Your bone marrow produces immature blood-forming cells called stem cells that may develop into red blood cells, white blood cells or platelets. With myelofibrosis, a change (mutation) in a stem cell’s DNA causes the cell to become defective, or a cancer cell, instead. The cell multiplies, passing the mutation onto new cells.

Over time, more abnormal cancer cells are produced. Some of these cells create inflammation that causes scar tissue to form in your bone marrow. The scarring and the excess cancer cells can prevent your bone marrow from making healthy blood cells.

What are the types of myelofibrosis?

There are two types of myelofibrosis:

• Primary myelofibrosis is myelofibrosis that occurs on its own.
• Secondary myelofibrosis arises secondary to other blood disorders, including primary thrombocytosis or polycythemia vera. Secondary myelofibrosis accounts for about 10% to 20% of diagnoses.

How common is myelofibrosis?

Myelofibrosis is rare, with about 1.5 cases reported per 100,000 people each year in the United States. It affects people regardless of sex. People of any age can have myelofibrosis, although it’s more likely to be diagnosed in people over 50. Children with myelofibrosis are usually diagnosed before age 3.

How does myelofibrosis affect my body?

The abnormal blood cell production can lead to a variety of conditions, including:

• Anemia: A deficiency of red blood cells. Your red blood cells help transport oxygen throughout your body. Too few red blood cells deprive your tissues of oxygen, causing symptoms like fatigue, weakness and shortness of breath.
• Thrombocytopenia: A deficiency of platelets. Platelets help your blood clot when you’re injured. A low platelet count may make you more susceptible to bleeding and bruising.
• Splenomegaly: An enlarged spleen. Your spleen controls your number of blood cells and removes damaged red blood cells from your body. Too many abnormal blood cells can overwork your spleen, causing it to enlarge. Splenomegaly may feel like a sensation of fullness or discomfort in the upper left section of your abdomen.
• Extramedullary hematopoiesis: Abnormal growth of blood-forming cells outside of your bone marrow. These cells may grow in other body parts, such as your lungs, gastrointestinal tract, spinal cord, brain or lymph nodes. The cells can form masses (tumors) that press on organs or impair their function.
• Portal hypertension: An increase in blood pressure in the vein that carries blood from your spleen to your liver. It likely results from damage to your veins related to extramedullary hematopoiesis.

In about 12% of all cases, primary myelofibrosis progresses to acute myeloid leukemia, a very aggressive form of blood cancer.

What causes myelofibrosis?

Scientists don’t know what causes myelofibrosis, but they know it’s associated with DNA changes in specific genes. Proteins called Janus-associated kinases (JAKs) play a role in myelofibrosis. JAKs regulate the production of blood cells in bone marrow by signaling the cells to divide and grow. If the JAKs become overactive, too many or too few blood cells will be produced.

About 60% to 65 % of people with myelofibrosis have a mutation in the JAK2 gene. Another 5% to 10% have a mutation in the myeloproliferative leukemia (MPL) gene. A mutation called calreticulin (CALR) accounts for approximately 20% to 25 % of myelofibrosis cases.

What are the risk factors for myelofibrosis?

You’re at increased risk of myelofibrosis if:

• You’re over 50.
• You have primary thrombocytosis or polycythemia vera.
• You’ve been exposed to ionizing radiation or petrochemicals like benzene or toluene.

What are the symptoms of myelofibrosis?

Myelofibrosis progresses slowly, so you may not have symptoms for many years. About one-third of people don’t show symptoms during the disorder’s early stages.

When they arise, the most common symptoms of myelofibrosis are severe fatigue (resulting from anemia) and an enlarged spleen. Symptoms may include:

• Fatigue.
• Fever.
• Itching.
• Pale skin.
• Weight loss.
• Night sweats.
• Bone or joint pain.
• Frequent infections.
• Enlarged spleen or liver.
• Unexplained blood clots.
• Abnormal bleeding or bruising.
• Enlarged veins in your stomach and esophagus. (These veins may rupture and cause bleeding.)

How is myelofibrosis diagnosed?

A healthcare provider (oncologist) will perform a physical exam and ask about your medical history, including any symptoms you’re experiencing. They’ll check for signs of an enlarged spleen and anemia.

They’ll perform various tests to rule out other conditions and confirm your diagnosis.

Blood tests

• Complete blood count (CBC): This test measures your number of blood cells. A lower than normal number of red blood cells and abnormal amounts of white blood cells and platelets may suggest myelofibrosis.
• Peripheral blood smear (PBS): This test shows if your blood cells are abnormal in size, shape or other features. Abnormal-looking cells and large numbers of immature blood cells may be a sign of myelofibrosis.
• Blood chemistry tests: These tests measure levels of various substances your organs release into your blood. They can show how an organ is functioning. High levels of uric acid, bilirubin and lactic dehydrogenase may signal myelofibrosis.

Bone marrow tests

• Bone marrow biopsy: This test removes a sample of bone marrow that your provider examines underneath a microscope. They’ll analyze the cells to confirm you have myelofibrosis.
• Bone marrow aspiration: This test removes the fluid part of bone marrow so your provider can examine it for signs of myelofibrosis.

You may need additional tests to confirm your diagnosis, including:

• Gene mutation analysis: Your healthcare provider will examine blood and bone marrow cells to check for the genetic mutations associated with myelofibrosis, including JAK2, CALR and MPL. Certain treatments target cancer cells with JAK2 mutations.
• Imaging procedures: Your provider may perform an ultrasound to check for an enlarged spleen. They may perform an MRI to check for scar tissue in your bone marrow that may be a sign of myelofibrosis.

How is myelofibrosis treated?

You don’t need treatment unless you’re experiencing symptoms. Still, your healthcare provider will monitor your condition even if you don’t require immediate treatment.

Jakafi® (ruxolitinib), Inrebic® (fedratinib) and Vonjo® (pacritinib) are U.S. Food and Drug Administration (FDA)-approved drugs for treating intermediate or high-risk myelofibrosis. All three drugs are JAK inhibitors that reduce overactive Janus-associated kinase (JAK) signaling. They help relieve some of the symptoms associated with myelofibrosis, including an enlarged spleen, night sweats, itching, weight loss and fever.

For most people, treatment goals are to manage conditions associated with myelofibrosis, including anemia and splenomegaly.

Anemia treatments

Treatments for anemia include:

• Androgens: Taking androgens, like danazol, can boost red blood cell production.
• Immunomodulators: Taking immunomodulators can boost your immune system’s ability to fight cancer cells, reducing symptoms. Medications include interferon, thalidomide (Thalomid®) and lenalidomide (Revlimid®). They may be prescribed along with glucocorticoids, like prednisone.
• Chemotherapy drugs: Taking certain chemotherapy drugs can lessen symptoms related to high blood counts and splenomegaly. Medications include hydroxyurea and cladribine.
• Blood transfusions: Receiving regular blood transfusionscan increase your red blood cell count if you have severe anemia.

Splenomegaly treatments

Treatments used to manage an enlarged spleen include JAK inhibitors, immunomodulators and chemotherapy drugs. In severe cases, you may need to have your spleen removed (splenectomy), or you may need radiation therapy to your spleen.

You may need radiation therapy to treat extramedullary hematopoiesis (abnormal growth of stem cells outside of your bone marrow).

Can myelofibrosis be cured?

Allogeneic hematopoietic cell transplantation (HCT) is a potential cure, but it’s a risky procedure that may not be an option for everyone.

The procedure involves replacing abnormal blood cells with healthy cells from a donor. Before the transplant, you’ll receive chemotherapy or radiation therapy to destroy your diseased cells so the new cells from the donor will take over.

HCT carries a high risk of complications and is only suitable for certain people. The risk of a complication is higher for people with other medical conditions. Various factors will determine whether you’re a candidate, including your age, the severity of your symptoms and your likelihood of success.

What is the life expectancy for someone with myelofibrosis?

Myelofibrosis is aggressive cancer with a median survival rate of six years. A median is a midpoint, which means that some people live less than six years, and about the same number of people live longer than six years.

Multiple factors affect your prognosis, including:

• Your age.
• Your symptoms.
• Your number of blood cells.
• The severity of the scarring in your bone marrow.
• The presence of genetic mutations (JAK2, CALR, MPL).

Talk with your provider about what your diagnosis means for your experience of the disease.

How do I take care of myself?

Ask your healthcare provider if you could benefit from palliative care. Palliative care teams may include doctors, nurses, social workers and other care specialists who provide resources to help you navigate your illness. They provide a support network that complements the care you receive from your oncologist. Palliative care specialists can improve your quality of life as someone navigating a cancer diagnosis.