Myelofibrosis

How myelofibrosis develops

Myelofibrosis begins with an acquired mutation in a blood-forming stem cell, most often in the JAK2, CALR or MPL gene. These mutations switch on growth signaling. Abnormal megakaryocytes (platelet-forming cells) release chemicals that cause scar tissue to build up in the marrow and drive inflammation. As the marrow fails, the spleen and liver try to take over blood production (extramedullary hematopoiesis), causing them to enlarge.

These mutations are acquired during life, not inherited.

Types

• primary myelofibrosis: arises on its own
• secondary myelofibrosis: develops after years of polycythemia vera or essential thrombocythemia
• prefibrotic myelofibrosis: an early stage with less scarring, often mistaken for essential thrombocythemia

Symptoms

• fatigue and breathlessness from anemia
• enlarged spleen: fullness, early satiety, left-sided belly pain
• night sweats, fevers and weight loss
• itching, especially after a hot shower
• bone and joint pain
• easy bruising or bleeding, or frequent infections
• gout from high uric acid

Some people have no symptoms at diagnosis and are found through routine blood tests.

Diagnosis

• Full blood count: anemia; white cells and platelets may be high or low
• Blood film: teardrop-shaped red cells and immature white and red cells (leukoerythroblastic picture)
• Bone marrow biopsy: shows fibrosis and abnormal megakaryocytes; marrow aspiration is often a "dry tap"
• Mutation testing: JAK2, CALR, MPL and additional high-risk mutations
• Imaging: ultrasound or MRI to measure spleen size
• LDH and uric acid

Risk scoring

Scores such as DIPSS-plus and MIPSS70 use age, blood counts, symptoms and genetics to predict outlook and guide treatment, especially the decision about transplant.

Treatment

Observation

People with low-risk disease and no symptoms may be monitored with regular blood tests.

JAK inhibitors

• ruxolitinib, fedratinib, pacritinib and momelotinib reduce spleen size and symptoms such as night sweats, itching and fatigue. Momelotinib also helps anemia; pacritinib can be used with very low platelets.
• They do not cure the disease but improve quality of life and may extend survival.

Treating anemia

• red blood cell transfusions
• erythropoiesis-stimulating agents, danazol, luspatercept or momelotinib in selected patients

Other treatments

• hydroxyurea for high blood counts
• splenectomy or radiation to the spleen in selected cases
• clinical trials of new agents

Stem cell transplant

Allogeneic stem cell transplant is the only potentially curative treatment. It carries significant risks and is generally offered to fit patients with intermediate- or high-risk disease.

Complications

• worsening anemia and transfusion dependence
• painful spleen enlargement, splenic infarction
• portal hypertension
• blood clots or bleeding
• infections
• transformation to acute myeloid leukemia in about 10% to 20% over 10 years

Outlook

Survival varies widely, from 1 to 2 years in high-risk disease to well over 10 years in low-risk patients. Risk scores help estimate individual outlook. Treatment advances are improving symptom control and quality of life.

Frequently asked questions

What are the first symptoms of myelofibrosis?

Early symptoms often include tiredness from anemia, a feeling of fullness or pain under the left ribs from an enlarged spleen, night sweats, itching and unexplained weight loss. Some people have no symptoms and are diagnosed from abnormal blood tests.

Is myelofibrosis a type of cancer?

Yes. Myelofibrosis is a chronic blood cancer, classified as a myeloproliferative neoplasm. It usually progresses slowly but can transform into acute myeloid leukemia in some people.

What is the life expectancy with myelofibrosis?

It ranges widely, from a few years in high-risk disease to more than 10 to 15 years in low-risk disease. Doctors use risk scores based on age, blood counts, symptoms and genetic mutations to estimate an individual's outlook.

Can myelofibrosis be cured?

The only potential cure is an allogeneic stem cell transplant, which is suitable for some patients. Other treatments, such as JAK inhibitors, control symptoms and spleen size and improve quality of life but do not eliminate the disease.