What Are the Treatment Options for Primary Myelofibrosis?

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Primary myelofibrosis (PMF) is one of several blood disorders classified as a myeloproliferative neoplasms. Neoplasm is defined as an abnormal growth of tissue caused by a mutation and can be classified as benign (non-malignant), pre-malignant, or malignant. Myeloproliferative neoplasms are generally benign initially, but over time may turn into malignant (cancerous) disease.  

The mutation in PMF results in fibrosis (scarring) of the bone marrow. This scarring in the bone marrow disrupts the normal development of blood cells. Anemia is the most common laboratory finding. Leukocytosis (elevation in white blood cells) and thrombocytosis (elevated platelet count) are common but as the disease progresses, thrombocytopenia (low platelet count) may occur. Splenomegaly (enlargement in the spleen) develops as the spleen becomes a secondary site of blood cell production.

Does Everyone Need Treatment?

While your typical first step might be to explore potential treatment options, remember that not not all people with PMF require treatment. Treatment for PMF is determined by risk of disease progression and overal survival.

A system called the Dynamic International Prognostic Scoring System (DIPSS) Plus score uses information about the person like age, white blood cell count, hemoglobin, circulating blast cells, presence of symptoms, genetics, platelet count, and transfusion need to calculate a score. Using this system people with PMF can be divided into four prognostic categories: low risk, intermediate-1 risk, intermediate-2 risk, and high risk. Median survival ranges from just over one year in patients with high risk disease to 15 years in patients with low risk disease. PMF in people under the age of 60 is associated with better prognosis and median survival of almost two years to 20 years.

Hematologists use the DIPPS Plus score along with the person's genetic mutation to determine a treatment plan. People with low-risk disease who do not have symptoms are not treated but monitored closely for symptoms and worsening anemia and/or thrombocytopenia. If a person develops symptoms (fever, weight loss, excessive sweating or massive enlargement of the spleen) or transfusion need, treatment should be initiated. Red blood cell transfusions are generally given when the hemoglobin is less than 8 g/dL. Because repeated red blood cell transfusions lead to iron overload, usually other treatments are attempted.  

Treatment of Symptoms

  • Splenomegaly: If the spleen is significantly enlarged and is causing issues (such as discomfort, multiple splenic infarcts, increasing transfusion need), the oral medication hydroxyurea may be used. With this treatment about 40 percent of people with PMF have a 50 percent reduction in spleen size lasting approximately one year. If the spleen does not respond to hydroxyurea therapy, splenectomy (surgical removal of the spleen) may be required. 
  • Anemia: Anemia in PMF may be treated with a variety of medications such as fluoxymesterone, prednisone, or danazol. Fluoxymesterone and danazol are known as androgens (a steroid hormone) which appear to stimulate bone marrow production. One of the major disadvantages of these medications is that they are related to male hormones and may cause development of body hair, deep voice, or increased muscle bulk. Thalidomide or lenalidomide (a form of chemotherapy) along with prednisone may also be used. 

High or Intermediate Risk

People with intermediate and high-risk disease may need alternative therapy. It's understandably difficult to hear that your disease is higher risk—knowledge of treatment options can help alleviate some of the worry and fear you may feel. 

  • Hematopoietic stem cell transplant (HSCT or bone marrow transplant): This is the only curative therapy for PMF but has significant risk. Transplantation should occur shortly after diagnosis prior to development of other complications to reduce complications. Historically, transplants have been limited to people under the age of 60 who have matched sibling donors (MSD). More recently transplants have been performed with matched unrelated or mismatched related donors.  
  • Ruxolitinib: People with PMF and severe symptoms who are not candidates for HSCT can use ruxolitinib. Ruxolitinib is a medication known as a tyrosine kinase inhibitor, specifically a JAK2 inhibitor. JAK2 is a common mutation in PMF but can also be found in other myleoproliferative neoplasms like polycythemia vera and essential thrombocythemia. Treatment with ruxolitinib can reduce spleen size, reduce symptoms (like fatigue, bone pain), and reduce anemia. Although this medication targets the JAK2 mutation, patients with other mutations may respond as well.  
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    Article Sources
    • Teferri A. Prognosis of Primary Myelofibrosis and Management of Primary Myelofibrosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2016.