Myelofibrosis: Diagnosis and Treatment

Author: Marisa Healy, BSN, RN
Last Reviewed: September 09, 2022

Myelofibrosis (MF) is a rare type of cancer that affects the bone marrow. Bone marrow is a spongy area in the center of your bones. When there are cancer cells in the bone marrow, your body has a hard time making healthy blood cells. “Myelo” means your spinal cord, where your bone marrow is. “Fibrosis” means scarring. The bone marrow fills with scar tissue (fibrosis).

MF may also be called primary myelofibrosis, chronic idiopathic myelofibrosis, myelofibrosis with myeloid metaplasia, or agnogenic myeloid metaplasia.

If your provider thinks you may have myelofibrosis, they may order tests, such as a bone marrow biopsy to look at your blood cells and molecular testing to look for gene mutations (changes) in the JAK2, CALR, and MPL genes.

How is myelofibrosis staged?

Myelofibrosis is not staged like other cancers. You must meet certain criteria to be diagnosed with myelofibrosis. The World Health Organization (WHO) has made the following criteria for the diagnosis of MF. You must meet all 3 major criteria as well as 1 minor criterion for a diagnosis. The criteria for MF can be complex and hard to understand. Your provider will go over any of the criteria listed below that you may have:

Major Criteria

  • A quick increase and an abnormality of megakaryocytes with either reticulin and/or collagen fibrosis grades 2 or 3 on a scale of 0-3.
  • Not meeting WHO criteria for ET, PV, BCR-ABL1 positive chronic myelogenous leukemia, myelodysplastic syndromes, or other myeloid neoplasms.
  • Having a JAK2, CALR, or MPL mutation. If you don’t have one of these mutations, you have another clonal marker or you don’t have reactive myelofibrosis.

Minor Criteria

  • Anemia (low red blood cell count) not caused by another health issue.
  • Leukocytosis (higher than normal white blood cell count ≥ 11 x 109/L).
  • Splenomegaly (enlarged spleen) that can be felt by your provider.
  • Higher than normal LDH (lactate dehydrogenase) level in the blood. A higher level of this enzyme can be caused by injuries and some diseases.
  • Leukoerythroblastosis (nucleated red blood cells and immature white blood cells).

How is myelofibrosis treated?

Treatment for MF depends on your symptoms, your age, and your overall health. Treatment may include:

Supportive Care

Supportive care is treatment that tries to lessen your symptoms. The goals of supportive care are to:

  • Help with symptoms of low blood counts.
  • Improve your quality of life.
  • Lower your risk of acute leukemia.

Supportive care treatments may be:

  • Androgen therapy (oxymetholone, danazol), a man made version of male hormones, can be used to improve anemia.
  • Erythropoietin is a medication that helps the body to make red blood cells and can improve anemia in some patients.
  • Hydroxyureais a medication that is thought to change the synthesis of DNA and is used in the treatment of other blood disorders. It has been shown to decrease the size of the spleen and help control high platelet and WBC counts.
  • Cladribine is a medication that may be able to prevent cells from reproducing by stopping DNA synthesis.
  • Bisphosphonates (Aredia, Zometa) are a type of medication that can relieve bone pain and help prevent bone loss.
  • Splenectomy is the removal of the spleen. An enlarged spleen can cause discomfort. Removal can relieve symptoms. Patients with MF and an enlarged spleen, low platelets, and needing frequent transfusions despite drug therapies may get some symptom relief from the removal of their spleen.

Targeted Therapies

Targeted therapy is medications that target the specific genes in MF. Ruxolitinib is currently the only medication with FDA approval for the treatment of MF. Ruxolitinib is a kinase inhibitor. A kinase inhibitor blocks an enzyme (protein) called a kinase. It helps treat MF by blocking cancer cells from multiplying. Other medications in this class are being studied in clinical trials.

Lenalidomide and thalidomideare immunomodulators and are also used in the treatment of myelofibrosis.

Interferon is an immune therapy that works by lowering the amount of unhealthy blood cells and reduces the cytokines that cause scarring (fibrosis) in the marrow. It appears to work best in those with early myelofibrosis secondary to PV or ET. Interferon has side effects that can be hard to manage.

Stem Cell Transplant

The only treatment that can cure myelofibrosis is an allogeneic stem cell transplant (where the bone marrow comes from a donor). Stem cell transplants can lead to serious side effects. For this reason, they are often only done if you are in good health, if you are younger than 60, and if you have a "matched" donor. Stem cell transplants are only done in young patients with high-risk disease.

Clinical Trials

You may be offered a clinical trial as part of your treatment plan. To find out more about current clinical trials, visit the OncoLink Clinical Trials Matching Service.

Making Treatment Decisions

Your care team will make sure you are included in choosing your treatment plan. This can be overwhelming as you may be given a few options to choose from. It feels like an emergency, but you can take a few weeks to meet with different providers and think about your options and what is best for you. This is a personal decision. Friends and family can help you talk through the options and the pros and cons of each, but they cannot make the decision for you. You need to be comfortable with your decision – this will help you move on to the next steps. If you ever have any questions or concerns, be sure to call your team.

References

Cordoba, R., Garcia-Gutierrez, V., & Alonso-Dominguez, J. M. (2020). Chronic Myelogenous Leukemia and Myeloproliferative Disorders in Older Adults. Geriatric Oncology, 535-547.

Harrison, C., Kiladjian, J. J., Al-Ali, H. K., Gisslinger, H., Waltzman, R., Stalbovskaya, V., ... & Cervantes, F. (2012). JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. New England Journal of Medicine, 366(9), 787-798.

Deisseroth, A., Kaminskas, E., Grillo, J., Chen, W., Saber, H., Lu, H. L., ... & Bullock, J. (2012). US Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clinical Cancer Research, 18(12), 3212-3217.

Kröger, N., Giorgino, T., Scott, B. L., Ditschkowski, M., Alchalby, H., Cervantes, F., ... & Maffioli, M. (2015). Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood, 125(21), 3347-3350.

Mesa, R. A., Gotlib, J., Gupta, V., Catalano, J. V., Deininger, M. W., Shields, A. L., ... & Harvey, J. H. (2013). Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology, 31(10), 1285-1292.

Tefferi, A. (2013). Primary myelofibrosis: 2013 update on diagnosis, risk‐stratification, and management. American Journal of Hematology, 88(2), 141-150.

Tefferi, A., Guglielmelli, P., Larson, D. R., Finke, C., Wassie, E. A., Pieri, L., ... & Ketterling, R. P. (2014). Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood,124(16), 2507-2513.

Tefferi, A., Lasho, T. L., Finke, C. M., Knudson, R. A., Ketterling, R., Hanson, C. H., ... & Pardanani, A. (2014). CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic, and molecular comparisons. Leukemia, 28(7), 1472-1477.

World Health Organization (2016). Diagnostic criteria for primary myelofibrosis, polycythemia vera, and essential thrombocytopenia. Retrieved from https://www.mpnconnect.com/pdf/who-diagnostic-criteria-mf-pv-et.pdf

Xu, P., Shen, P., Yu, B., Xu, X., Ge, R., Cheng, X., ... & Wang, J. (2020). Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myeloproliferative disorders. European Journal of Medicinal Chemistry, 112155.

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