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Overview

Myelofibrosis (MF) is a rare disorder in which bone marrow scarring due to the production of excess fibrous tissue interferes with the normal production of blood cells. MF is characterized by a range of symptoms, including anemia, easy bleeding and bruising, fatigue, bone or joint pain, and splenomegaly.^1,2 The symptoms and progression of the disease vary from one individual to another.¹

Etiology of Myelofibrosis

MF can develop on its own (primary disease) or in association with another disorder (secondary disease).² The exact cause of MF is not fully understood, but in approximately 50% of patients with primary disease, a mutation of the JAK2 gene in blood stem cells is identified.¹ Mutations of the CALR gene are observed in approximately 20% of patients.¹ Other genetic defects underlying the development of MF include MPL and TET2 mutations.³

Metastasis of a primary tumor to the bone marrow may cause MF, and diseases such as polycythemia vera and essential thrombocythemia may lead to the development of secondary myelofibrosis.^1,2

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Prognosis of Myelofibrosis

The prognosis of patients with MF varies depending on the severity of the condition and individual patient factors. Because of the slow progression of MF, patients with the primary form of the disease may live longer than 10 years. Outcomes are often linked to bone marrow function.² In approximately 20% of cases, primary MF progresses to acute myelogenous leukemia, which is a blood cancer.¹ The prognosis of patients with secondary MF depends on the underlying disease.²

The International Prognostic Scoring System (IPSS) and the Dynamic IPSS (DIPSS) are useful for risk-stratifying patients at diagnosis and later in the course of their disease. The MIPSS70 (Mutation-Enhanced IPSS) is another useful score for the risk stratification of transplantation-age patients with primary MF.⁴

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Diagnosis of Myelofibrosis

MF is typically diagnosed with a physical examination, blood testing, and bone marrow biopsy. Bone marrow biopsy is essential for confirming the diagnosis and determining the severity of the condition.^1,2,5

During a physical examination, the clinician may examine the patient’s abdomen to detect an enlarged spleen. Imaging techniques, such as ultrasonography, are also used to determine the size of the spleen.^1,6

Blood testing with a complete blood cell (CBC) count and blood chemistry panel can be useful to diagnose MF by measuring blood cell levels and identifying markers of bone marrow fibrosis.⁵

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Treatment of Myelofibrosis

Treatment options for MF include medications that control symptoms and improve a patient’s quality of life. Treatments can also include blood transfusions, allogeneic hematopoietic stem cell transplant, and splenectomy.

Therapies

Several medications are used to treat MF, depending on the individual patient’s specific symptoms and needs.^1,2,5Bisphosphonates, such as Reclast® (zoledronic acid), can be used to relieve bone pain. JAK inhibitors, such as Jakafi® (ruxolitinib), can reduce the production of fibrous tissue in the bone marrow and relieve the symptoms of MF. Myelosuppressive agents, such as hydroxyurea and busulfan, can suppress the formation of blood cells in the bone marrow and relieve some of the symptoms associated with leukocytosis, thrombocytosis, and organomegaly.

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Blood Transfusions

Blood transfusions may be necessary to treat severe anemia. However, treatment with male hormones (androgens) and/or corticosteroids may increase the production of red blood cells and decrease the need for transfusions.¹

Splenectomy

Patients who have splenomegaly may be candidates for splenectomy surgery or splenic irradiation. However, both procedures are associated with risks that must be considered on a case-by-case basis.¹

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Allogeneic Stem Cell Transplant

In high-risk disease patients who meet the conditions, a hematopoietic stem cell transplant may be recommended to replace damaged bone marrow with healthy bone marrow from a donor. However, this procedure is associated with a high morbidity rate and early mortality.⁵

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References

1. Primary myelofibrosis. NORD (National Organization for Rare Disorders. Accessed December 18, 2022.

2. Liesveld J. Myelofibrosis. MSD Manual Consumer Version. Accessed December 19, 2022.

3. Primary myelofibrosis. Genetic and Rare Diseases Information Center (GARD). Accessed December 18, 2022.

4. Primary myelofibrosis. Orphanet. Accessed December 18, 2022.

5. Garmezy B, Schaefer JK, Mercer J, Talpaz M. A provider’s guide to primary myelofibrosis: pathophysiology, diagnosis, and management. Blood Rev. 2021;45:100691. doi:10.1016/j.blre.2020.100691

6. Myelofibrosis facts. Leukemia & Lymphoma Society (LLS). Accessed December 18, 2022.

Reviewed by Harshi Dhingra, MD, on 12/30/2022.

Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.

Myelofibrosis (MF)