Myelofibrosis is a rare and life-threatening blood cancer in which the bone marrow is replaced by scar tissue.1 It affects approximately 1 in every 100,000 people and has similar survival rates as other malignancies, such as breast cancer and colon cancer.2-6 In myelofibrosis, bone marrow does not function properly, causing other organs to take over the production of blood cells, including the spleen, which often becomes enlarged.7 Patients may also suffer debilitating symptoms, including fatigue/weakness, shortness of breath, fever, night sweats, itchy skin, bone/joint pain, abdominal pain and/or weight loss.1,8 Patients living with myelofibrosis may have a poor quality of life and shortened survival rate.6,8
Myelofibrosis is part of a group of related blood cancers known as myeloproliferative neoplasms (MPNs).1 Approximately 90% of patients with myelofibrosis have mutations that directly or indirectly activate the JAK/STAT signaling pathway, which may explain the development of the disease.9
The goal of treatment in myelofibrosis is to prolong survival, and if possible, a cure, as per European LeukemiaNet guidelines. However, for most patients, treatment does not offer a cure. If prolongation of survival or a cure is not possible, the treatment goal is to reduce symptoms and improve quality of life.10
It is important that patients receive the best available treatment early in the course of their disease to ensure that they achieve the most optimal outcome.11 If left untreated, patients with myelofibrosis can experience a significantly higher disease burden and may have a lower life expectancy than patients who receive treatment. The disease can also progress more rapidly, eventually becoming fatal.12,13 Common types of treatments include:
Bone marrow or stem cell transplant: The only potential curative treatment option presented to younger patients whose disease state is more advanced. Because this treatment option involves high levels of chemotherapy or radiation therapy, it is accompanied with harmful side effects and not recommended for older patients.14
Targeted-drug therapy: Use of a targeted-drug agent to address the underlying factors that play a role in the development of myelofibrosis, specifically the dysregulation of the JAK/STAT pathway, which is hyperactivated in more than 90% of patients with myelofibrosis.9,15 Side effects vary depending on the targeted-drug therapy, but some common adverse events include low blood cell counts and/or low grade non-hematologic adverse events.16
Cytoreductive therapy: This treatment helps to decrease high platelet and white blood cell counts and treat complications of an enlarged spleen and other myelofibrosis symptoms. Patients who take this treatment alone can experience worsening symptoms or become resistant to or intolerant of treatment.7
Splenectomy (removal of the spleen): Procedure carried out to reduce severe pain and the feeling of fullness experienced by patients with myelofibrosis who have an enlarged spleen. Risks associated with splenectomy include infection and potential long term cardiovascular complications.7
Radiotherapy: This procedure is useful for a small number of patients to reduce spleen size and help alleviate other myelofibrosis-related symptoms. Radiation of the spleen is an option if a splenectomy cannot be performed on a patient.14
Patients should discuss with their hematologist the available treatments that best address their individual circumstances.
Questions to ask your doctor
What is my prognosis and how will myelofibrosis impact my quality of life?
What are my treatment choices?
What are my treatment plan and the treatment goal?
What are the expected benefits of each kind of treatment?
What are the risks of each treatment?
What are the side effects of each treatment?
How will each treatment affect my daily life?
Is there a benefit to starting treatment immediately and prior to the development of debilitating symptoms?
How will we know if the treatment is working?
How can I assess my symptoms?
Are there new treatments or clinical trials I should consider?
Titmarsh G, Duncombe A, McMullin M, et al. How Common are Myeloproliferative Neoplasms? A Systematic Review and Meta-analysis. Am. J. of Hematol. 2014:1-7.
Gangat N, Caramazza D, Vaidya R, et al. DIPSS-plus: A refined Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count and transfusion status. J Clin Oncol. 2011; 29:392-397.
Cervantes F, Dupriez B, Pereira A, et al. New Prognostic Scoring System for Primary Myelofibrosis Based on a Study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009; 113(13):2895-2901.
Cervantes F. How I Treat Splenomegaly in Myelofibrosis. Blood Cancer J. Oct 2011; 1(10): e37.
Mesa RA, Schwagera S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): An Evidence-Based Brief Inventory to Measure Quality of Life and Symptomatic Response to Treatment in Myelofibrosis. Leuk Res. 2009; 33:1199-1203.
Tefferi A. Primary myelofibrosis: 2014 Update on Diagnosis, Risk-Stratification, and Management. American Journal of Hematology. 2014; 89(9):915-925.
Barbui T, Barosi G, Birgegard G, Cervantes F, et al. Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet. Journal of Clinical Oncology. 2011;1-10.
Mesa RA, Shields Alan, Hare Thomas, et al. Progressive Burden of Myelofibrosis in Untreated Patients: Assessment of Outcomes in Patients Randomized to Placebo in the COMFORT-I study. Leuk Res. 2013 May 17; 37: 911– 916.
Tefferi A, Lasho TL, Jimma T, et al. One Thousand Patients with Primary Myelofibrosis: The Mayo Clinic Experience. Mayo Clin Proc. 2012;87(1):25-33.
Verstovsek S. Janus-Activated Kinase Inhibitors: A New Era of Targeted Therapies Providing Significant Clinical Benefit for Philadelphia Chromosome-Negative Myeloproliferative Neoplasms. Journal of Clinical Oncology. Mar 2011; 29 (7):781-783.