What causes myelofibrosis? 

MF often starts when a mutation develops in a JAK2, CALR, or MPL gene. MF is generally notinherited. In rare cases, having a family history of MPNs may slightly increase risk, likely due to shared genetic factors that make these acquired mutations more likely to occur or expand.⁴ 

About half of people with MF have a JAK2  mutation. Many others have a CALR or MPL mutation. These activate pathways that make cells grow and divide too much, causing scarring in the bone marrow.¹˒⁴  Some people don't have any of these mutations. Their condition is managed the same way, based on symptoms and lab results. 

What are myelofibrosis symptoms? 

Early on, MF may notcause symptoms. When they appear, symptoms may include tiredness, weakness, shortness of breath, night sweats, fever, bone pain, and weight loss.¹

MF may affect your organs. When the bone marrow can't make enough blood cells, production may shift to the spleen or liver. The spleen canenlarge, causing pain or a full feeling under your ribs. You may also feel dizzy or lightheaded due to too few blood cells.¹ 

Less commonly, MF can also cause itching, easy bruising, or bleeding from low platelets (clotting blood cells). You may get infections more often when your white blood cell counts are low. Other symptoms can include trouble concentrating or feeling mentally tired. Everyone is different, and you may have different symptoms over time.¹ 

How is myelofibrosis diagnosed? 

Doctors often suspect MF after a routine blood test called a CBC. It looks at the number and type of blood cells. Results may show low red blood cell counts, unusual white blood cell counts, or platelet levels that are too high or too low.⁵ 

Doctors confirm MF with a bone marrow biopsy. This is essential to show scarring and abnormal cells. They will also order testing for JAK2, CALR, or MPLmutations and check the size of your spleen and liver.⁵ 

Myelofibrosis risks and outcomes 

Doctors use scoring systems to better understand how your MF may behave over time and what this may mean for you. They use information such as your age, symptoms, blood counts, bone marrow biopsy results, and genetic changes. Together, they help estimate both overall survival and the risk that MF could progress to a more aggressive blood cancer, such as acute leukemia. While some people develop acute leukemia, many do not. Your score helps your care team choose the most appropriate treatment and understand how closely to watch for changes or complications.⁶ 

Living with myelofibrosis and moving forward 

Living with MF means paying attention to your energy, general health, and risk of infection. It's important to pace yourself daily, eat a balanced diet to maintain strength and feel your best, and tell your care team if you think you are getting sick or have an infection. Emotional support is important. Joining a patient community or local support group can help reduce stress, encourage you, and remind you that you are not alone.¹ 

After your diagnosis, your care team will talk with you about the next steps. You may see different specialists depending on your specific needs. Expect regular blood tests, checkups, and changes to your plan as needed. Staying connected with your doctor and care team helps you and your family stay informed on the latest treatments and feel supported every step of the way.⁷ 

Organizations like MPN Research Foundation offer advocacy and research updates for people with MF. Getting involved means you can share experiences, find information, and keep up with scientific progress.¹ 

Managing and treating myelofibrosis (MF) 

When you have myelofibrosis, your bone marrow – the factory that makes blood cells – becomes scarred and can’t work properly. This affects how your body makes red blood cells, white blood cells, and platelets 

The main goals of treating myelofibrosis are to improve symptoms like fatigue and pain, reduce spleen size in people with enlarged spleens, improve blood cell counts, and help you feel better overall.¹  Most treatments help manage symptoms and improve how you feel every day. While a stem cell transplant can cure MF, it is not right for everyone who has MF. 

Stem cell transplant for myelofibrosis   

Stem cell transplants are usually considered for people with higher-risk MF who are healthy enough to undergo the procedure. Your doctor will take your overall health into account and may use risk-scoring tools to help determine whether a transplant is a recommended option for you. If not, other treatments are available to manage your symptoms and help you feel as well as possible. ¹˒² 

Risk assessment and scoring for myelofibrosis   

Doctors use scoring systems called IPSS, DIPSS, DIPSS-Plus, and MIPSS70+2.0 to learn how likely MF is to transform into leukemia.³  They count factors like age, symptoms, blood counts, and whether you have certain genetic changes. Your risk level – low, intermediate, or high – helps guide your treatment options. 

The active surveillance approach 

Low-risk people with no symptoms might just have checkups every 3 to 6 months. Doctors call this approach active surveillance.¹  During these visits, your doctor will check your blood counts, symptoms, and general health. If anything changes, you can start treatment as soon as necessary. 

JAK inhibitors – The main treatment for myelofibrosis 

Many people with MF have mutations such as JAK2, CALR, or MPL. Four approved medications can block their activity:  ruxolitinib, pacritinib, momelotinib, and fedratinib. These drugs are called JAK inhibitors. They calm the signals that cause inflammation and abnormal blood cell production. They can shrink an enlarged spleen and reduce symptoms like night sweats, itching, and fatigue.² 

Each JAK inhibitor works a little differently. Your doctor will choose the best one for you. 

• Ruxolitinib is often used first for people with intermediate and high-risk MF.¹˒⁵ 

• Pacritinib is designed for people with very low platelet counts. 

• Momelotinib may help if you also have anemia, a low red cell count. 

• Fedratinib is commonly used after ruxolitinib or to better control spleen symptoms.¹

Managing anemia in myelofibrosis 

More than half of people with myelofibrosis have anemia when they are first diagnosed.3 Treatment depends on the cause. After ruling out causes like low iron or vitamin B12, your doctor may prescribe medications to boost red blood cell production.¹ 

You may receive a blood transfusion or medication to treat anemia symptoms.4 Options may include erythropoiesis-stimulating agents, or ESAs, luspatercept, or adjusting your JAK inhibitor therapy.¹ 

Other helpful medications for myelofibrosis 

Hydroxyurea can help lower blood cell counts and reduce spleen size, though it is not specifically approved for myelofibrosis.⁵

Pegylated interferon may also help improve symptoms and manage blood counts.⁵ 

Managing an enlarged spleen 

An enlarged spleen can cause pain and an early feeling of fullness when you eat. JAK inhibitors usually help shrink the spleen.²  If medication does not help, low-dose radiation or surgery to remove the spleen may, although these are less common options. 

Supportive care for myelofibrosis   

Beyond medication, supportive care is important.⁶  This includes appropriate exercise to help manage fatigue, eating nutritious foods, not smoking, and treating anxiety or depression. You might need regular blood transfusions. You can work with your care team to adjust your treatment as needed. 

Clinical trials offer hope for myelofibrosis 

Clinical trials study new treatments for myelofibrosis. They may give you access to treatments before they are widely available. Some are testing new medications or combinations of treatments, including drugs used with ruxolitinib, to see if they can improve symptoms or reduce spleen size more effectively. Talk with your doctor about clinical trials you might qualify for. Organizations like MPN Research Foundation can also help you find trials. 

Living well with myelofibrosis  

Regular checkups, communicating with your doctor, and staying informed can help you live well with myelofibrosis. Many effective treatments are available to help you control MF symptoms and live as well as possible. Stay informed about your condition, work closely with your healthcare team, and remember that you’re not alone on this journey. 

Disclaimer: The information provided is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always consult your doctor about any questions you may have regarding a medical condition. 

“Understanding and Diagnosing Myelofibrosis (MF)” references

1. Vainchenker W, Constantinescu SN, Plo I. Recent advances in understanding myelofibrosis and essential thrombocythemia. F1000Res. 2016 Apr 19;5:F1000 Faculty Rev-700. 

2. Tefferi A, Lasho TL, Jimma T, Finke CM, Gangat N, Vaidya R, Begna KH, Al-Kali A, Ketterling RP, Hanson CA, Pardanani A. One thousand patients with primary myelofibrosis: the Mayo Clinic experience. Mayo Clin Proc. 2012 Jan;87(1):25-33. 

3. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR; Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25;365(9464):1054-1061. Erratum in: Lancet. 2005 Jul 9-15;366(9480):122. 

4. Koren-Michowitz M. Genetic predisposition to myeloproliferative neoplasms: another piece of the puzzle. Acta Haematol. 2018;139(4):238-239. 

5. Salama ME. Important pathologic considerations for establishing the diagnosis of myelofibrosis. Hematol Oncol Clin North Am. 2021 Apr;35(2):267-278. 

6. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010 Mar 4;115(9):1703-1708. 

7. Tefferi A. How I treat myelofibrosis. Blood. 2011 Mar 31;117(13):3494-3504 

“Managing anemia in myelofibrosis” references

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms, Version 3.2024. 
   https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477

2. Harrison CN, Schaap N, Vannucchi AM, et al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017 Jul;4(7):e317-e324. 

3. Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021 Jan;96(1):145-162. 

4. Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, et al. Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature. Br J Haematol. 2004 Nov;127(4):399-403. 

5. Kiladjian JJ, Mesa RA, Hoffman R. The renaissance of interferon therapy for the treatment of myeloid malignancies. Blood. 2011 May 5;117(18):4706-4715. 

6. Mesa R, Miller CB, Thyne M, , et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and prouctivity: the MPN Landmark survey. BMC Cancer. 2016 Feb 27;16:167.