Myelofibrosis (MF) is a rare, chronic, myeloproliferative neoplasm characterized by bone marrow fibrosis. Progressive fibrosis drives the clonal hematopoietic stem cells out of the bone marrow and into organs, such as the spleen and liver, to compensate for decreasing blood cell production with extramedullary hematopoiesis.1

Other Myeloproliferative Disorders

While most patients with MF present with primary MF, which arises spontaneously due to somatic genetic mutations, other patients develop secondary MF related to underlying disorders, which are most commonly other myeloproliferative disorders.2

The two other classic myeloproliferative disorders, polycythemia vera (PV) and essential thrombocythemia (ET), may progressively transform into secondary MF. Additionally, individuals diagnosed with primary MF may experience transformation to secondary acute myeloid leukemia (AML).3

A study conducted in South Korea reported that while transformation of PV and ET to secondary MF was rare, primary MF transformed into secondary AML with an incidence of 21.4% in the study population.3 

Several studies have reported that patients with myeloproliferative neoplasms demonstrate a 1.5- to 3-times higher risk of developing new cancers, such as lymphomas4 and solid tumors, especially in the brain, liver, lungs, prostate, thyroid, kidneys, and skin, than the general population.3,4

Read more about MF risk factors

Chronic Comorbid Conditions

Although MF can occur at any age, the condition predominantly affects individuals over the age of 50 years, with a median age at diagnosis of 65 years.1 Given the propensity for MF to occur in individuals over 50 years of age, other chronic comorbid conditions that frequently affect this age group are also present, impacting treatment decisions and overall patient prognosis.2,5

One study conducted in Spain that was published in 2022 reported the most common comorbidities among 668 patients with MF, which included hypertension (42.2%), diabetes (18.6%), dyslipidemia (16%), cardiovascular disease (15.7%), renal dysfunction (8.7%), pulmonary disease (8.2%), other neoplasms (8.2%), and hepatic disease (6.2%).2 

Another study published in 2014 reported that 64% of 349 patients with primary MF had at least 1 comorbidity. The most common comorbidities involved diseases of the cardiovascular system (63%). The researchers stressed the impact that comorbidities had on patient survival and risk stratification, particularly among those under 65 years of age.5

Read more about MF prognosis

As part of the disease process, patients with MF often present with disease-related comorbidities, such as progressive anemia causing chronic fatigue and weakness, splenomegaly and/or hepatomegaly due to extramedullary hematopoiesis, and constitutional symptoms such as night sweats, weight loss, pruritus, low-grade fever, and bone pain.2

Additional disease-related comorbidities include thrombocytopenia, which increases bleeding risk,6,7 and thrombocytosis, which primarily increases thrombosis risk.7 

Read more about MF signs and symptoms

Although patients with all 3 classic myeloproliferative neoplasms (primary MF, PV, and ET) have an increased risk of infection, patients with primary MF demonstrated the highest infection risk, according to a population-based cohort study in Sweden of 8363 patients with myeloproliferative neoplasms.8 

Read more about MF types

Bone marrow fibrosis leads to increased bone density in patients with MF. These changes in bone density had inverse relationships with ferritin levels and bone marrow cellularity but no negative correlations with erythropoietin or hemoglobin.9 Osteosclerosis in patients with primary MF promotes progression to bone marrow failure, leading to many disease-related complications.10

In murine models of PV, abnormal proliferation of bone marrow cells was correlated with bone loss and decreased osteoblastic activity.11 Correspondingly, patients with myeloproliferative disorders such as PV and ET (which may progress to secondary MF) demonstrate an increased risk of osteoporotic fractures.12 A longitudinal study in Sweden from 1995 to 2015 reported an increased incidence of hip and vertebral fractures among patients with myeloproliferative neoplasms.13

Read more about MF complications


  1. Primary myelofibrosis. National Organization for Rare Disorders (NORD). Accessed December 28, 2022.
  2. García-Fortes M, Hernández-Boluda JC, Álvarez-Larrán A, et al; Grupo Español de Enfermedades Mieloproliferativas Filadelfia Negativas Gemfin. Impact of individual comorbidities on survival of patients with myelofibrosis. Cancers (Basel). 2022;14(9):2331. doi:10.3390/cancers14092331
  3. Hong J, Lee JH, Byun JM, et al. Risk of disease transformation and second primary solid tumors in patients with myeloproliferative neoplasms. Blood Adv. 2019;3(22):3700-3708. doi:10.1182/bloodadvances.2019000655
  4. Brabrand M, Frederiksen H. Risks of solid and lymphoid malignancies in patients with myeloproliferative neoplasms: clinical implications. Cancers (Basel). 2020;12(10):3061. doi:10.3390/cancers12103061
  5. Newberry KJ, Naqvi K, Nguyen KT, et al. Comorbidities predict worse prognosis in patients with primary myelofibrosis. Cancer. 2014;120(19):2996-3002. doi:10.1002/cncr.28857
  6. Masarova L, Alhuraiji A, Bose P, et al. Significance of thrombocytopenia in patients with primary and postessential thrombocythemia/polycythemia vera myelofibrosis. Eur J Haematol. 2018;100(3):257-263. doi:10.1111/ejh.13005
  7. Kc D, Falchi L, Verstovsek S. The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review. Ann Hematol. 2017;96(10):1595-1604. doi:10.1007/s00277-017-3099-2
  8. Landtblom AR, Andersson TML, Dickman PW, et al. Risk of infections in patients with myeloproliferative neoplasms—a population-based cohort study of 8363 patients. Leukemia. 2021;35(2):476-484. doi:10.1038/s41375-020-0909-7
  9. Steer K, Stavnichuk M, Morris M, Komarova SV. Bone health in patients with hematopoietic disorders of bone marrow origin: systematic review and meta- analysis. J Bone Miner Res. 2017;32(4):731-742. doi:10.1002/jbmr.3026
  10. Karagianni A, Ravid K. Myeloproliferative disorders and their effects on bone homeostasis: the role of megakaryocytes. Blood. 2022;139(21):3127-3137. doi:10.1182/blood.2021011480
  11. Oikonomidou PR, Casu C, Yang Z, et al. Polycythemia is associated with bone loss and reduced osteoblast activity in mice. Osteoporos Int. 2016;27(4):1559-1568. doi:10.1007/s00198-015-3412-7
  12. Farmer S, Ocias LF, Vestergaard H, Broesby-Olsen S, Hermann AP, Frederiksen H. Bone morbidity in chronic myeloproliferative neoplasms. Expert Rev Hematol. 2015;8(4):447-456. doi:10.1586/17474086.2015.1053456
  13. Johansson P, Kristjansdottir HL, Johansson H, Jakir A, Mellström D, Lewerin C. Highly increased risk of fracture in patients with myeloproliferative neoplasm. Leuk Lymphoma. 2021;62(1):211-217. doi:10.1080/10428194.2020.1817437

Reviewed by Harshi Dhingra, MD, on 12/29/2022.