Myelofibrosis

Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It can present de novo as primary myelofibrosis (PMF), or as secondary (reactive) myelofibrosis if caused by another disorder, drug treatment, or toxic agent.

PMF (the focus of this topic) is a chronic progressive myeloproliferative neoplasm (MPN). Median survival is approximately 5 years, which is much shorter than that for other MPNs (polycythaemia vera, essential thrombocythaemia).

Bone marrow fibrosis, extramedullary haematopoiesis, leukoerythroblastosis, and splenomegaly are hallmarks of PMF.

Observation is appropriate for patients with asymptomatic, low-risk disease without hyperuricaemia or a remedial cause for anaemia.

Treatment with Janus kinase inhibitors (JAK) and haematopoietic stem cell transplant (along with supportive care) should be considered for patients with symptomatic and/or high-risk disease. Allogeneic haematopoietic stem cell transplant is the only treatment with curative potential.

Death is usually due to bone marrow failure (haemorrhage, anaemia, or infection), transformation to acute leukaemia, portal or pulmonary hypertension, heart failure, cachexia, or severe myeloid metaplasia with organ damage.

Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It is characterised by bone marrow fibrosis with increased reticulin deposits and in some cases increased collagen deposits. Depending on the underlying cause, patients may have abnormalities in blood production and associated extramedullary haematopoiesis.[1]Mesa RA, Verstovsek S, Cervantes F, et al. Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT). Leuk Res. 2007 Jun;31(6):737-40. http://www.ncbi.nlm.nih.gov/pubmed/17210175?tool=bestpractice.com

Myelofibrosis can present de novo as PMF, a chronic progressive MPN with its origin in a multipotent haematopoietic progenitor cell. The aetiology of PMF is unknown, but it is commonly associated with somatic driver mutations in the Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukaemia virus oncogene (MPL) genes. A specific clonal marker has not been identified.

Fibrosis in the bone marrow due to another disorder, drug treatment, or toxic agent is called secondary or reactive myelofibrosis.

This topic focuses on the diagnosis and management of primary myelofibrosis.