Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders.
Primary myelofibrosis (PMF) is a chronic progressive myeloproliferative disorder with a median survival (around 5.5 years) much shorter than that of other myeloproliferative disorders. However, PMF survival is heterogeneous, ranging from <1 year to >30 years.
Leukoerythroblastosis and splenomegaly are the clinical hallmarks of PMF.
Death is usually due to bone marrow failure (haemorrhage, anaemia, or infection), transformation to acute leukaemia, portal or pulmonary hypertension, heart failure, cachexia, or myeloid metaplasia with organ failure.
Asymptomatic, low-risk patients without hyperuricaemia or a remedial cause for anaemia require no therapy.
Haematopoietic stem cell transplant is the only treatment option with a potential for cure.
Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It is characterised by abnormal production of red blood cells, white blood cells, and platelets, in association with marrow fibrosis (scarring) and extramedullary haematopoiesis. It can present de novo as primary myelofibrosis (PMF), a chronic progressive myeloproliferative disorder with its origin in a multipotent haematopoietic progenitor cell. The aetiology of PMF is unknown, and a specific clonal marker has not been identified. Leukoerythroblastosis and splenomegaly are the clinical hallmarks of PMF. When fibrosis in the bone marrow is due to a known diagnosis such as leukaemia, hypoparathyroidism, or drugs, it is called secondary or reactive myelofibrosis.
History and exam
Key diagnostic factors
- presence of risk factors
- constitutional symptoms (weight loss, night sweats, low-grade fever, cachexia, fatigue, and pruritus)
- splenomegaly ± hepatomegaly
- features of extramedullary haematopoiesis
Other diagnostic factors
- features of portal hypertension
- symptoms of pulmonary hypertension
- joint and bone pain
- hearing loss
- radiation exposure
- industrial solvents exposure
- age >65 years
1st investigations to order
- FBC with differential
- peripheral blood smear
- bone marrow aspiration
- bone marrow biopsy
Investigations to consider
- genetic mutation analysis (JAK2 V617F, calreticulin [CALR], MPL)
- breakpoint cluster region-abelson polymerase chain reaction (BCR-ABL PCR)
- chromosomal assessment in bone marrow examination
- CD34+ cell count
- antinuclear antibodies
- rheumatoid factor titre
- complement levels
- Coombs' test
- ultrasound of suspected site
- technetium 99 scan
- CT of suspected site
- MRI of suspected site
- serum uric acid
symptomatic: aged <50 years and suitable for stem cell transplant
symptomatic: aged ≥50 years and suitable for stem cell transplant
symptomatic: not suitable for stem cell transplant
- Polycythaemia vera
- Essential thrombocythaemia
- Chronic myelogenous leukaemia
- Use of JAK inhibitors in the management of myelofibrosis: a revision of the British Committee for Standards in Haematology guidelines for investigation and management of myelofibrosis 2012
- Guideline for the diagnosis and management of myelofibrosis
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