Primary Myelofibrosis

What is Polycythaemia vera

Primary myelofibrosis (PMF) is a rare, chronic disorder in which the development of fibrosis in the bone marrow interferes with blood cell production, which can lead to anaemia, bleeding, and enlargement of the spleen and liver.

The outlook for patients diagnosed with PMF depends on multiple factors; some individuals remain symptom-free without intervention for many years, whereas others require aggressive treatment

Cause

PMF arises due to genetic mutations in bone marrow stem cells, but the cause of these changes is unknown.

Symptoms

The clinical signs and symptoms of PMF include:

• Cytopenia including severe anaemia
• Hepatosplenomegaly
• Fatigue
• Night sweats
• Fever
• Bone pain
• Pruritus

Complications include bleeding, thrombosis, and progression to acute leukaemia, the latter occurring in approximately 20% of patients.

Diagnosis

Clinical and laboratory parameters are assessed according to the 2016 World Health Organisation (WHO) diagnostic criteria, which distinguish a pre-fibrotic and an overtly fibrotic stage of the disease.
 

All of the following major criteria for must be met for diagnosis of PMF:

• Typical megakaryocyte changes accompanied by reticulin/collagen fibrosis (≥ grade 2 for overtly fibrotic PMF and ≤ grade 1 for pre-fibrotic PMF)
• Presence of JAK2, CALR or MPL mutations, or presence of other clonal markers, or absence of evidence for reactive bone marrow fibrosis
• WHO criteria for other myeloid neoplasms not met

Additionally, one of the following minor WHO criteria must be met:

• Unexplained anemia
• Leukocytosis ≥ 11 × 109 /L
• Palpable splenomegaly
• Increased serum lactate dehydrogenase
• A leukoerythroblastic blood smear (applies only for pre-fibrotic PMF)