Primary Myelofibrosis (PMF)

Question 1

what is myelofibrosis?

Answer 1

• a reactive, reversible increase in bone marrow collagen often with extramedullary hematopoiesis (e.g. in the spleen)
• may be primary or secondary

Question 2

what is the underlying cause of primary myelofibrosis?

Answer 2

• results from the neoplastic transformation of a pluripotent hematopoietic stem cell
• the progeny cells stimulate bone marrow fibroblasts to produce excessive collagen

Question 3

what is the aetiology of primary myelofibrosis?

Answer 3

• JAK2
• CALR
• MPL

Question 4

what are the key haematologic features and complications of primary myelofibrosis?

Answer 4

• causes leukoerythroblastosis due to extramedullary hematopoiesis, leading to the release of nucleated red blood cells and myelocytes
• serum LDH is often elevated
• bone marrow failure results in anaemia and thrombocytopenia
• a third of patients develop rapidly progressive, chemotherapy-incurable acute leukaemia

Question 5

what is malignant myelofibrosis?

Answer 5

a rare variant of myelofibrosis characterised by:
- pancytopenia
- myeloblastosis
- marrow fibrosis

generally due to acute megakaryoblastic leukaemia

Question 6

what are the symptoms of primary myelofibrosis?

Answer 6

• may be asymptomatic
• anaemia
• splenomegaly
• malaise
• fever
• weight loss
• splenic infarction

Question 7

what are the investigations for primary myelofibrosis?

Answer 7

• FBC
• blood film
• bone marrow biopsy
• JAK 2 V617F/CALR/MPL mutational analysis

Question 8

what is the management of primary myelofibrosis?

Answer 8

• JAK2 inhibitor (e.g. ruxolitinib)
• cytoreductive therapy (e.g. hydroxycarbamide, interferon-alpha)
• ? thalidomide + prednisolone
• ? allogeneic stem cell transplant