Idiopathic myelofibrosis

Myelofibrosis is a reactive process common to many malignant and benign disorders. Idiopathic myelofibrosis is a chronic myeloproliferative disorder of unknown aetiology that involves a multipotent haemopoietic progenitor cell and results in abnormalities in red cell, white cell, and platelet production in association with marrow fibrosis and extramedullary haemopoiesis.

Aetiology

This is unknown. Many chromosomal abnormalities have been found, and in about 50% of cases there is expression of the JAK2 V617F missense mutation typical of polycythaemia vera (see Chapter 22.3.8), but the mutation is not specific for idiopathic myelofibrosis.

Clinical features and prognosis

Many patients are asymptomatic at the time of diagnosis, but common presenting manifestations include fatigue, weight loss, night sweats, fever, dyspnoea, and abdominal discomfort due to splenomegaly (which may be massive). The major complications are the consequences of bone marrow failure and extramedullary haemopoiesis, which most commonly occurs in the spleen and liver, but can occur at any site and compromise organ or tissue function. About 20% of patients develop acute leukaemia as a terminal event.

Investigation and diagnosis

Anaemia is the most consistent abnormality, with the blood film showing evidence of a leucoerythroblastic reaction (presence of metamyelocytes, myelocytes, promyelocytes, myeloblasts, nucleated red cells, and tear drop-shaped red cells) due to extramedullary haemopoiesis. The presence of marrow fibrosis is essential for diagnosis and usually results in the inability to aspirate marrow from a properly placed needle (‘dry tap’).

Treatment

There is no specific treatment. Aside from supportive care, oral administration of folic acid and a trial of oral pyridoxine are reasonable, and hyperuricaemia should be treated with allopurinol. The few patients under 45 years of age who have a matched, related donor should be considered for allogeneic bone marrow transplantation, in the absence of which a variety of other treatments (e.g. thalidomide and prednisolone) have been tried, often more in hope than expectation of benefit. Splenomegaly is the most distressing complication: reduction in splenic size can be achieved with interferon, thalidomide, alkylating agents, hydroxycarbamide, splenectomy, or splenic irradiation. JAK2 inhibitors, currently in clinical trials, have proved effective in reducing splenomegaly and constitutional symptoms.