Primary myelofibrosis
Update:
Recommendations for therapy have been expanded by the introduction of the JAK2 inhibitor Ruxolitinib.
Risk prognostication has been improved with the addition of thombocytopenia, transfusion need and unfavourable karyotype.
Myelofibrosis is a reactive process common to many malignant and benign disorders. Primary 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 primary 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 and splenomegaly is the most distressing complication, but the nonselective JAK2 inhibitor, Ruxolitinib, is effective in reducing spleen size and alleviating constitutional symptoms in a majority of patients and appears to improve survival in patients with advanced disease The few patients under 45 years of age, as well as those with advanced stage disease who have a matched, related donor should be considered for allogeneic bone marrow transplantation. Other therapies found to be effective include interferon, thalidomide and prednisone, low dose alkylating agents, hydroxycarbamide, splenectomy, and splenic irradiation. Oral folic acid is reasonable, and hyperuricaemia should be treated with allopurinol.
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