The terms myelosclerosis and myelofibrosis are interchangeable.
There is clonal proliferation of stem cells and extramedullary haemopoiesis in the liver and spleen. There is increased fibrosis in the bone marrow caused by hyperplasia of abnormal megakaryocytes which release fibroblast-stimulating factors such as platelet-derived growth factor. In about 25% of cases there is a preceding history of PV.
The disease presents insidiously with lethargy, weakness and weight loss. Patients often complain of a ‘fullness’ inthe upper abdomen due to splenomegaly. Severe pain related to respiration may indicate perisplenitis secondary to splenic infarction, and bone pain and attacks of gout can complicate the illness. Bruising and bleeding may occur due to thrombocytopenia or abnormal platelet function.
• Massive splenomegaly (for other causes)
ANAEMIA with leucoerythroblastic features is present. Poikilocytes and red cells with characteristic tear-drop forms are seen. The wee may be over 100 x 109/1itre, and the differential wee may be very similar to that seen in chronic myeloid leukaemia; later leucopenia may develop.
THE PLATELET COUNT may be very high but, in later stages, thrombocytopenia occurs.
BONE MARROW ASPIRATION is often unsuccessful and this gives a clue to the presence of the condition. A bone marrow trephine is necessary to show the markedly increased fibrosis. Increased numbers of megakaryocytes may be seen.
THE PHILADELPHIA CHROMOSOME is absent; this helps to distinguish myelofibrosis from most cases of chronic myeloid leukaemia.
THE LAP SCORE is normal or high.
A HIGH SERUM URATE is present.
Lo w SERUM F0 LATE levels may occur owing to the increased haemopoietic activity.
The major diagnostic difficulty is the differentiation of myelofibrosis from chronic myeloid leukaemia as in both conditions there may be marked splenomegaly and a raised wee with many granulocyte precursors seen in the peripheral blood. The main distinguishing features are the appearance of the bone marrow and the absence of the Philadelphia chromosome in myelofibrosis. Fibrosis of the marrow, often with a leucoerythroblastic anaemia, can occur secondarily to leukaemia or lymphoma, tuberculosis or malignant infiltration with metatatic carcinoma, or to irradiation.
This consists of general supportive measures such as blood transfusion, folic acid, analgesics and allopurinol. rugs such as busulphan, chlorambucil and hydroxyurea are used to reduce metabolic activity and high wee and platelet levels; hydroxyurea is the commonest drug used. Chemotherapy and radiotherapy are used to reduce splenic size. If the spleen becomes very large and painful, and transfusion requirements are high, it may be advisabIe to perform splenectomy. Splenectomy may also result in relief of severe thrombocytopenia.
Patients may survive for 10 years or more; median survavalis is 3 years. Death may occur from transformation to a cute myeloblastic leukaemia in 10-20%. The most common causes of death are cardiovascular disease, infection and gastrointestinal bleeding.