Causes
Myelofibrosis is thought to result from abnormal bone marrow stem cells. The abnormal cells produce growth factors which stimulate scar tissue in the bone marrow. In some patients myelofibrosis follows on from polycythaemia vera or essential thrombocythaemia. There are Leukaemia Research Fund leaflets available on these two conditions. However in other patients there is no evidence of prior polycythaemia vera or essential thrombocythaemia, and in these patients the term primary myelofibrosis is used. The cause of primary myelofibrosis is unknown.

Signs and Symptoms
Some patients have no symptoms and myelofibrosis may be discovered as a chance finding after a routine blood test. More usually patients feel tired or breathless because of anaemia, or notice some abdominal discomfort resulting from the presence of a large spleen.

Diagnosis
Myelofibrosis is usually suspected following the results of a simple blood test which measures the number of the various blood cells. Abnormally shaped red cells are characteristic. Confirmation of the diagnosis requires a number of subsequent investigations, and analysis of a bone marrow sample to detect the scar tissue. This involves obtaining a small amount of marrow from inside the bone with a needle, and a sample from the bone itself showing the structure of the bone marrow cavity. The first is known as a bone marrow aspirate, the second as a bone marrow trephine. The trephine will show the fibrosis which is characteristic of the disease. The samples are usually obtained from the back of the hip bone, although the sternum (breast bone) may be used instead for bone marrow aspirates (but not for trephines). The procedure causes some discomfort but does not take very long. The procedure is usually carried out with sedation as well as local anaesthetic.

Treatment
The appropriate choice of treatment for an individual patient with myelofibrosis will depend on the details of each case. Patients who do not have severe anaemia and have no symptoms are usually seen regularly in the out-patient clinic but may not need treatment.

Patients who have severe anaemia will require regular blood transfusions, usually every one to three months. These can usually be carried out during the day without the patient having to stay in hospital overnight. In some patients an enlarged spleen may cause problems by becoming painful or by consuming normal blood cells and thus making the anaemia worse. In such cases the large spleen may respond to drugs (e.g. hydroxyurea). Alternatively an operation to remove the spleen (splenectomy) can be helpful. There is a factsheet on Splenectomy and Infection available from the Leukaemia Research Fund. The course of myelofibrosis is very variable. Some patients have a mild disease which does not progress rapidly. In such cases the condition is relatively benign and need not interfere significantly with the patient’s activity and working life. In other cases the disease progresses more quickly and patients become dependent on blood transfusions. Finally a small proportion of patients with myelofibrosis may develop acute myeloid leukaemia. There is a Leukaemia Research Fund booklet available on Acute Myeloid Leukaemia.

The usual management of myelofibrosis is to endeavour to keep the patient comfortable and well without upsetting them with the side-effects of the treatment. In such a chronic condition with such a variable outcome, predictions of how an individual case will develop and what line of treatment should be followed must be determined individually between the patient and their doctor(s). Occasionally the disease changes into acute myeloid leukaemia which then tends to have a poor outlook.

Source: Leukemia Research Fund.