Information
Editors
Myelofibrosis (Mf)
Essentials
- A chronic disease with no cure available.
- Occasionally, allogeneic stem cell transplantation can be used in young patients with the aim of achieving permanent cure.
- Anaemia is a common problem; other possible causes of anaemia should be excluded and treated as far as possible.
- Cytostatic chemotherapy may be used to suppress marked leukocytosis and thrombocytosis, as necessary.
- Ruxolitinib is used particularly to reduce the size of an enlarged spleen.
Definition
- MF is a chronic myeloproliferative disease that is caused by pathological proliferation of haematopoietic cells, especially megakaryocytes, and by the associated secondary fibrosis.
Epidemiology
- About 1 new case / 100 000 / year
- The peak incidence is at the ages of 40-70 years
- Equally common in men and in women
Aetiology
- The aetiology remains unknown.
- This is either a primary disease or develops from polycythaemia vera (PV) Polycythaemia Vera (PV) or essential thrombocythaemia (ET) Essential Thrombocythaemia (Et).
- The JAK2V617F gene mutation can be detected in about 50-60% of patients, the CALR (calreticulin) gene mutation in about 20% and the MPL gene mutation in a few percent. About 10% of patients are negative for all three mutations (triple-negative myelofibrosis).
Clinical picture
- Progression is usually slow at first, and there are few symptoms.
- Later on, general symptoms including abnormal, excessive sweating at night, slight fever, weight loss and impaired performance status (hypermetabolic symptoms)
- Growth of the spleen often leads to early satiety. Upper abdominal and flank pain is also common.
Laboratory and x-ray findings
- Blood picture
- Anaemia, most often normocytic
- Leukocytes often elevated. Leukoerythroblastic picture, i.e. a differential leukocyte count shows precursors of the neutrophil series (metamyelocytes/myelocytes) and nucleated precursors of erythrocytes (erythroblasts). A blood count shows precursors of leukocytes (metamyelocytes/myelocytes) that are normally not present.
- Varying platelet levels
- Dry tap on bone marrow aspiration Bone Marrow Examination and increased fibrosis (> 1) in trephine biopsy
- JAK2, CALR or MPL positive (some cases triple negative)
- LD often and urate sometimes elevated
- N.B.! Vitamin B12, folic acid and iron deficiency, for instance, should be excluded, as well as other malignancies, based on individual considerations.
- The initial workup includes upper abdominal ultrasonography to measure the sizes of the liver and the spleen.
Course of the disease
- This is a malignant disease with variable prognosis.
- Various scoring systems can be used to estimate the prognosis, such as IPSS, DIPSS, DIPSS plus, MIPSS70 or GIPSS. The scoring systems use parameters such as Hb, leukocytes, platelets, blast percentage from differential count and general symptoms.
- In the group with good prognosis, the remaining number of years may exceed 10-15 but in the group with poor prognosis it is 1-2 years, only.
- Increasing anaemia and increasing size of the spleen usually signify progression of the disease.
Complications
- Thromboembolic events, such as splenic infarction
- Bleeding problems (particularly at a late stage of the disease)
- Transformation to acute leukaemia (approx. 10-20%)
- Susceptibility to infections may increase, and a low Hb may predispose the patient to circulatory disturbances.
Treatment
- The treatment is symptomatic in a large share of patients.
- Treatment of anaemia with erythropoietin may be considered if the Hb level is about 100 g/l and EPO below 500 IU/l. Treatment with erythropoietin may enlarge the spleen.
- In about one patient in three, a response can be obtained by treating anaemia with anabolic hormones, of which danazol is the most commonly used.
- Ruxolitinib is increasingly often used to treat the enlarging spleen; it will also subdue the cytokine storm in the body, reducing any general symptoms.
- Radiotherapy of an enlarged spleen often effectively decreases the size of the spleen but often subsequently leads to severe cytopenias as extramedullary blood formation in the spleen ceases. For the same reason, splenectomy is not performed.
- Cytostatic chemotherapy (e.g. hydroxyurea) can be considered to lower leukocyte levels, for instance, but haemoglobin levels may also fall. Hydroxyurea can be used to try to prevent spleen enlargement or to reduce the size of the spleen. The results vary greatly.
- In patients less than 65 years of age, the possibility of allogeneic stem cell transplantation should be assessed.
- The overall treatment strategy should be planned by a haematologist or by a specialist in internal medicine with appropriate expertise.
References