Myelofibrosis (MF)
Characteristics
Myelofibrosis (MF) is a rare type of blood cancer that is characterized by the buildup of scar tissue (fibrosis) in the bone marrow. As a result of this increasing level of fibrosis, the bone marrow is no longer able to produce a sufficient amount of healthy blood cells, leading to a broad range of symptoms.
MF can develop on its own and in that case, it is called “primary MF.” However, other myeloproliferative neoplasms (MPN), such as polycythemia vera (PV) or essential thrombocythemia (ET) may also transform into MF. In these cases, the disease is known as “secondary MF”.
MF is a rare condition that can develop at any age. However, the majority of patients are diagnosed with MF above the age of 50. Also children can develop MF, but in that case most diagnoses are made before the age of 3. While in most MF patients the disease can be controlled with adequate therapy, some patients may develop serious complications, such as heart problems or severe infections. In about a fifth of patients, MF can develop into acute myeloid leukemia (AML).
The exact cause of primary MF is unclear. However, studies indicate that about 55% of patients have a mutation in the JAK2 gene which makes a protein that controls how many blood cells are produced in the bone marrow. In addition to this, about 35% and 8% of primary MF patients have a mutation in the CALR and MPL gene, respectively.
Symptoms
Because MF usually develops slowly and doesn’t cause symptoms at first, many patients find out that they have MF when they undergo a blood test for something else. However, as the disease progresses, symptoms will eventually develop.
Most of the symptoms in patients with MF are a result of reduced levels of the different blood cells in the blood stream. For example, a reduced level of red blood cells (anemia) can lead to weakness, fatigue, and shortness of breath. In contrast, a low level of blood platelets makes patients susceptible for bleeding (e.g., nosebleeds, bleeding gums, etc.) and bruising.
Another typical feature of MF consists of an enlarged spleen and liver, which may cause pain or discomfort in the tummy (abdomen) due to enlarged spleen and liver. Other symptoms that are associated with MF include bone pain, gout, a reduced appetite, unexplained weight loss, fever, night sweats and an itchy skin (especially after taking a bath or shower).
Finally, patients with MF have an increased risk for thrombosis. These blood clots can form everywhere in the body and can have serious consequences (e.g., heart attack, pulmonary embolism, stroke,…).
Diagnostic tests
Following a complete physical examination, the diagnostic process for MF usually starts with a complete blood count (CBC) to measure the level of the different blood cells. In the blood, a simultaneous increase in young white blood cells and young red blood cells is suggestive for MF (leuko-erythroblastic formula), but a bone marrow exam is necessary to make the diagnosis of MF. Genetic testing is performed on the bone marrow of patients who are eligible for allogeneic stem cell transplantation to check for unfavorable prognostic markers such as ASXL1.
Finally, patients with MF will usually have an ultrasound of the abdomen to check whether the spleen or liver are enlarged and undergo an MRI scan to evaluate the level of scarring in the bone marrow.
Treatments
When MF patients don’t experience symptoms of their disease, they usually don't need to start treatment immediately. Instead, they are monitored closely, with regular check-ups and blood tests.
For others, the treatment is largely supportive and is aimed at preventing complications due to low blood counts and an enlarged spleen (splenomegaly). First of all, blood transfusions are used to increase the number of red blood cells, which helps to control fatigue, breathlessness, and weakness. Also medication to stimulate the production of (red) blood cells are often used (e.g., erythropoietin stimulating agents). In addition, low-dose aspirin is given to reduce the thrombosis risk in MF patients. To lower the amount of uric acid in the blood as a result of increased red blood cell destruction, allopurinol can be prescribed.
For patients with an enlarged spleen or troublesome MF symptoms of MF, targeted therapy with a JAK2 inhibitor (e.g., ruxolitinib, fedratinib, momelotinib) can be initiated. For some patients, chemotherapy with hydroxycarbamide, or steroids can be considered.
In addition to this, immunomodulatory agents are often used in patients with MF. These agents can help to improve blood cell counts and may also relieve an enlarged spleen. These drugs are often given in combination with steroids.
An allogeneic stem cell transplantation is the only curative option, but it is only available for a minority of (young and fit) patients with a suitable donor.
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