Brief overview
- What is Myelofibrosis? Myelofibrosis is a chronic and progressive disease in which the bone marrow converts to connective tissue and thus loses its ability to produce blood cells.
- Course of the disease and prognosis: The course of the disease varies from individual to individual. The disease is curable only in rare cases, but often progresses slowly.
- Treatment: Treatment is aimed at alleviating symptoms and improving quality of life. Watch & Wait (wait and see your doctor for regular check-ups), medication (targeted therapy with so-called JAK inhibitors), radiation or removal of the spleen, stem cell transplantation.
- Causes: Myelofibrosis is caused by gene changes in the hematopoietic cells of the bone marrow. How this occurs is largely unknown.
- Risk factors: There are no risk factors that favor the development of the disease, but some affected individuals have a hereditary predisposition to develop myelofibrosis.
- Symptoms: Fatigue, shortness of breath, palpitations, tendency to recurrent infections and blood clots, bleeding of the skin and mucous membranes, weight loss, pain in the upper abdomen, headache, fever, night sweats.
- Diagnostics: blood test (often incidental finding!), bone marrow biopsy, ultrasound and computer tomography of spleen and liver, molecular genetic testing
What is myelofibrosis?
Myelofibrosis is the name given by physicians to a chronic disease in which the bone marrow turns into connective tissue and loses its ability to produce blood cells. The term is derived from the Greek word myelós for bone marrow. Fibrosis describes the abnormal proliferation of connective tissue in organs.
Other names for myelofibrosis include “osteomyelofibrosis” (OMF), “chronic myeloproliferative disease” (CMPE), and “chronic idiopathic myelofibrosis” (CIMF). However, these terms are outdated and have not been used in medical circles for several years.
How does normal blood formation work?
The bone marrow is the body’s major hematopoietic organ. It consists of connective tissue and stem cells that, among other things, form blood cells. It is found mainly in long bones (e.g. humerus and femur), in the vertebral bodies and in the pelvic bones. Functional blood cells mature from the stem cells via several intermediate stages. These include red and white blood cells and platelets. Doctors refer to the process of blood cell formation as hematopoiesis.
What happens in myelofibrosis?
In order to still produce new blood cells, hematopoiesis is outsourced to other organs (spleen, liver). Doctors refer to this as extramedullary (taking place outside the bone marrow) hematopoiesis. In the beginning, it is still possible to meet the need for blood cells. In later stages of myelofibrosis, the liver and spleen are no longer able to produce sufficient cells – the formation of blood cells comes to a standstill.
Forms of myelofibrosis
Together with polycythaemia vera (PV) and essential thrombocythemia (ET), myelofibrosis belongs to the group of “chronic myeloproliferative neoplasms” (MPN). Their common feature is that in all diseases increased blood cells or connective tissue cells are produced in the bone marrow.
Myelofibrosis occurs in two forms:
Primary myelofibrosis (PMF): primary myelofibrosis develops randomly during life, without previous disease. It is the most common form of myelofibrosis.
Secondary myelofibrosis (SMF): Secondary myelofibrosis develops from pre-existing disease (PV or ET).
Frequency
Is myelofibrosis fatal/curable?
Course
The course of myelofibrosis varies greatly from patient to patient. It is not possible to predict in which patient the disease will take a more gradual course and in which patient it will progress more rapidly. A general statement regarding life expectancy is therefore not possible. While some patients live for many years without symptoms, the disease progresses rapidly in others and ultimately ends fatally after months to a few years. The most frequent causes of death are the transition to acute myeloid leukemia, cardiovascular diseases and infections.
Prognosis
The individual course of the disease is crucial for the prognosis of myelofibrosis. This includes factors such as the age of the patient, the symptoms that occur and the blood values (number of blood cells, hemoglobin value). Another factor in the prognosis is whether and how well the patient responds to treatment.
Despite modern drugs and various treatment options, myelofibrosis is currently curable with drugs only in rare cases and only with stem cell transplantation. In about 20 percent of all patients, myelofibrosis progresses to acute leukemia (blood cancer) despite therapy.
How is myelofibrosis treated?
Treatment in the early disease phase
Watch & Wait: Not every patient requires immediate drug therapy. In patients who have no symptoms, the physician usually waits and performs regular check-ups. The patient only receives treatment when the first symptoms appear. If the patient and physician decide on the “watch & wait” strategy, it is important to keep the agreed-upon control appointments (e.g., blood tests) and to watch for typical symptoms.
Drugs that suppress the formation of new blood cells: At the beginning of the disease, the bone marrow initially still produces many blood cells. In this phase, it may be necessary to use drugs that suppress the formation of new blood cells.
Treatment in the late phase of the disease
As the disease progresses, fewer and fewer blood cells are produced, resulting in anemia and the typical myelofibrosis symptoms.
Blood transfusion: Blood transfusions help to keep the number of red blood cells stable and to alleviate the symptoms of anemia (pallor, fatigue, breathing difficulties).
Interferons: Similar results as with JAK inhibitors (reduction of the spleen) are achieved with so-called interferons. They are mainly used in very early forms of myelofibrosis.
Cortisone: Cortisone preparations are used especially in patients who develop fever. They improve anemia in some cases, but are controversial because they simultaneously suppress the immune system.
Irradiation of the spleen: Irradiation results in a reduction in the size of the spleen, thereby relieving gastrointestinal symptoms. However, its size increases again over time, so treatment may need to be repeated.
Removal of the spleen (splenectomy): In the late stages of myelofibrosis, the spleen is usually greatly enlarged. It presses on the stomach and intestines, causing pain and digestive problems (diarrhea, constipation). Removal of the spleen is associated with an increased risk of vascular occlusion (thrombosis): Among other things, the spleen serves as a storage site for platelets. If it is removed, the number of platelets in the blood increases. This increases the tendency to blood clots.
To ensure that the transplanted bone marrow is not rejected, the patient receives what is known as “conditioning therapy” before the transplant. It switches off the body’s own immune cells, which greatly increases the patient’s susceptibility to infection. Until the transferred bone marrow starts functioning and produces sufficient blood cells, the patient is exposed to a greatly increased risk of infection.
Allogeneic stem cell therapy is therefore only suitable for a small group of patients. It is usually performed only in younger patients who suffer from severe myelofibrosis but are otherwise in good general health.
Nutrition in myelofibrosis
There is no specific recommended diet for myelofibrosis. However, most myelofibrosis patients develop gastrointestinal symptoms such as constipation and bloating due to liver and spleen enlargement. In these cases, it is advisable to consume sufficient fiber (cereals, fruits, vegetables), drink enough fluids and avoid flatulent foods such as cabbage vegetables, onions and garlic.
What are the symptoms of myelofibrosis?
often by chance in the course of screening examinations.
Only in the further course does the feeling of illness intensify. Typical symptoms that occur as myelofibrosis progresses are:
- Upper abdominal pain and premature feeling of fullness due to enlargement of the spleen and liver
- Indigestion such as diarrhea, constipation
- Heartburn
- Low appetite, weight loss
- Embolism and thrombosis
- Paleness
- Shortness of breath
- Night sweats
- Fever
- Tingling and circulatory disturbances in hands and feet
- Itching (especially in PV)
- Bone pain and joint pain (in later stages of the disease)
- Increased bleeding tendency (frequent bruising, nosebleeds)
Causes and risk factors
The exact causes of myelofibrosis are unknown. In about 65 percent of all myelofibrosis patients, physicians find a characteristic genetic change on chromosome 9 in the patients’ blood stem cells. This genetic change, known as the JAK2 mutation (Janus kinase2 mutation), is also detectable in some of the patients with polycythaemia vera (PV) and essential thrombocythemia (ET).
Risk factors
The greatest risk factor for developing primary myelofibrosis is age. The older the age, the greater the likelihood of a JAK2 mutation. Currently, there is no evidence that a particular lifestyle or external influences such as ionizing radiation or chemical agents increase the likelihood of disease.
Secondary myelofibrosis develops from other chronic myeloproliferative disorders. A diagnosis of polycythaemia vera or essential thrombocythemia increases the risk of developing myelofibrosis.
Is myelofibrosis hereditary?
In many cases, myelofibrosis is triggered by a gene mutation in the hematopoietic stem cells. The mutation usually develops spontaneously in the course of life and is not passed on. How it occurs has not yet been clarified.
In some families, however, chronic myeloproliferative diseases occur more frequently. Doctors assume that those affected have a hereditary predisposition to these diseases: They carry a genetic makeup that favors the occurrence of the mutation (JAK2 mutation). However, only one percent of people with such a predisposition actually develop myelofibrosis.
Examination and diagnosis
Physical examination: During the physical examination, the physician palpates the abdomen, among other things, to determine whether the spleen and/or liver are enlarged.
Blood examination: At the beginning of the disease, an increase in platelets and a moderate increase in white blood cells predominate. Later, the distribution of cells in the blood picture changes – there is a deficiency of red blood cells, white blood cells and platelets. The red blood cells are usually also changed in shape. They are no longer round, but have a “teardrop” shape.
Ultrasound examination: An ultrasound examination can detect enlargement of the spleen and liver.
Molecular genetic testing: About 65 percent of all myelofibrosis patients have a JAK2 mutation. It can be detected by a special blood test.
Bone marrow aspiration: Since JAK2 mutations also occur in other diseases such as PV and ET, the next step is a bone marrow aspiration. Myelofibrosis can be reliably diagnosed on the basis of the typical changes. For this purpose, the physician takes samples from the bone marrow of the pelvic bone under local anesthesia and examines them under the microscope for typical changes.
Prevention
Since the cause of myelofibrosis is not precisely known, there are no scientific recommendations to prevent the disease. If myelofibrosis or other chronic myeloproliferative diseases (ET, PV) occur in a familial cluster and over at least three generations, doctors recommend human genetic counseling. Particularly in the case of a desire to have children, a specialist in human genetics will then assess the risk of the disease occurring in the planned offspring.
