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Myelofibrosis: description, course, treatment

by Josephine Andrews
Published: Last Updated on 139 views

Myelofibrosis is a chronic bone marrow disease from the group of “myeloproliferative neoplasms”. Over time, the bone marrow of those affected loses the ability to produce blood cells. Read here how the disease progresses, what signs point to myelofibrosis and how it is treated!

ICD codes for this disease:

ICD codes are internationally valid codes for medical diagnoses. They can be found, for example, in doctor’s letters or on certificates of incapacity for work.

D47

quick overview

  • What is myelofibrosis? Myelofibrosis is a chronic and progressive disease in which the bone marrow becomes connective tissue, thereby losing its ability to make blood cells.
  • Course of the disease and prognosis: The course of the disease varies from person to person. The disease can only be cured in rare cases, but often progresses slowly.
  • Treatment: Treatment aims to relieve symptoms and improve quality of life. Watch & Wait (Wait and see the doctor regularly), medication (targeted therapy with so-called JAK2 inhibitors), radiation or removal of the spleen , stem cell transplantation
  • Causes: Myelofibrosis is caused by genetic changes in the blood-forming cells of the bone marrow. How this happens is largely unknown.
  • Risk factors: There are no risk factors that favor the development of the disease, but some people have a hereditary tendency 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, epigastric pain, headache , fever, night sweats
  • Diagnostics: Blood tests (often incidental findings!), bone marrow biopsy, ultrasound and computed tomography of the spleen and liver, molecular genetic testing
  • Prevention: No preventive measures possible

What is myelofibrosis?

Doctors call myelofibrosis a chronic disease in which the bone marrow turns into connective tissue and loses its ability to form blood cells. The term derives from the Greek word myelós for bone marrow. Fibrosis describes the pathological proliferation of connective tissue in organs.

Other names for myelofibrosis are “osteomyelofibrosis” (OMF), “chronic myeloproliferative disorder” (CMPE) and “chronic idiopathic myelofibrosis” (CIMF). However, these terms are obsolete and have not been used in medical communities for several years.

How does normal blood formation work?

The bone marrow is the main blood-forming organ in the body. It consists of connective tissue and stem cells, which form blood cells, among other things. It is mainly found in tubular bones (eg upper arm and thigh bones), in the vertebral bodies and in the pelvic bones. Functional blood cells mature from the stem cells in several intermediate stages. These include red blood cells, white blood cells, and platelets. Doctors refer to the process of blood cell formation as hematopoiesis.

What happens in myelofibrosis?

In myelofibrosis, a malfunction in the stem cells initially leads to an increased production of bone marrow and blood cells. In the long term, the bone marrow is gradually replaced by connective tissue. It eventually loses its ability to make blood cells.

However, in order to be able to produce new blood cells, blood formation is outsourced to other organs (spleen, liver). Doctors speak of extramedullary (taking place outside of the bone marrow) blood formation. At the beginning it is still possible to cover the need for blood cells. In later stages of myelofibrosis, the liver and spleen are no longer able to produce enough cells – the formation of blood cells comes to a standstill.

forms of myelofibrosis

Together with polycythemia 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 over the course of life, without any previous illness. It is the most common form of myelofibrosis.

Secondary myelofibrosis (SMF): Secondary myelofibrosis develops from a pre-existing condition (PV or ET).

frequencies

Myelofibrosis is one of the rare diseases: 0.5 to 1.5 per 100,000 people develop it every year. The disease mainly occurs in old age: on average, patients are 65 years old when they are diagnosed, and at 65 percent men are affected somewhat more often than women. Young adults fall ill comparatively rarely, PMF is practically non-existent in children.

Is myelofibrosis fatal/curable?

Course

Myelofibrosis progresses very differently from patient to patient. It cannot be predicted in which patient the disease will be more insidious and in which patient it will progress more rapidly. A general statement regarding life expectancy is therefore not possible. While some of the patients live many years without symptoms, in others the disease progresses rapidly and ultimately ends fatally after months to a few years. The most common causes of death are the transition to acute myeloid leukemia, cardiovascular disease and infections.

forecast

The individual course of the disease is decisive for the prognosis of myelofibrosis. These include 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 prognosis is whether and how well the patient responds to treatment.

Despite modern medication and various treatment options, myelofibrosis can currently only be cured with medication in rare cases and only with a stem cell transplant . In about 20 percent of all those affected, myelofibrosis progresses to acute leukemia (blood cancer) despite therapy.

How is myelofibrosis treated?

Treatment of myelofibrosis is usually aimed at relieving symptoms of the disease and maintaining quality of life. Despite modern therapies, complete healing with medication is not possible in most cases. The only way to cure the disease is stem cell transplantation. However, this is associated with risks and is not suitable for every myelofibrosis patient.

Treatment in the early phase of the disease

Watch & Wait: Not every patient requires immediate drug therapy. For patients who do not have any symptoms, the doctor usually waits and carries out regular check-ups. The patient only receives treatment when the first symptoms appear. If patient and doctor opt for the “watch & wait” strategy, it is important to keep to the agreed check-up appointments (eg blood tests) and to pay attention to typical symptoms.

Drugs that suppress the formation of new blood cells: At the beginning of the disease, the bone marrow initially 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 keep red blood cell counts stable and relieve symptoms of anemia (pallor, tiredness, difficulty breathing).

Janus kinase inhibitors (JAK inhibitors): For the treatment of myelofibrosis, so-called Janus kinase inhibitors have been on the market for several years. The active substance ruxolitinib (inhibits JAK 1 and 2), for example, is usually well tolerated and in many cases improves the symptoms. Symptoms such as fever, night sweats, bone pain and weight loss are significantly reduced. They also lead to a reduction in the size of the spleen and liver. The duration of therapy is not limited in time. Alternatively, or if ruxolinitib is not working satisfactorily, the active ingredient fedratinib is used.

Interferons: Similar results as with JAK inhibitors (reduction of the size of the spleen) are achieved with so-called interferons. They are mainly used in very early forms of myelofibrosis.

Cortisone: Cortisone preparations are used in particular in patients who develop fever. They improve anemia in some cases, but are controversial because they also suppress the immune system.

Irradiation of the spleen: The irradiation reduces the size of the spleen and thus alleviates gastrointestinal complaints. However, their size will increase over time, so treatment may need to be repeated.

Removal of the spleen (splenectomy): In the late phase of myelofibrosis, the spleen is usually greatly enlarged. It presses on the stomach and intestines , causing pain and indigestion (diarrhea, constipation ). The removal of the spleen is associated with an increased risk of vascular occlusion (thrombosis): the spleen is used, among other things, as a storage location for blood platelets. If it is removed, the number of platelets in the blood increases. This increases the tendency for blood clots.

Stem cell transplantation: The only way to cure myelofibrosis is currently the so-called allogeneic stem cell transplantation. Healthy stem cells from the bone marrow or blood of a donor are transferred to the patient. “Allogeneic” means that the stem cells do not come from the patient themselves, but from a healthy donor. The aim of the treatment is for the transferred blood stem cells to form functional blood cells again on their own.

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 defense cells, which greatly increases the patient’s susceptibility to infection. Until the transferred bone marrow starts to function and produces enough blood cells, the patient is exposed to a greatly increased risk of infection.

Allogeneic stem cell therapy is therefore only an option for a small group of patients. It is usually only performed on younger patients who have severe myelofibrosis but are otherwise in good general health.

Diet in myelofibrosis

There is no specific recommended diet for myelofibrosis. However, most myelofibrosis patients develop gastrointestinal symptoms such as constipation and bloating because of the enlarged liver and spleen. In these cases, it is advisable to eat enough fiber (cereals, fruit, vegetables), drink enough and avoid flatulent foods such as cabbage, onions and garlic .

What are the symptoms of myelofibrosis?

The symptoms of myelofibrosis depend on the stage of the disease. Especially at the beginning of the disease, the symptoms are still very unspecific. Symptoms such as tiredness, exhaustion and increased susceptibility to infections also occur in the context of many other diseases and do not initially lead to the suspicion of the rare bone marrow disease. For this reason, the diagnosis is usually made late, when there are changes in the blood count –

often accidentally during preventive medical check-ups.

Only as the disease progresses does the feeling of illness intensify. Typical symptoms that occur as myelofibrosis progresses are:

  • Upper abdominal pain and premature fullness due to enlargement of the spleen and liver
  • Digestive disorders such as diarrhea, constipation
  • heartburn
  • Little appetite, weight loss
  • embolism and thrombosis
  • paleness
  • shortness of breath
  • night sweats
  • fever
  • Tingling and circulatory problems in hands and feet
  • itching (especially in PV)
  • Bone pain and joint pain (in later stages of the disease)
  • Increased tendency to bleed (frequent bruising, nosebleeds)

Causes and risk factors

The exact causes of myelofibrosis are unknown. In about 65 percent of all myelofibrosis patients, doctors find a characteristic gene change on chromosome 9 in the blood stem cells of the patients of essential thrombocythemia (ET).

The JAK2 mutation initially causes white blood cells and platelets to multiply uncontrollably. At the same time, the massive formation of blood cells stimulates the formation of so-called “growth factors”. These in turn stimulate bone marrow cells to produce connective tissue cells. The bone marrow is increasingly displaced by connective tissue, which is why fewer and fewer functional blood cells are formed. The body tries to compensate for the deficiency and shifts blood formation to other organs. The blood cells are now mainly produced in the spleen and to a lesser extent in the liver. The result: Both organs enlargement. It is not known how the triggering gene change occurs.

risk factors

Age is the greatest risk factor for the development of primary myelofibrosis. The older the age, the greater the likelihood of a JAK2 mutation. There is currently no evidence that a certain lifestyle or external influences such as ionizing radiation or chemical substances increase the likelihood of the disease.

Secondary myelofibrosis develops from other chronic myeloproliferative diseases. The diagnosis of polycythemia vera or essential thrombocythemia increases the risk of developing myelofibrosis.

Is myelofibrosis hereditary?

In many cases, myelofibrosis is triggered by a genetic mutation in the stem cells involved in blood formation. The mutation usually develops spontaneously over the course of life and is not passed on. How this comes about has not yet been clarified.

However, chronic myeloproliferative disorders are more common in some families. Physicians assume that those affected have a hereditary tendency to these diseases: They carry genetic material that favors the occurrence of the mutation (JAK2 mutation). However, only 1% of people with such a tendency actually develop myelofibrosis.

examination and diagnosis

Around a quarter of patients have no symptoms at the time they are diagnosed with “myelofibrosis”. Since the symptoms are very non-specific, especially at the beginning of the disease (fatigue, tiredness, increased susceptibility to infections), most myelofibrosis patients see a doctor late. Most of the time, the altered blood values ​​​​are noticed during other examinations (eg check-ups) by the general practitioner. If chronic myeloproliferative disease is suspected, the general practitioner usually refers the patient to a hematologist (a doctor who specializes in blood disorders).

Physical exam: During the physical exam, the doctor feels, among other things, the abdomen to determine whether the spleen and/or liver is enlarged.

Blood test: At the beginning of the disease, an increase in platelets and a moderate increase in white blood cells predominate. Later, the distribution of the cells in the blood changes – there is a lack of red and white blood cells and platelets. The red blood cells are also usually changed in shape. They are no longer round, but have a “teardrop” shape.

Ultrasound scan: An ultrasound scan can detect enlargement of the spleen and liver.

Molecular Genetic Analysis: About 65 percent of all myelofibrosis patients have a JAK2 mutation. It can be detected by a special blood test.

Bone marrow biopsy: Since JAK2 mutations are also found in other diseases such as PV and ET, the next step is a bone marrow biopsy. Myelofibrosis can be reliably diagnosed on the basis of the typical changes. For this purpose, the doctor takes samples from the bone marrow of the pelvic bone under local anesthesia and examines them under the microscope for typical changes.

As a rule, two different samples are taken from the bone: on the one hand, liquid bone marrow is sucked out with a thin needle, on the other hand, the doctor carries out a punch biopsy. To do this, he removes a small bone cylinder from the pelvic bone. In the final stages of the disease, there is no liquid bone marrow left. Doctors then speak of a “dry marrow”.

Prevent

Since the exact cause of myelofibrosis is not known, there are no scientific recommendations to prevent the disease. If myelofibrosis or other chronic myeloproliferative diseases (ET, PV) accumulate in families and occur over at least three generations, doctors recommend genetic counseling. A specialist in human genetics then estimates the risk of the disease occurring in the planned offspring, especially if you wish to have children.

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