Osteomyelofibrosis is a very rare, chronic, and incurable disease of the bone marrow. It is associated with progressive restriction of blood cell formation, leading to various complications such as anemia, bleeding, and increased risk of infection.
What is osteomyelofibrosis?
Osteomyelofibrosis (also known as chronic idiopathic myelofibrosis, osteomyelosclerosis, or primary myelofibrosis) is one of the so-called chronic myleoproliferative disorders. These are characterized by overproduction of blood cells by the hematopoietic cells in the bone marrow, called hematopoietic stem cells. In osteomyelofibrosis, leukocytes and platelets in particular are produced in increased numbers in the early phase of the disease. As the disease progresses, this results in the formation of increasingly fibrous connective tissue in the bone marrow, which in the long term leads to obliteration of the hematopoietic bone marrow tissue. Blood formation is shifted to the spleen and liver, which are therefore significantly enlarged. Since these cannot fully compensate for the normal blood formation of the bone marrow, a pronounced anemia (anemia) develops. Osteomyelofibrosis is a very rare disease with an incidence of 0.6 to 1.5 per 100,000 population or 1200 new cases annually. Women are more frequently affected than men. The median age of onset is between 60 and 65 years.
Causes
The causes and etiology of osteomyelofibrosis have not yet been determined. The disease occurs as a primary or idiopathic form independently or secondarily as a consequence of another disease that alters the bone marrow. In primary osteomyelofibrosis, an acquired genetic defect is assumed. Thus, a mutation typical for chronic myeloproliferative diseases – the so-called JAK2 mutation – can be detected in 50 percent of cases. In addition, factors such as exposure to ionizing radiation or chemical substances as well as other, as yet unexplained influencing factors are discussed as possible causes. Underlying diseases of the secondary form are, in particular, essential thrombocythemia (greatly increased multiplication of platelets) and polycythaemia vera (greatly increased formation of new red blood cells).
Symptoms, complaints, and signs
Osteomyelofibrosis is characterized by an insidious onset and slow development of symptoms. Clinically, the disease is manifested by the characteristic triad of highly abnormal connective tissue proliferation (marrow fibrosis) with obliteration of the hematopoietic bone marrow tissue, displaced hematopoiesis in the spleen and liver (extramedullary hematopoiesis), and spleen enlargement (splenomegaly) as a result of displaced hematopoiesis. As a result of the greatly enlarged spleen, adjacent organs, especially intestinal areas, are also displaced. The movement of the intestines (peristalsis) is impeded. Various, sometimes alternating symptoms occur, such as a feeling of pressure in the left upper abdomen, increasing abdominal girth and heartburn. The increase in pressure in the abdomen leads to hernia formation (hernia of the groin, navel or stomach) as well as pressure on the bile duct and blood vessels. The overly enlarged spleen also filters too many blood cells from the peripheral blood (hypersplenism). Since the spleen and liver cannot completely replace the bone marrow, blood cell production is limited as the disease progresses. Both processes lead to a strong decrease of all blood cells (pancytopenia) as well as increased bleeding tendency and susceptibility to infections. In some cases, the liver is also slightly enlarged. General symptoms often include loss of appetite with weight loss, decreased performance, and occasionally fever and night sweats.
Diagnosis and course of the disease
The diagnosis is often made incidentally because of the enlarged and therefore painful spleen or during a routine blood test. Thus, in the early phase, the blood count shows a greatly increased number of white blood cells (leukocytosis) and increased platelet neoplasm (thrombocytosis), whereas the red blood cells (erythrocytes) are mostly normal. In the late phase, pancytopenia, in which blood formation decreases in all three cell series, is detectable in the blood count. In addition, immature precursors of white and red blood cells due to extramedullary hematopoiesis show up in the blood smear (so-called leukoerythroblastic blood count). In addition, the characteristic JAK2 mutation can be detected.The bone marrow puncture, in which no or only very little bone marrow is obtained (so-called punctio sicca or “dry marrow”), is diagnostically decisive. The subsequent fine tissue examination reveals marrow fibrosis. Sonography can assess the enlargement of the spleen and liver. X-ray may show the excessive accumulation of calcareous bone substance (sclerosis) in the spinal region. The course and prognosis of the incurable disease are highly variable and must be evaluated on an individual basis. The prognosis of the primary form is better than that of the secondary form. Overall survival averages five years.
Complications
Osteomyelofibrosis is a malignant disease of the hematopoietic system. However, its prognosis is highly variable. Thus, death can occur at any stage of the disease due to serious complications. However, within the framework of therapy, a significant reduction in the risk of complications is possible. In the early phase of the disease, thromboses often develop, which can lead to embolisms resulting in death. This is caused by a very high division rate of the hematopoietic cells. Later, a strong reduction of the different blood cells dominates, which is called pancytopenia. Blood formation then no longer takes place in the bone marrow, but in the spleen and liver. For this reason, in the late phase of osteomyelofibrosis, there is splenomegaly as well as hepatomegaly. Thus, the spleen and liver become very enlarged. As a complication of splenomegaly, hypersplenism sometimes occurs with constant anemia, increased bleeding tendency, and increased risk of infection. In addition, hypersplenism is very painful because the spleen’s size can displace neighboring organs. If left untreated, this condition sometimes leads to death. Furthermore, a so-called blast relapse can occur in the late stage. This is an aggressive leukemia with a lethal outcome due to the increased formation of immature myolytic and lymphoid blood cells. In addition to leukemia, infections are the most common fatal complications of osteomyelofibrosis.
When should you see a doctor?
People suffering from a general feeling of illness with an increasing tendency should consult a doctor. If there is swelling in the upper body, an increasing abdominal girth or heartburn, a doctor is needed to clarify the symptoms. A decrease in performance, fever, internal weakness and loss of appetite are signs of a health disorder. A visit to the doctor is necessary if there is a feeling of pressure or herniation in the navel or stomach area. Bowel discomfort or a repetitive noise in the gastrointestinal area is considered unusual. A physician should be consulted so that an investigation of the cause can be initiated. Characteristic of osteomyelofibrosis is a slow increase in symptoms and simultaneous decrease in quality of life. The process is described by patients as gradual and takes place over several months. If daily obligations can no longer be fulfilled, participation in social as well as societal life decreases and well-being is reduced, a physician should be informed of the developments. Night sweats, changes in connective tissue, irregularities in heart rhythm, and circulatory problems should be presented to a doctor. If thromboses develop, there is a danger to the life of the affected person. The fastest possible medical care is necessary to prevent permanent damage to health or premature death.
Treatment and therapy
Causal therapy is not possible for osteomyelofibrosis. Because the hematopoietic bone marrow is progressively destroyed, only an allogeneic blood stem cell transplant can cure the disease in the long term. However, this high-risk transplantation is only performed in patients under 60 years of age who do not have any significant concomitant diseases. The chances of success are also lower because the transplanted blood stem cells settle poorly in the obliterated bone marrow. In addition, treatment is exclusively symptomatic. In the early phase, alpha-interferon or hydroxyurea are used to reduce the platelet and leukocyte count with medication. With the help of thalidomide and lenalidomide – possibly in combination with predisolone – the transfusion requirement caused by the anemia is reduced.If the red blood cell and platelet counts are too low, concentrates of red or white blood cells can be added in the late phase (red blood cell or platelet substitution, respectively). With the red cell concentrates, high amounts of iron are supplied to the body. This accumulates in the body and can damage the heart and liver (secondary hemochromatosis). Special drugs can be used to eliminate the excess iron. To stimulate the formation of red blood cells, growth factors such as erythropoietin or, in very rare cases, androgens such as winobanin or metenol are also used. If there is an increased risk of thrombosis as a result of thrombocytosis, ASA (100/dl) or, as a reserve agent, anagrelide is used. Splenectomy (removal of the spleen) is usually performed in the early stage and only in cases of mechanical displacement symptoms and hypersplenism, since replacement blood formation takes place in the spleen. In the late stage, a mild form of radiation may also be indicated for splenic reduction.
Outlook and prognosis
The prognosis of osteomyelofibrosis depends on numerous factors because its course varies widely. These include whether it is primary or secondary, or whether the patent suffers from additional diseases. In primary osteomyelofibrosis, a reduced life expectancy must be expected. Thus, about 50 percent of all affected individuals are expected to live another five years. In 20 percent of all patients, life expectancy is more than ten years. However, the rare disease primarily manifests itself in older people. The most common causes of death in osteomyelofibrosis include cardiovascular failure and infections due to bone marrow weakness. Aggressive acute myeloid leukemia also sometimes occurs. However, the prognosis also depends on the genetic defect underlying the disease. Adverse factors for prognosis include leukocytosis, leukopenia, neoangiogenesis, thrombocytopenia, and severe anemia (anemia). Due to the variability of prognosis, a special risk score exists. This differentiates between four patient risk groups. The score also affects the therapeutic measures. Negative factors for the prognosis are an age of more than 65 years and symptoms such as loss of weight, night sweats and fever. A permanent cure of osteomyelofibrosis is only possible by allogeneic bone marrow transplantation. However, because of its high risks, it is performed only in patients younger than 50 years.
Prevention
Osteomyelofibrosis cannot be prevented.
Follow-up care
In most cases, the person affected by osteomyelofibrosis has very few and usually limited measures of direct aftercare available to him or her. For this reason, the affected person should see a physician very early in the course of this disease to avoid complications or other complaints as it progresses. The earlier a doctor is consulted, the better the further course of the disease usually is. Those affected themselves are usually dependent on taking various medications. Care should always be taken to ensure that the correct dosage is taken and that the medication is taken regularly in order to alleviate the symptoms properly and permanently. Regular checks by a doctor are also very useful and can prevent further damage. Most patients are dependent on the help and support of their own family in their daily lives. Psychological support also has a positive effect on the further course of osteomyelofibrosis and can prevent the development of depression and other psychological complaints. Possibly, the disease also leads to a reduced life expectancy of the affected person, although the further course is very much dependent on the time of diagnosis.
What you can do yourself
In addition to medical treatment, a positive attitude has a favorable effect on the further course of the disease. Talks with a therapist are often a useful support, as mindfulness and calmness are conveyed in many life situations. In order to be able to effectively adapt the therapy with the doctor to one’s own needs, it is advisable to note symptoms such as pain, itching, fatigue, weight loss, etc. on a weekly basis and to show the notes at the next doctor’s appointment.Exercise adapted to one’s own ability helps to reduce stress, strengthens the body and improves general well-being. Traveling can also have this effect, but those affected must always make sure to pack meaningful medical documents so that doctors on site can quickly read up on the case if necessary. In addition, necessary vaccinations must be carried out in time to build up sufficient vaccination protection. A change of diet together with a nutritionist and the accompanying doctor can alleviate problems such as anemia, fatigue and weight problems, and specifically adapted to one’s own needs, can significantly improve the quality of life. This includes a diet rich in nutrients, starch and vitamins as well as sufficient fluid intake. Dividing breakfast, lunch, and dinner into several smaller portions and snacks that are eaten throughout the day allows for greater nutrient intake and associated weight gain, even with a rapid feeling of satiety.
