Osteomyelofibrosis is a very rare, chronic and incurable disease of the bone marrow. It is accompanied by an increasing restriction of blood cell formation, which leads to various complications such as anemia, bleeding and an increased risk of infection.
What is Osteomyelofibrosis?
Osteomyelofibrosis (also chronic idiopathic myelofibrosis, osteomyelosclerosis or primary myelofibrosis) is one of the so-called chronic myleoproliferative diseases. These are characterized by an overproduction of blood cells by the blood-forming cells in the bone marrow, the so-called hematopoietic stem cells. See theinternetfaqs for HFD Basics.
In osteomyelofibrosis, leukocytes and thrombocytes in particular are increasingly produced in the early phase of the disease. As the disease progresses, connective tissue that is rich in fibers increasingly forms in the bone marrow, which in the long term results in the destruction of the blood-forming 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 in the bone marrow, a pronounced anemia develops. Osteomyelofibrosis is a very rare disease with an incidence of 0.6 to 1.5 per 100,000 inhabitants or 1,200 new cases per year. Women are affected more often than men. The mean age at onset is between 60 and 65 years.
The causes and etiology of osteomyelofibrosis have not yet been clarified. The disease occurs as a primary or idiopathic form on its own or secondary to another disease affecting the bone marrow. In the case of primary osteomyelofibrosis, an acquired genetic defect is assumed.
In 50 percent of cases, a mutation typical of chronic myeloproliferative diseases – the so-called JAK2 mutation – can be detected. In addition, factors such as exposure to ionizing radiation or chemical substances as well as other influencing factors that have not yet been clarified are discussed as possible causes.
Underlying diseases of the secondary form are, in particular, essential thrombocythemia (greatly increased proliferation of blood platelets) and polycythemia vera (greatly increased formation of red blood cells).
Symptoms, Ailments & Signs
Osteomyelofibrosis is characterized by an insidious onset and slow development of symptoms. Clinically, the disease manifests itself in the characteristic triad of high-grade abnormal connective tissue proliferation (marrow fibrosis) with obliteration of the blood-forming bone marrow tissue, displaced blood formation in the spleen and liver (extramedullary hematopoiesis) and spleen enlargement (splenomegaly) as a result of the displaced blood formation.
As a result of the greatly enlarged spleen, adjacent organs, especially the intestinal areas, are also displaced. The intestinal movement (peristalsis) is impeded. There are different, sometimes changing symptoms such as a feeling of pressure in the left upper abdomen, increasing abdominal circumference and heartburn. The increase in pressure in the abdomen leads to hernias (hernias of the groin, navel or stomach) and pressure on the bile duct and blood vessels.
The excessively 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 formation is restricted as the disease progresses. Both processes lead to a severe decrease in all blood cells (pancytopenia) as well as an increased tendency to bleed and susceptibility to infection. In some cases, the liver is also slightly enlarged. General symptoms are often loss of appetite with weight loss, reduction in performance and occasionally fever and night sweats.
Diagnosis & course of disease
Diagnosis is often incidental due to the enlarged and therefore painful spleen or during a routine blood test. The blood count in the early phase shows a greatly increased number of white blood cells (leucocytosis) and increased formation of new blood platelets (thrombocytosis), while the red blood cells (erythrocytes) are mostly normal.
In the late phase, pancytopenia, in which blood formation decreases in all three cell lines, can be detected in the blood count. In addition, immature precursors of white and red blood cells appear in the blood smear as a result of extramedullary blood formation (so-called leukoerythroblastic blood count). In addition, the characteristic JAK2 mutation can be detected.
The bone marrow puncture, in which little or no bone marrow can be obtained (so-called punctio sicca or “dry marrow”), is diagnostically decisive. The subsequent histological examination shows the marrow fibrosis. The enlargement of the spleen and liver can be assessed by sonography.
The X-ray image may show excessive accumulation of calcareous bone substance (sclerotherapy) in the spinal column area. The course and prognosis of the incurable disease are very variable and must be assessed individually. The prognosis of the primary form is better than that of the secondary. Overall, the average survival time is five years.
Osteomyelofibrosis is a malignant disease of the hematopoietic system. However, their prognosis is very different. Thus, death can occur at any stage of the disease due to serious complications. However, as part of the therapy, a significant reduction in the risk of complications is possible. In the early phase of the disease, thrombosis often develops, which can lead to embolism and death.
This is caused by a very high rate of division of blood-forming cells. Later, a severe reduction in the various blood cells dominates, which is referred to as pancytopenia. Blood formation then no longer takes place in the bone marrow, but in the spleen and liver. For this reason, splenomegaly and hepatomegaly occur in the late phase of osteomyelofibrosis. So the spleen and the liver enlarge very much.
A complication of splenomegaly is sometimes hypersplenism with constant anemia, increased bleeding tendency and increased risk of infections. In addition, hypersplenism is very painful because the spleen can crowd out the neighboring organs due to its size. Left untreated, this condition sometimes leads to death. Furthermore, a so-called blast surge can occur in the late stage.
This leads to an aggressive leukemia with a fatal outcome due to the increased formation of immature myolytic and lymphatic blood cells. In addition to leukemia, infections are the most common fatal complications of osteomyelofibrosis.
When should you go to the doctor?
People suffering from general malaise with a tendency to increase 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, inner weakness and loss of appetite are signs of a health disorder. A doctor’s visit is necessary if there is a feeling of pressure or a hernia in the area of the navel or stomach.
Intestinal problems or repeated noises in the gastrointestinal area are considered unusual. A doctor should be consulted so that the cause can be investigated. Osteomyelofibrosis is characterized by a slow increase in symptoms and a simultaneous decrease in quality of life. The process is described by the patients as insidious and takes place over several months. If everyday obligations can no longer be fulfilled, participation in social and community life decreases and well-being is reduced, a doctor must be informed of the developments.
Night sweats, changes in the connective tissue, irregular heart rhythm and circulatory disorders must be presented to a doctor. If thrombosis develops, there is a risk of death for the person concerned. It is necessary to receive medical care as quickly as possible so that there is no permanent damage to health or premature death.
Treatment & Therapy
A causal therapy is not possible for osteomyelofibrosis. Since the blood-forming bone marrow is increasingly being destroyed, only an allogeneic blood stem cell transplant can cure the disease in the long term. However, the transplantation, which is associated with a high risk, is only carried out in people under the age of 60 who have no significant comorbidities.
The chances of success are also lower, since the transplanted blood stem cells settle poorly in the bone marrow that has been destroyed. In addition, only symptomatic treatment is given. In the early phase, alpha interferon or hydroxyurea are used to reduce the number of thrombocytes and leukocytes by medication.
With the help of thalidomide and lenalidomide – possibly in combination with predisolone – the need for transfusions caused by anemia is reduced. If the number of erythrocytes and thrombocytes is too low, concentrates of red or white blood cells can be administered in the late phase (erythrocyte or thrombocyte substitution). High amounts of iron are supplied to the body with the erythrocyte concentrates.
This accumulates in the body and can damage the heart and liver (secondary haemochromatosis). Excess iron can be flushed out with special medication. In order to stimulate the formation of red blood cells, growth factors such as erythropoietin or, in very rare cases, androgens such as winobanine or metenol are also used.
If there is an increased risk of thrombosis as a result of thrombocytosis, ASA (100/dl) or anagrelide as a reserve agent is used. A splenectomy (removal of the spleen) is usually carried out in the early stages and only in the case of mechanical displacement symptoms and hypersplenism, since the replacement blood formation takes place in the spleen. In the late stages, a mild form of radiation to reduce the size of the spleen may also be indicated.
Outlook & Forecast
The prognosis of osteomyelofibrosis depends on numerous factors because it varies greatly. This includes whether the condition is primary or secondary, or whether the patent suffers from additional diseases.
In the case of primary osteomyelofibrosis, a reduced life expectancy must be expected. Around 50 percent of all affected people are expected to live another five years. In 20 percent of all patients, the life expectancy is more than ten years. However, the rare disease primarily occurs in older people. The most common causes of death from osteomyelofibrosis include cardiovascular failure and infections due to bone marrow weakness. Aggressive acute myeloid leukemia sometimes occurs. However, the prognosis also depends on the genetic defect underlying the disease. Leukocytosis, leukopenia are considered unfavorable factors for the prognosis, neoangiogenesis, thrombocytopenia and severe anemia.
Due to the difference in the prognosis, there is a special risk score. This differentiates between four patient risk groups. The evaluation also affects the therapeutic measures. An age of over 65 years and symptoms such as weight loss, night sweats and fever are considered negative factors for the prognosis.
Permanent healing of osteomyelofibrosis is only possible through allogeneic bone marrow transplantation. However, because of its high risks, it is only performed on patients under the age of 50.
Osteomyelofibrosis cannot be prevented.
In most cases, those affected with osteomyelofibrosis have only very few and usually only limited direct follow-up measures available. For this reason, those affected by this disease should see a doctor very early on, so that there are no complications or other symptoms as the disease progresses. The sooner a doctor is consulted, the better the further course of the disease.
Those affected are usually dependent on taking various medications. You should always pay attention to the correct dosage and regular intake in order to relieve the symptoms properly and permanently. Regular check-ups by a doctor are also very useful and can prevent further damage.
Most patients depend on the help and support of their own family in their everyday life. Psychological support also has a positive effect on the further course of osteomyelofibrosis and can prevent the development of depression and other psychological complaints. The disease may also lead to a reduced life expectancy for those affected, with the further course depending very much on the time of diagnosis.
You can do that yourself
In addition to medical treatment, a positive attitude has a beneficial effect on the further course of the disease. Discussions with a therapist are often a useful support, as mindfulness and calm are conveyed in many life situations.
In order to be able to effectively adapt the therapy to your own needs at the doctor’s, it is advisable to note down symptoms such as pain, itching, tiredness, weight loss etc. on a weekly basis and to show the notes at the next doctor’s appointment.
Sporting activity adapted to your own performance helps to reduce stress, strengthens the body and improves general well-being. Traveling can also have this effect, but those affected must always take care to pack meaningful medical documents so that local doctors can quickly read into the case if necessary. In addition, necessary vaccinations must be carried out in good time in order to build up sufficient vaccination protection.
A change in diet together with a nutritionist and the accompanying doctor can reduce problems such as anemia, tiredness and weight problems and, specially adapted to your own needs, significantly increase 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 a higher nutrient intake and associated weight gain, even if you feel full quickly.