Primary myelofibrosis
There are diseases that everyone hears about, they warn us about them from the screens, talk about treatment, but we know almost nothing about some, so we notice them late. Primary myelofibrosis is one of those

What is myelofibrosis

Primary myelofibrosis is a rather rare disease that affects the human hematopoietic system and its most important part, the bone marrow. This is a spongy tissue in the bones that produces blood cells. At first, these are stem cells, but in the bone marrow they get “specialized” – they turn into red blood cells, white blood cells and platelets. The former are responsible for carrying oxygen to the tissues of the body, the latter are responsible for fighting infections, and the third help the blood to clot.

With myelofibrosis, the program by which the stem cell works is disrupted. As a result, “wrong” blood cells are formed, they differ from normal ones both in shape and in properties. There are more and more of them, and they begin to influence the formation of normal cells: the number of erythrocytes decreases – anemia occurs, the number of platelets falls – bleeding appears, the number of leukocytes increases. The disease progresses, and fibrosis develops in the bone marrow – the spongy layer is covered with scars. In this case, tumor blood cells begin to be produced in the spleen and liver, which causes these organs to increase in size.

Symptoms of primary myelofibrosis

It is not easy to suspect primary myelofibrosis itself – its initial symptoms are quite common, they are easy to confuse with manifestations of other ailments.

Common symptoms of primary myelofibrosis include:

  • fatigue;
  • pallor;
  • decreased appetite;
  • itching;
  • sweating;
  • weight loss;
  • feeling of heaviness in the left hypochondrium.

Less often, patients come to the hematologist because of fever or jaundice. In some cases, the disease is manifested by increased bleeding: there is blood from the nose, gums.

In 5% of cases, the patient may not experience discomfort at all, and the disease is discovered by chance, noticing an enlarged spleen.

Enlargement of the spleen (splenomegaly) and liver (hepatomegaly) sometimes makes itself felt in the form of pain or discomfort in the hypochondrium – left or right depends on the enlarged organ.

Quite often, primary myelofibrosis is recognized by its complications. For example, for anemia, which occurs when the level of hemoglobin in the blood decreases (due to a decrease in the number of red blood cells). In this case, a person experiences constant fatigue, he is lethargic and lethargic. If the anemia has gone far, then the patient feels difficulty in breathing, rapid heartbeat, his skin is paler than usual.

With myelofibrosis, the number of not only red blood cells, but also platelets decreases, then thrombocytopenia develops. Patients suffering from it are more likely to get bruises even at the slightest blow. Often they experience spontaneous bleeding from the nose and gums.

In some patients with primary myelofibrosis, the number of platelets may, on the contrary, increase, thrombocytosis will develop. In this case, the blood will become more viscous, clots will begin to appear in the vessels that interfere with blood flow. This condition can manifest itself in swelling of the limbs, their soreness.

We have not yet said anything about white blood cells, and with myelofibrosis their number may drop. This is manifested in the fact that patients get sick more often, they now and then have a cough, sore throat, runny nose, skin infections.

Diagnostics

The diagnosis of primary myelofibrosis is based on a series of laboratory tests and procedures. The most basic diagnostic method is a clinical blood test. It allows you to determine the amount of hemoglobin, platelets and leukocytes in the blood. In addition, it will show if there are young forms of leukocytes and blasts in the blood – immature blood cells,

The doctor may also order a biochemical blood test. It will provide an opportunity to evaluate the work of internal organs (liver, kidneys), show the deficiency of substances necessary for hematopoiesis and the level of iron.

The most reliable way to check if a person has myelofibrosis is to take a bone marrow biopsy. It can be used to determine the number of immature cells in the bone marrow. If there are 20% or more blasts, then myelofibrosis has developed into acute myeloblastic leukemia.

The procedure for obtaining bone marrow is called a trephine biopsy. The doctor first anesthetizes the area of ​​the body with a thin needle, and then inserts a larger needle with a lumen to obtain a column of bone material. During the sampling of the brain, the patient may experience pain, which sometimes scares people. Therefore, doctors advise taking painkillers or sedatives in advance.

A test for the presence of the BCR-ABL1 gene is also prescribed for patients with suspected primary myelofibrosis, the purpose of this test is to exclude another blood disease – chronic myelogenous leukemia. Their manifestations are similar, but the treatment should be completely different.

A cytogenetic study of the bone marrow is carried out in order to detect chromosomal abnormalities, and a molecular genetic study for the presence of JAK2, CALR, MPL mutations will tell you exactly if there is a diagnosis of myelofibrosis. An ultrasound examination of the abdominal organs will not hurt either, it will show whether the spleen and liver are normal.

Complications

Complications can develop in primary myelofibrosis. The most common of them are tumor intoxication, splenomegaly (an increase in the spleen), anemia (a drop in hemoglobin), infectious complications, thrombocytopenia (a decrease in the number of platelets and, as a result, bleeding) and hemorrhagic syndrome (spontaneous bleeding), thrombosis, uric acid diathesis (secondary gout). ) and secondary hemosiderosis (accumulation of iron in organs and tissues).

A formidable complication is the transformation of the disease into acute leukemia, which requires the appointment of a completely different therapy.

Therapies

There are several methods of treatment for primary myelofibrosis: medication, allogeneic bone marrow transplantation, surgical treatment, radiation therapy, and hemocomponent therapy.

The choice of treatment option lies with the attending physician. In the case of primary myelofibrosis, this is a hematologist or oncologist. The choice of therapy is based on several factors. First, based on the tests, the doctor determines the patient in the risk group from 1st to 4th. Secondly, he assesses the severity of the symptoms of the disease. Thirdly, the age of the patient and, finally, the availability of bone marrow donors and the possibility of transplantation.

Patients who are at low risk and do not suffer from symptoms of the disease are most often not even prescribed drug therapy. The rest are prescribed first.

Radical treatment is allogeneic bone marrow transplant. In fact, it allows you to completely replace the human immune system. The new immunity will kill the foreign myelofibrosis cells.

However, this method has a number of limitations:

  • age less than 65 years;
  • the presence of severe concomitant diseases of internal organs (cardiovascular, respiratory systems);
  • irreversible changes in the bone marrow at the time of diagnosis of the disease;
  • difficulties in finding a compatible donor.

If the first three points are not about you, then ask them to refer you or your loved ones – brothers, sisters – to tests that will determine whether they are suitable for you as a bone marrow donor. A compatible donor can also be found in the international bone marrow donor registry.

Surgical treatment involves the removal of the spleen (splenectomy). The operation is indicated in cases where the enlargement of the spleen causes pain and begins to cause complications. However, the operation also has certain risks, in patients after splenectomy, an enlarged liver and an increase in the number of platelets are sometimes observed.

Radiation therapy helps shrink the spleen if surgery is contraindicated.

Periodic blood transfusions also help to increase the number of red blood cells and relieve the symptoms of anemia – fatigue, lethargy.

Prevention of primary myelofibrosis

There is no cure for primary myelofibrosis. Patients often come to a hematologist 3-5 years after the onset of the disease, with already developed complications, so the main advice of doctors is to pay attention to your health. If you undergo medical examinations in time, carefully monitor the manifestations of anemia, weakness, weight loss and look for their cause, you can identify myelofibrosis in a timely manner and begin treatment before complications develop.

Popular questions and answers

Why does primary myelofibrosis develop? Can this be prevented?
The causes of primary myelofibrosis are still not fully known. We know that mutations in the genes lead to this disease, but what causes it? Whether smoking, alcohol, radiation can cause a breakdown is not clear. It is generally accepted that certain factors influence the development of primary myelofibrosis, these are age (more often in people over 50), the presence of another blood cell disease (essential thrombocythemia or polycythemia), exposure to certain chemicals (for example, toluene and benzene), radiation.
If I have primary myelofibrosis, is there any chance that I will pass it on to my child?
Primary myelofibrosis is not inherited. Another thing is that there is a hereditary predisposition to the development of tumors. It is possible in first-line relatives (brothers, sisters, children) who are sick with polycythemia vera, primary myelofibrosis, or essential thrombocythemia.
Is it possible to predict how aggressively the disease will develop?
There are a number of signs that suggest that myelofibrosis will develop aggressively and can provoke complications. You are at risk if you have the following test results:

● level of leukocytes 25×109/l and more;

● anemia, hemoglobin less than 100 g/l;

● blasts in peripheral blood;

● platelet count less than 100×109/l.

If, in addition, your age is 65 or older, then you are at high risk.

What are the stages?
There is an early, or pre-fibrous, and fibrous stage of the disease. The transformation of the first into the second is observed in 65% of patients for about four years. At the same time, doctors note that the prefibrotic stage of PMF may persist without progression to the fibrous stage for 10 years or more.

There are also two phases, reflecting the degree of progression of the disease:

● chronic;

● terminal phase of blast transformation – blast crisis.

The chronic phase is characterized by changes in the blood test, an increase in the size of the liver and spleen, the presence of symptoms of tumor intoxication (fever, weight loss, sweating). The blast crisis is the terminal stage of the development of the pathological process. This stage is distinguished by the presence of more than 20% of blast cells in the peripheral blood or in the bone marrow.

What is the life expectancy?
Primary myelofibrosis is not a sentence; you can live with this disease for quite a long time. The life expectancy of the patient depends on how soon the disease is detected and what therapy the doctor prescribes. Of course, the behavior of the patient himself is also important, how seriously he takes the doctor’s recommendations. If the disease is “caught” at an early stage and the disease does not behave aggressively, does not progress, the patient can live for decades. If the disease is detected already at the stage of complications, the prognosis is less positive – on average from a year to 5 years.

Depending on the stage and form of the disease, the optimal treatment tactics is chosen: observation, drug therapy or bone marrow transplantation. The latter is a chance to completely get rid of the disease, other options help to significantly improve the quality of life of the patient and control the disease.

Is there a disability?
The decision on the disability group is made by the employees of the Bureau of Medical and Social Expertise, depending on the complications of the disease. There is no universal indication here. The decision for each patient is made individually. But we can definitely say that a disability is received by a patient who has severe disorders against the background of the underlying disease, who needs regular blood transfusions and has a history of thrombotic complications (heart attack, stroke, thrombosis) that developed against the background of myelofibrosis, hematologists explain.

Expert Commentary

Hematologist, Doctor of Medical Sciences, Professor Bulat Bakirov:

– The initial manifestations of myelofibrosis are not specific and do not immediately suspect the disease. The onset of the disease is usually manifested by weakness, fatigue with little physical exertion, pale skin and weight loss. As the disease develops, pain may appear in the left hypochondrium, due to the growth of the spleen, the stomach may increase, shortness of breath may appear due to the pressure of the spleen on the diaphragm, a person may notice that he has become satiated faster with a small amount of food due to compression of the stomach by the spleen. Often, people do not notice these symptoms, and they begin to worry even when complications develop.

The main complications of myelofibrosis are thrombotic complications in the form of strokes, heart attacks, and thrombosis. In the worst case, it can develop into acute leukemia. The diagnosis is made on the basis of a complete blood count, JAK-2 and CALR mutation analysis, abdominal ultrasound, and bone marrow trephine biopsy. The first three types of examinations are available on an outpatient basis, and trepanobiopsy is performed by a hematologist. If the disease is detected early and the necessary therapy is started, a person can live with it for quite a long time. But, of course, much depends on the adherence to therapy, that is, how the patient follows the doctor’s recommendations and keeps the regularity of taking medications.

Currently, pathogenetic therapy is considered to be the appointment of a drug that acts on the JAK-2 mutation.

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