Myelofibrosis - bone marrow fibrosis - is the rarest of all myeloproliferative neoplasms, i.e. those related to the malfunctioning of the bone marrow. It is a rare and quite difficult to diagnose blood cancer. Symptoms, especially at the beginning of the disease, can indicate many other conditions. What are the causes and symptoms of myelofibrosis? How is the treatment going and what is the prognosis?

What is myelofibrosis?

Myelofibrosis, or bone marrow fibrosis, is a hematological disease from the group of negative BCR-ABL1 myeloproliferative neoplasms - the presence of the BCR-ABL gene is not found in bone marrow or peripheral blood tests. It may develop as a primary disease or appear secondary in people suffering from polycythemia vera and essential thrombocythemia.

The essence of myelofibrosis is the excessive accumulation of collagen deposits in the bone marrow, which in effect displaces the cells of the hematopoietic system and leads to the development of bone marrow failure. The expanding fibers of connective tissue gradually replace blood-producing elements in the marrow. In more advanced stages of myelofibrosis, blood production is transferred to the spleen and then to the liver - which in turn leads to a significant enlargement of these organs.

Myelofibrosis is not common - in Europe every 50,000 people suffer from it. residents. At the time of diagnosis, the mean age of patients is about 65 years - however, in almost 10% of patients. patients are diagnosed with the disease before the age of 45. Myelofibrosis is a gender-independent disease - it attacks men and women with equal frequency. In some patients it is diagnosed at an early stage, while in others it is diagnosed in the advanced stage, which significantly worsens the prognosis and the expected survival time.

Myelofibrosis - symptoms

The symptoms of myelofibrosis depend on the stage of the disease. In the initial phase of myelofibrosis, the so-called in the pre-fibrotic (prefibrotic) phase, the disease does not show any symptoms, also in blood tests - blood count is usually normal, sometimes only an increased number of white blood cells is found, some patients may have mild anemia or thrombocythemia. The spleen is usually normal (sometimes slightly enlarged).

Until symptomatic developmentMyelofibrosis occurs with the progression of bone marrow fibrosis. Then, general symptoms appear, which may indicate many other diseases - some patients are initially treated for anemia.

General symptoms of myelofibrosis:

  • fatigue
  • weakness
  • shortness of breath during exercise
  • palpitations
  • flatulence
  • feeling of fullness in the stomach
  • night sweats
  • enlarged spleen and liver
  • itchy skin
  • changes in blood count.

Most patients have general symptoms at diagnosis, such as weight loss, fatigue, night sweats, and itchy skin. Pressing the spleen on the intestines and stomach causes abdominal pain, a feeling of pressure in the abdominal cavity. Some patients may also develop peritonitis and spleen infarction, which is manifested by severe pain in the area of ​​the left hypochondrium and high fever.

- The patient then complains of a feeling of fullness and abdominal pain, and his daily functioning is difficult. An enlarged spleen can fill the left side of the abdomen and cause a feeling of fullness and pain in the left hypochondrium. While in a he althy person it weighs about 150 grams, in patients with myelofibrosis it can reach a weight of up to 10 kg and as much as 30 cm in length - says Prof. dr hab. n. med. Joanna Góra-Tybor, head of the Hematooncology Department at the M. Kopernika, Department of Hematology, Medical University of Lodz.

Some patients also have an enlarged liver.

Myelofibrosis - causes

So far, the causative agents of the disease have not been identified, but it is known that JAK2 gene mutations in bone marrow stem cells, as well as MPL and CALR mutations play an important role in its development.

These mutations cause abnormal cells to multiply uncontrollably in the bone marrow. Interestingly, even in 15 percent. neither of these mutations is found in patients. Apart from them, epigenetic factors also play an important role in the development of the disease.

Myelofibrosis - research and diagnosis

The diagnosis of myelofibrosis is difficult. Typical for palpation is splenomegaly, i.e. an enlarged spleen (in the advanced stage of the disease, it can reach very large sizes, even reaching the pubic symphysis).

The key to detecting myelofibrosis is primarily an interview conducted by a family doctor, as well as the patient's examination, especially abdominal examination. Palpable enlarged spleen and / or liver may direct the diagnosis towards myelofibrosis.

A patient suspected of having myelofibrosis shouldbe referred to a hematologist as soon as possible for further diagnosis and treatment.

A doctor suspecting myelofibrosis should order a morphology with a microscopic examination, as well as an ultrasound of the abdominal cavity and a bone marrow examination from the hip bone (trepanobiopsy).

Molecular blood or bone marrow tests for disease-specific gene mutations, including JAK2 V617F, MPL, and CARL, as well as tests for the presence of the BCR-ABL1 gene, are also required to rule out chronic myeloid leukemia.

In the case of myelofibrosis, anemia is visible in the blood count, and the blood smear shows a leucoerythroblastic reaction (i.e. the early development stages of white and red blood cells, so-called blasts and eryrtoblasts, which are not normally present in the blood), as well as giant platelets and tear-shaped red blood cells.

The diagnosis is based on the histopathological examination of the bone marrow, on the basis of which the doctor can assess its appearance, fibrosis and its stage.

Treatment of myelofibrosis

Patients with myelofibrosis can only be cured by allogeneic hematopoietic stem cell transplantation - that is, bone marrow transplantation. However, this method is not suitable for everyone: due to the high mortality associated with the period before and after transplantation, it is used in patients at an advanced stage of the disease. The remaining patients are treated with life-extending medications that alleviate the symptoms of the disease and its effects.

The choice of treatment method depends on the stage of the disease, and therefore its stage.

In the case of the pre-fibrotic phase of the disease, it is usually necessary to take medications that normalize the level of platelets and white blood cells in order to avoid thrombosis, and also to slow the progression of the disease. Patients are prescribed cytostatic drugs or alpha interferon.

Patients from low and intermediate-1 risk groups receive treatment depending on the symptoms of the disease - e.g. in anemia, androgenic drugs or glucocorticosteroids are prescribed.

Symptomatic treatment is applied in patients from intermediate-2 and high risk group. A new drug containing the active substance ruxolitinib is used in patients in this group eligible for bone marrow transplantation (i.e. people under the age of 70 without serious chronic diseases) and in the chronic treatment of patients in this group - it works by blocking the JAK signaling pathway. -STAT and the ability to multiply cells, reducing the size of the spleen and relieving general symptomsdiseases, e.g. night sweats or itchy skin.

In rare cases, people with severely enlarged spleen who do not respond to treatment also use other treatments, including surgical removal of the spleen (splenectomy) or radiotherapy of the spleen.

Category:

Oncology