Myelodysplastic syndrome is a wide spectrum of pathologies that unites a single pathogenetic mechanism of development, consisting of a combination of dysplastic changes in the bone marrow and cytopenia in a circulating blood. Each of the diseases, accompanied by the development of myelodysplastic syndrome, creates an increased risk of developing acute myeloblastic leukemia.
Recently, the problem of myelodysplastic syndrome has been given to a huge number of scientific works, since the incidence rate of this pathology has increased significantly, and generally accepted effective therapy has not yet been developed. In addition, there is an increase in the incidence of primary myelodysplastic syndrome, which affects young people, which is explained by the significant deterioration of the ecological situation.
The risk group for the development of myelodysplastic syndrome is mainly elderly patients.
Myelodysplastic syndrome in children is an exception to the rule, since early detection of this condition is extremely difficult.
Causes of Myelodysplastic Syndrome
The predominant majority of cases of myelodysplastic syndrome belongs to the category of idiopathic etiopathogenetic variant, in which it is not possible to determine the exact cause of its development. Secondary myelodysplastic syndrome occurs exclusively among oncological patients, and the debut of its development falls on the period after the application of chemotherapy. This category of patients is characterized by extremely aggressive course of the myelodysplastic syndrome, as well as resistance to drug therapy. Drugs that are used in the treatment of cancer (Cyclophosphamide, Topotecan) have a damaging effect on the genome, which provokes the development of myelodysplastic syndrome.
There is a wide range of modifiable risk factors, eliminating which, it is possible to avoid the development of myelodysplastic syndrome, which include smoking, exposure to ionizing radiation and benzene vapor.
Most oncologists hold the opinion that the main background for the development of acute leukemia is myelodysplastic syndrome. Refractory anemia is the most common form of myelodysplastic syndrome and many specialists in practical activity identify these concepts. The principal difference between refractory anemia and the classical variant of reducing hemoglobin concentration in the blood is that, in the myelodysplastic syndrome, a large number of blast cells accumulate in the bone marrow of the patient, accounting for up to 30% of the total cellular composition.
In the development of myelodysplastic syndrome, the importance of cell production in the bone marrow is important. Due to the organic and morphological changes in the bone marrow, the compensatory mechanisms of extramedullary hemopoiesis, accompanied by hepatosplenomegaly , develop in the patient's body. The pathogenetic basis of the myelodysplastic syndrome is a violation of the proliferation and maturation of blood cells at the bone marrow level, resulting in a large number of blast cells possessing all the signs of malignancy.
Symptoms of Myelodysplastic Syndrome
The clinical manifestations of the myelodysplastic syndrome directly depend on the degree of myelopoiesis damage, therefore at the initial stage of the disease the patient has an asymptomatic period that can last quite a long time. In a situation in which the patient has a myelodysplastic syndrome due to a predominant anemia symptom complex, he has an increased weakness, marked pallor of visible skin, and lack of appetite.
Increased predisposition to diseases of infectious nature indicates neutropenia . In addition, this category of patients has an increased risk of developing complications of an inflammatory nature. However, the thrombocytopenic component of the myelodysplastic syndrome, which manifests itself in the development of the hemorrhagic symptom complex in the form of increased bleeding, frequent episodes of epistaxis and the development of petechial elements of the rash on the skin, is the most difficult with regard to the patient's well-being.
Qualitative diagnosis of myelodysplastic syndrome should include an assessment of the intensity of clinical manifestations, as well as changes in the parameters of the cellular composition of not only peripheral blood, but also bone marrow aspirate. So, if there are signs of refractory anemia, leukocytopenia or thrombocytopenia , and also in the combination of these disorders in elderly people, it is necessary to assume the presence of a myelodysplastic syndrome.
Refractory anemia is characterized by a combination with anisocytosis and macrocytosis, which is manifested in an increase in the average volume of cells of the erythrocyte series. Thrombocytopenia in myelodysplastic syndrome most often does not reach critical values, but is accompanied by a change in the size of platelets, as well as a decrease in their granularity. Not necessarily with myelodysplastic syndrome, there should be a decrease in the white blood cell count. A more specific criterion is the change in leukocyte cytoplasmic granularity with the presence of pseudopelgerian cells. An increase in the concentration of monocytic blood cells is indicative of the development of myelomonocytic-type chronic leukemia.
Highly accurate diagnostic methods, which have almost 100% certainty, are immunophenotyping, as well as cytochemical analysis of bone marrow aspirate, which makes it possible to determine specific enzymes characteristic exclusively for blast cells.
Treatment of myelodysplastic syndrome
The decision regarding the choice of tactics for managing the patient with myelodysplastic syndrome largely depends on the severity of laboratory manifestations. Thus, the absence of signs of hemorrhagic syndrome, severe anemia, as well as a high risk of developing complications of an infectious nature is the basis for the use of expectant management in relation to the patient. In this situation, only dynamic monitoring of laboratory criteria for hemo- and myelopoiesis is shown.
The use of therapeutic techniques for the correction of myelodysplastic syndrome is justified only in the case of severe clinical manifestations, as well as an increased risk of transformation into leukemia . As therapeutic measures in the myelodysplastic syndrome, both conservative and surgical techniques are used.
The most common was the so-called accompanying replacement therapy, which implies intravenous injection of blood components in the form of erythrocyte mass or thromboconcentrate. It should be borne in mind that prolonged therapy with the use of hemocomponents inevitably provokes supersaturation of the patient's body with iron, which in an increased concentration has a toxic effect on all organs and structures, causing a violation of their function. Given this feature, blood transfusion should be combined with the use of drugs that bind iron and promote its elimination from the body (Desferal in a daily dose of 20 mg per 1 kg of the patient's weight parenterally).
Parenteral administration of erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor is used as an additional symptomatic therapy and does not affect the patient's life expectancy in any way, which in this situation is a priority indicator of the effectiveness of myelodysplastic syndrome treatment.
The presence in the patient of refractory anemia, as one of the components of the myelodysplastic syndrome, is the justification for the use of immunosuppressive therapy (Lalalipomide in a daily dose of 25 mg).
A drug with proven effectiveness in preventing the development of leukemia in the myelodysplastic syndrome is Azacitidine, the use of which is done according to a certain scheme. The first course of therapy lasts seven days, during which the patient is intravenously administered Azazitidine at a daily dose of 75 mg / m2. During the subsequent cycles of therapy, the daily dose for the patient is calculated in a ratio of 100 mg / m2. Multiplicity of course therapy is one week each month. It should be borne in mind that the effect of using Azacitidine can be very intense, and therefore, every intake of the drug should be preceded by a study of a clinical blood test. Assessment of hematologic changes should be made after the administration of the drug. Absolute contraindication for the use of Azacitidine is the patient's presence of severe organic pathology of the liver and kidneys, since the drugs of this pharmacological group are highly hepatotoxic. Due to the fact that metabolic products in the decay of Azacitidine are eliminated with the excretory function of the kidneys, conditions are created for toxic damage to these structures, therefore, the drug should be administered under the dynamic control of creatinine and urea in the blood, as the main markers of kidney failure.
Despite the positive results of the medical correction of myelodysplastic syndrome, the only pathogenetically substantiated treatment that allows complete remission to be achieved in 95% of cases is the allogeneic transplantation of the stem hemopoietic cell substrate, however the category of patients of this method is the age of 55 years, which limits it application. These restrictions are due to the fact that in old age patients are severely suffering from chemotherapy, which is mandatory as a preparation of the patient for transplantation. In addition, it should be borne in mind that in 10% of cases after transplantation graft rejection may develop, which is life threatening for the patient. Recently, transplantation of stem cells, taken not from bone marrow, but from circulating peripheral blood, has been used successfully enough.
Myelodysplastic syndrome prognosis
To a greater extent, the prognosis with one or another type of myelodysplastic syndrome depends on the pathogenetic variant of the course of this pathology, as well as on the presence or absence of severe complications.
Recent scientific research in hematology was devoted to the development of criteria for estimating the prognosis for the life of patients suffering from myelodysplastic syndrome. In practice, hematologists and transfusiologists use the international classification of IPSS, according to which three main risk groups are identified (low, intermediate and high). The main parameters in the evaluation of the prognosis for myelodysplastic syndrome are the percentage of blast cells in the bone marrow, the profile of chromosomal abnormalities, and the severity of cytopenia. The most favorable course is observed in patients who have 0 points in the IPSS classification. The average life expectancy at high risk for this classification is no more than 6 months.
? Myelodysplastic syndrome - which doctor will help ? If there is or suspected development of myelodysplastic syndrome, you should immediately seek advice from such doctors as a hematologist, blood transfusion therapist, immunologist and oncologist.