Myelodysplastic syndrome refers to a group of hematological pathologies that are caused by impaired reproduction of one or more blood cells, for example, red blood cells, platelets or white blood cells in the bone marrow. Consider this disease in detail, find out its main causes, symptoms and find out what treatment is like.
Disease Description
Myelodysplastic syndrome involves a fairly wide range of pathologies, combining a single pathogenetic mechanism, which consists in a combination of dysplastic changes in cytopenia and bone marrow in the circulating blood. Each of the pathologies accompanied by the appearance of this syndrome causes an increased risk of acute myeloid leukemia.
Recently, a huge amount of scientific work has been devoted to the phenomenon of myelodysplastic syndrome (refractory anemia), since the actual incidence rate of this disease has increased significantly, and generally accepted effective therapy has not yet been developed. In addition, experts note an increase in the incidence of the primary form of pathology, which can affect people at a young age, which can be explained by a significant deterioration in the environmental ecological situation in the modern world.
It should be noted that the main risk group, in which the development of myelodysplastic syndrome is most likely, is mainly elderly patients. Among the children, he appears to be the exception to the rule, since such an early detection of such a condition is extremely difficult. Next, we consider the main reasons for the development of this pathology.
Main reasons
Most examples of the syndrome can be attributed to the category of idiopathic etiopathogenetic form, in which it is not possible to accurately determine the main cause of its development. The secondary form of myelodysplastic syndrome occurs exclusively in patients with an oncological profile, and the debut of its formation falls, as a rule, on the period following the use of chemotherapy. In this category of patients, the syndrome is extremely aggressive, in addition, it is particularly resistant to drug therapy. Drugs used in the treatment of oncological pathologies, for example, Cyclophosphamide with Topotecan, have a damaging effect on the genome, thereby provoking the development of myelodysplastic syndrome (reflex anemia).
There is a fairly wide range of main causes of risk, eliminating which, it will be possible to avoid the formation of pathology. These include smoking with exposure to ionizing radiation, benzene vapor.
Most oncologists are of the opinion that this syndrome serves as the main background for the development of acute leukemia. Refractory anemia is the most common form of this disease and many experts in practical activities identify these concepts. The main difference between refractory anemia and the standard classical variant of lowering the hemoglobin concentration in the blood is that, against the background of a syndrome with an excess of blasts, a large number of so-called blast cells can accumulate in the patient’s bone marrow, which comprise up to thirty percent of the total cellular composition.
In the development of the pathogenesis of myelodysplastic syndrome, the efficiency of cell production in the bone marrow is of great importance. As a result of organic, morphological changes in the bone marrow, the compensatory mechanisms of the extramedullary form of hematopoiesis may develop in the patient’s body. A similar phenomenon is accompanied in addition by hepatosplenomegaly.
The pathogenetic basis of secondary myelodysplastic syndrome consists of a violation of proliferation, maturation of blood cells within the bone marrow, resulting in the formation of a significant number of blast bodies, which have absolutely all signs of malignancy.
Risk factors
The main risk factors for the syndrome include:
- Human being male.
- The presence of white skin.
- The patient is over sixty years old.
- Chemotherapy preceding the disease along with radiation.
- The effect of certain chemicals. An example is tobacco smoke along with pesticides, solvents.
- Exposure to the body of various heavy metals, such as mercury with lead.
Next, we find out how this disease can manifest itself and what are its main symptoms.
What are the main manifestations of the syndrome?
The likely manifestations of myelodysplastic syndrome with an excess of blasts may be, first of all, the appearance of weakness and shortness of breath. In the early stages of the disease, this syndrome is often not clinically manifested. Sometimes it happens that he is diagnosed by chance during a routine laboratory blood test. Similar symptoms may be due to other diseases. In the event that a person discovers at himself any of the following symptoms, he should immediately consult a doctor:
- The appearance of shortness of breath.
- The development of weakness along with a feeling of fatigue.
- The appearance of a pale skin color.
- The formation of bruises even as a result of minor bruises along with increased bleeding.
- Observation of the petechiae - flat, spot bruising under the skin the size of a pinhead.
- The appearance of fever or frequent infectious diseases.
Symptoms of myelodysplastic syndrome
The clinical manifestation of the syndrome directly depends on the degree of myelopoiesis involvement. In this regard, at the initial stage of the pathology, an asymptomatic period is observed in patients, which can last quite a long time. In situations where myelodysplastic syndrome occurs in patients due to the predominant symptom complex of anemic nature, patients experience increased weakness with pronounced pallor of visible skin, and they also have no appetite.
The presence of an increased predisposition to diseases of an infectious nature indicates the development of neutropenia. In addition, this group of patients has an increased risk of inflammatory complications. True, the thrombocytopenic component of the syndrome, which can manifest itself in the appearance of a hemorrhagic symptom complex in the form of increased bleeding, is the most difficult factor regarding the effect on patients' well-being. Frequent episodes of nosebleeds with the development of petechial elements of rashes on the skin can also be observed.
A qualitative diagnosis of myelodysplastic syndrome (refractory anemia) with an excess of blasts should include an assessment of the intensity of the clinical manifestations, as well as changes in the cellular composition of not only peripheral blood, but also bone marrow aspirate. In case of detection of signs such as refractory anemia, leukocytopenia or thrombocytopenia, as well as the combination of all these disorders in elderly patients, an assumption of the syndrome should be made.
Refractory anemia is characterized by a combination with anisocytosis, in addition, with macrocytosis, which can manifest itself in an increase in the average cell volume of the erythrocyte series. It is important to note that thrombocytopenia against the background of myelodysplastic syndrome most often does not reach a critical value, however, it can be accompanied by a change in the size of platelet cells. The latter will occur in the form of a decrease in their granularity. It is not necessary to observe a decrease in the white blood cell count. The most specific criterion is a change in the leukocyte plasma granularity with the presence of pseudo-Pelger cells. The presence of an increase in the concentration of monocytic blood cells will testify in favor of the formation of chronic leukemia of the myelomonocytic species.
Immunophenotyping along with a cytochemical analysis of bone marrow aspirate, which allows the determination of specific enzymes, serves as a highly accurate diagnostic technique, which has almost one hundred percent certainty. It should be noted that such enzymes are characteristic exclusively for blast cells.
Consider the classification of myelodysplastic syndrome.
Disease classification
In modern medicine, the following types of syndrome are distinguished:
- The development of refractory anemia. This form of the disease can persist for more than six months. Moreover, in the analysis of the patient’s blood, blasts will be absent or occur in a single order. In the bone marrow, as a rule, dysplasia of the erythroid germ is observed.
- The development of refractory anemia with sideroblasts. This form of pathology can also persist for more than six months. There will be no blasts in the patient’s blood test. Erythroid dysplasia is also observed in the bone marrow.
- The development of refractory cytopenia with multilinear dysplasia. Auer’s Taurus’s patient’s blood count is usually absent. As for the blast, they are also absent or occur in isolated cases. Pancytopenia with an increase in the number of monocytes can be detected. Within the bone marrow, dysplastic changes will be less than ten percent; Auer bodies are absent.
- The development of refractory anemia with a significant excess of blasts-1. Auer bodies are absent in the patient’s blood, and blasts comprise more than five percent. In parallel, cytopenia is observed with an increase in the number of monocytes. In this case, dysplasia of one or several cell lines at once will be observed in the bone marrow; Auer bodies are absent.
- The development of refractory anemia with an excess of blasts-2. In the patient’s blood, an increase in the total number of monocytes is observed, as well as cytopenia. Blasts make up nineteen percent; Auer bodies can be detected. In the bone marrow, as a rule, there is dysplasia of one or several cell lines at once.
- The formation of unclassified myelodysplastic syndrome. Cytopenia is observed in the patient’s blood, and blasts, in turn, are absent or occur singly. Auer bodies are absent. Within the bone marrow, dysplasia of one megakaryocytic germ can be observed.
- The development of myelodysplastic syndrome associated with an isolated deletion. In this case, anemia will be observed in the blood test, and blasts will make up more than five percent, thrombocytosis is not excluded.
Diagnosis
The diagnosis of the disease is based on laboratory data. As part of the study, the patient is assigned the following procedures:
- Peripheral blood test
- A bone marrow biopsy followed by a cytological examination.
- Submission of a cytochemical, cytogenetic test.
As part of the analysis of peripheral blood in people with pathology, as a rule, pancytopenia is detected, less often single-cell cytopenia can be detected. Among ninety percent of patients, doctors observe normocytic or macrocytic anemia. Sixty percent of patients show neutropenia with leukopenia. In addition, in most patients, doctors note the presence of thrombocytopenia. What else is the diagnosis of myelodysplastic syndrome?
In the study of bone marrow, the total number of cells is usually normal or increased. Already at an early stage, doctors can detect signs of dyserythropoiesis. The content of blasts directly depends on the type of syndrome, so their number can be normal or increased. In the future, doctors observe dysgranulocytopoiesis with dysmegakaryocytopoiesis. In some patients, signs of dysplasia within the bone marrow are very weak. As part of a cytogenetic study, chromosomal abnormality is detected in almost all patients. Now consider how the treatment of this syndrome is carried out.
What is the treatment for myelodysplastic syndrome?
Treatment
Until recently, the treatment of myelodysplastic syndrome was only symptomatic. Today, experts are developing new methods of therapy, however, effective treatment of this group of diseases is still one of the most complex problems of modern hematology. So far, the prognosis for myelodysplastic syndrome mainly depends on the characteristics of the course of the disease, the presence or absence of complications. Treatment is carried out by specialists in the field of oncology and hematology.
Making decisions about the choice of the main tactics of managing patients with this pathology directly depends on the severity of the laboratory manifestation. The absence of symptoms of hemorrhagic syndrome, anemia, a high risk of developing infectious complications is the basis for choosing a wait-and-see tactic for the patient. In a similar situation, exclusively dynamic observation of the laboratory criterion of myelopoiesis is indicated.
The use of a therapeutic technique to correct this syndrome can be justified only in cases of severe clinical manifestations, as well as with an increased risk of transformation into leukemia. As part of treatment for myelodysplastic syndrome, conservative and surgical techniques are usually used.
Accompanying substitution treatment, which involves the introduction of blood components in the form of red blood cells or platelet intravenously, is most widespread. It should be noted that prolonged treatment with the use of the hemocomponent will inevitably provoke a supersaturation of the patient’s body with iron, which in high concentrations only has a toxic effect on any organs and structures, which, of course, causes a violation of their functions. Given this feature, blood transfusion must be combined with the use of drugs that bind iron and contribute to its elimination. For example, the drug Desferal is used at 20 milligrams per kilogram of patient weight parenterally as part of chemotherapy for myelodysplastic syndrome.
Parenteral administration of substances such as erythropoietin and thrombopoietin is used for additional symptomatic therapy, which in no way affects the patient's overall life expectancy. This, in turn, serves as a priority indicator of the effectiveness of the treatment of this syndrome. The presence in patients of a phenomenon such as refractory anemia, as one of the signs of pathology, acts as a justification for the use of immunosuppressive treatment. For this, “Lenalipomide” is prescribed in a daily dose of 25 milligrams. Clinical recommendations for myelodysplastic syndrome do not end there.
The drug, whose effectiveness in preventing the development of leukemia against the background of the disease has been proven more than once, is "Azacitidine", its use is carried out according to a certain scheme. The first course of treatment is seven days, during which the patient is administered intravenously "Azacitidine" in a daily dose of 75 milligrams. During the subsequent cycle of therapy, the daily dose is 100 milligrams. Multiplicity of course treatment is a week every month. It should be noted that the effect of the use of "Azacitidine" can be very intense. In this regard, each use of the drug must be preceded by a clinical study of a blood test.
Assessment of hematological changes should be carried out after drug administration. A categorical contraindication for the use of "Azacitidine" is the presence in patients of severe organic pathologies of the liver and kidneys, since drugs of this pharmacological group are considered highly hepatotoxic. Given that the metabolic products in the framework of the breakdown of “Azacitidine” are eliminated through the excretory functions of the kidneys, conditions are formed for the toxic damage of these structures. In this regard, the use of the drug should be carried out strictly under the dynamic control of creatinine and urea values, these indicators are the main markers of renal failure.
Recommendations for myelodysplastic syndrome should be strictly followed.
Despite the positive benefits of the use of drug adjustment, the only reasonable method of therapy, which allows ninety-five percent of cases to achieve complete remission, is allogeneic transplantation of hematopoietic stem cell substrates, although the use of this method is practiced in the category of patients who are not older than fifty-five years. This factor, unfortunately, limits the use of this technique.
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- There is the so-called hematopoietic growth factor, which implies stimulation with proteins that promote the development of blood cells, their use makes it possible to reduce the need for replacement transfusion. True, many patients suffering from this syndrome do not respond to growth factors.
What is the disability group for myelodysplastic syndrome? This becomes known after a medical and social examination.
What is the prognosis for patients
Basically, the prognosis for a certain type of pathology directly depends on the pathogenetic variants of the course of the disease, as well as on the presence or absence of severe complications.
Recent scientific studies in the field of hematology relate to the development of prognosis assessment parameters for myelodysplastic syndrome. Hematologists use the international IPSS classification in their daily practice. According to the latter, there are three main categories of risk: low, intermediate and high.
The main parameter in assessing the prognosis for myelodysplastic syndrome is the percentage presence of blast cells in the bone marrow region. The profile of the chromosomal abnormality with the actual severity of cytopenia is also evaluated. The most favorable course of the disease is observed in patients who have zero points according to the IPSS classification. As for the average life expectancy in the presence of high risk according to this classification, it is no more than six months.
When a diagnosis of myelodysplastic syndrome is made, the question immediately arises of which doctor will help. In the event of the presence or suspicion of the formation of a pathology, it is extremely important to immediately consult a specialist such as a hematologist and a blood transfusiologist. The consultation will also be provided by an immunologist with an oncologist.