Myelodysplastic syndrome is a group of hematological diseases in which cytopenia, dysplastic changes in the bone marrow and a high risk of acute leukemia are observed. There are no characteristic symptoms, signs of anemia, neutropenia and thrombocytopenia are detected. The diagnosis is made taking into account the data of laboratory tests: a complete analysis of peripheral blood, histological and cytological examination of biopsy and bone marrow aspirate, etc. Differential diagnosis can present significant difficulties. Treatment – transfusion of blood components, chemotherapy, immunosuppressive therapy, bone marrow transplantation.
Meaning
Myelodysplastic syndrome is a group of diseases and conditions with disorders of myeloid hematopoiesis and a high risk of acute leukemia. The probability of development increases with age, in 80% of cases this syndrome is diagnosed in people over 60 years old. Men suffer slightly more often than women. In children, myelodysplastic syndrome is practically not found. In recent decades, hematologists have noted an increase in morbidity among people of working age. It is assumed that the cause of the “rejuvenation” of the disease could be a significant deterioration of the environmental situation.
Until recently, the treatment of myelodysplastic syndrome was only symptomatic. Today, specialists are developing new therapies, but effective treatment of this group of diseases is still one of the most difficult 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. The treatment is carried out by specialists in the field of oncology and hematology.
Causes and classification
Taking into account the causes of development, there are two types of myelodysplastic syndrome: primary (idiopathic) and secondary. The idiopathic variant is detected in 80-90% of cases, and is diagnosed mainly in patients over 60 years of age. The causes of the occurrence cannot be determined. Among the risk factors for primary myelodysplastic syndrome are smoking, increased radiation levels when performing professional duties or living in an unfavorable environmental zone, frequent contact with gasoline, pesticides and organic solvents, some hereditary and congenital diseases (neurofibromatosis, Fanconi anemia, Down syndrome).
The secondary variant of myelodysplastic syndrome is observed in 10-20% of cases, it can occur at any age. The cause of the development is chemotherapy or radiotherapy for some kind of cancer. Drugs with proven ability to cause myelodysplastic syndrome include cyclophosphane, podophyllotoxins, anthracyclines (doxorubicin) and topoisomerase inhibitors (irinotecan, topotecan). The secondary variant is characterized by higher resistance to treatment, a higher risk of acute leukemia and a more unfavorable prognosis.
In the modern edition of the WHO classification , the following types of myelodysplastic syndrome are distinguished:
- Refractory anemia. It persists for more than six months. There are no blasts or single ones in the blood test. There is erythroid germ dysplasia in the bone marrow.
- Refractory anemia with annular sideroblasts. It persists for more than six months. There are no blasts in the blood test. There is erythroid germ dysplasia in the bone marrow.
- Refractory cytopenia with multilinear dysplasia. There are no Auer corpuscles in the blood test, there are no blasts or single ones, pancytopenia and an increase in the number of monocytes are detected. There are dysplastic changes in the bone marrow of less than 10% of cells in 1 myeloid cell line, blasts of less than 5%, no Auer bodies.
- Refractory anemia with an excess of blasts-1. There are no Auer corpuscles in the blood test, blasts of more than 5%, cytopenia and an increase in the number of monocytes. There is dysplasia of one or several cell lines in the bone marrow, blasts 5-9%, there are no Auer bodies.
- Refractory anemia with an excess of blasts-2. In the blood test, an increase in the number of monocytes, cytopenia, blasts of 5-19%, Auer corpuscles can be detected. In the bone marrow, dysplasia of one or more cell lines, blasts of 10-19%, Auer corpuscles are detected.
- Unclassifiable myelodysplastic syndrome. In the blood test, cytopenia, blasts are absent or isolated, Auer corpuscles are absent. There is dysplasia of one megakaryocytic or granulocytic germ in the bone marrow, blasts are more than 5%, there are no Auer corpuscles.
- Myelodysplastic syndrome associated with isolated deletion of 5q. There is anemia in the blood test, blasts are more than 5%, thrombocytosis is possible. In the bone marrow, more than 5% of blasts, Auer corpuscles are absent, an isolated deletion of 5q.
Myelodysplastic syndrome symptoms
Clinical symptoms are determined by the degree of myelopoiesis disorders. With mild disorders, a long-term asymptomatic or erased course is possible. Due to the low severity of clinical manifestations, some patients do not go to doctors, and myelodysplastic syndrome is detected during the next medical examination. With the predominance of anemia, weakness, shortness of breath, poor exercise tolerance, pallor of the skin, dizziness and fainting are observed.
With myelodysplastic syndrome with thrombocytopenia, increased bleeding occurs, gingival and nasal bleeding are noted, petechiae appear on the skin. Subcutaneous hemorrhages and menorrhagia are possible. Myelodysplastic syndrome with pronounced neutropenia and agranulocytosis is manifested by frequent colds, stomatitis, sinusitis or streptodermia. In severe cases, pneumonia or sepsis may develop. Infectious diseases are often caused by fungi, viruses or opportunistic microbes. Every fifth patient with myelodysplastic syndrome has an increase in lymph nodes, spleen and liver.
Diagnostics
The diagnosis is made taking into account laboratory data: peripheral blood analysis, bone marrow biopsy followed by cytological examination, cytochemical and cytogenetic tests. In the analysis of peripheral blood of patients with myelodysplastic syndrome, pancytopenia is usually detected, less often two- or single-stage cytopenia is detected. 90% of patients have normocytic or macrocytic anemia, 60% have neutropenia and leukopenia. Most patients with myelodysplastic syndrome have thrombocytopenia.
When examining the bone marrow, the number of cells is usually normal or increased. Already in the early stages, signs of dyserythropoiesis are detected. The number of blasts depends on the form of myelodysplastic syndrome, may be normal or enlarged. Subsequently, dysgranulocytopoiesis and dysmegacariocytopoiesis are observed. In some patients, the signs of bone marrow dysplasia are very weakly expressed. In the process of cytogenetic examination, chromosomal abnormalities are detected in three-quarters of patients. Differential diagnosis of myelodysplastic syndrome is carried out with B12-deficient anemia, folate-deficient anemia, aplastic anemia, acute myeloid leukemia and other acute leukemias.
Myelodysplastic syndrome treatment
Treatment tactics are determined by the severity of clinical symptoms and laboratory changes. In the absence of obvious signs of anemia, hemorrhagic syndrome and infectious complications, monitoring is carried out. With myelodysplastic syndrome with severe anemia, thrombocytopenia and neutropenia, as well as with a high risk of acute leukemia, concomitant therapy, chemotherapy and immunosuppressive therapy are prescribed. If necessary, bone marrow transplantation is performed.
Accompanying therapy is the most common method of treating myelodysplastic syndrome. Provides intravenous infusions of blood components. With prolonged use, it can provoke an increase in iron levels, entailing violations of the activity of vital organs, therefore transfusions of hemocomponents are performed while taking chelators (drugs that bind iron and promote its excretion).
Immunosuppressors are effective in the treatment of myelodysplastic syndrome with the absence of chromosomal abnormalities, the presence of the HLA-DR15 gene and hypocellular bone marrow. Chemotherapy is used when bone marrow transplantation is not possible. High doses of drugs are used for the transformation of myelodysplastic syndrome into acute leukemia, as well as for refractory anemia with an excess of blasts in normocellular and hypercellular bone marrow, low – when bone marrow transplantation is impossible. Along with the listed funds, hypomethylating agents (azacitidine) are prescribed to patients. The most reliable way to achieve a full-fledged long-term remission is bone marrow transplantation.
The prognosis depends on the type of myelodysplastic syndrome, the number of chromosomal abnormalities, the need for regular transfusions of blood components, the severity of clinical manifestations and the presence of complications. There are 5 risk groups. The average survival rate of patients with myelodysplastic syndrome, included in the lowest-risk group, is more than 11 years; with the highest – about 8 months. The probability of bone marrow rejection after transplantation is about 10%.