Myelodysplastic syndrome

Myelodysplastic syndrome includes a group of diseases characterized by cytopenia in the peripheral blood, dysplasia of hematopoietic progenitors, bone marrow hypercellularity and a high risk of AML development.

Symptoms depend on which cell line is most affected, and may include weakness, fatigue, pallor (due to anemia), increased incidence of infection and fever (due to non-throttling), bleeding and a tendency to hemorrhages in the skin and mucous membranes (due to thrombocytopenia). The diagnosis is based on a general clinical blood test, a peripheral blood smear, bone marrow aspirate. Treatment with 5-azacitidine may be effective; When developing AML, standard protocols are used.

[1], [2], [3], [4], [5]

Causes of Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a group of diseases often called preleukemia, refractory anemia, Ph-negative chronic myelogenous leukemia, chronic myelomonocytic leukemia, or idiopathic myeloid metaplasia, resulting from a somatic mutation of hematopoietic progenitor cells. Etiology is often unknown, but the risk of developing the disease increases with exposure to benzene, radiation, chemotherapeutic drugs (especially with prolonged or intensive regimens of chemotherapy, using alkylating agents and epipodophyllotoxins).

Myelodysplastic syndrome is characterized by clonal proliferation of hematopoietic cells, including erythroid, myeloid and megakaryocytic forms. Bone marrow is normal cell or hypercellular with ineffective hematopoiesis, which can lead to anemia (most often), neutropenia and / or thrombocytopenia. The disturbance of the cell production is also accompanied by morphological changes in the bone marrow or blood. There is extramedullary hemopoiesis, leading to hepatomegaly and splenomegaly. Myelofibrosis in some cases is accidentally detected when the diagnosis is established, but can develop throughout the course of the disease. Myelodysplastic syndrome is classified according to the peculiarities of blood and bone marrow. The clone of the myelodysplastic syndrome is unstable and tends to transform into acute myeloblastic leukemia.

[6], [7], [8], [9]

Symptoms of Myelodysplastic Syndrome

Symptoms of the disease depend on the most affected cell line and may include pallor, weakness and fatigue (anemia); fever and infections (neutropenia); easily formed hemorrhages in the skin and mucous membranes, petechiae, nosebleeds, bleeding mucous (thrombocytopenia). The characteristic signs of the disease are splenomegaly and hepatomegaly. In the development of symptoms can also contribute co-morbid diseases; for example, anemia in myelodysplastic syndrome in elderly patients with cardiovascular diseases can enhance angina pectoris.

Diagnosis of myelodysplastic syndrome

Myelodysplastic syndrome is suspected in patients (especially the elderly) with refractory anemia, leukopenia or thrombocytopenia. It is necessary to exclude cytopenia in congenital diseases, deficiency of vitamins, side effects of drugs. The diagnosis is based on the study of peripheral blood and bone marrow with the identification of morphological anomalies in 10-20% of cells of individual cell lines.

Characteristic features of bone marrow in myelodysplastic syndrome

Classification	Criteria
Refractory anemia	Anemia with reticulocytopenia, normal or hypercellular bone marrow, erythroid hyperplasia, and erythropoiesis disorder; blasts ^ 5%
Refractory anemia with sideroblasts	The same signs as in refractory anemia, as well as ring sideroblasts> 15% of HSCA
Refractory anemia with excess blasts	The same signs as in refractory anemia, there is cytopenia> 2 cell lines with morphological abnormalities of blood cells; hypercellularity of the bone marrow with violation of erythropoiesis and granulopoiesis; blasts 5-20% of the ball
Chronic myelomonocytic leukemia	The same signs as in refractory anemia with excess blasts, absolute monocytosis; in the bone marrow the content of monocytic progenitors
Refractory anemia with excess blasts in transformation	Refractory anemia with excess blasts with one or more of the following: 5% blasts in the blood, 20-30% of blasts in the bone marrow, Aueur sticks in the granulocyte precursors

Anemia is a frequent manifestation and is accompanied by macrocytosis and anisocytosis. On an automatic cell analyzer, these changes are expressed in an increase in MCV (mean red blood cell volume) and RWD (the width of the distribution of the volume of erythrocytes). Usually, moderate thrombocytopenia is noted; in the smears of peripheral blood, platelets vary in size; some have a decrease in granularity. The level of white blood cells can be normal, increased or decreased. The cytoplasmic granularity of neutrophils is pathological, with anisocytosis and a different number of granules. Eosinophils may also have pathological granularity. Pseudopelgarian cells (hypo-segmentation of neutrophils) can be detected in the blood. Monocytosis is a characteristic feature of chronic myelomonocytic leukemia, in less differentiated subgroups immature myeloid cells can be found. Cytogenetic analysis reveals one or more clonal anomalies, more often with chromosome 5 or 7 lesions.

[10], [11], [12]

Treatment of myelodysplastic syndrome

Azacitidine alleviates symptoms, reduces the incidence of transformation into leukemia and the need for transfusions, and probably improves survival. In general, the therapy is supportive and includes transfusion of erythrocytic mass according to indications, platelets for hemorrhages and antibiotic therapy for infection. In some patients, injection of erythropoietin (maintenance of hemoglobin level), granulocyte colony-stimulating factor (severe granulocytopenia accompanied by symptoms) and thrombopoietin (with severe thrombocytopenia) is used as an important factor in supporting hematopoiesis, but this treatment does not affect the duration of life. An effective treatment is allogeneic transplantation of hematopoietic stem cells, and now in patients older than 50 years, the use of non-myeloablative regimens is being studied. Myelodysplastic syndrome response to acute myeloblastic leukemia therapy is similar to that of leukemia, age and karyotype play a significant role in the prognosis of the disease.

Prognosis for myelodysplastic syndrome

The prognosis depends to a large extent on the type of myelodysplastic syndrome and the presence of concomitant diseases. Patients with refractory anemia or refractory anemia with sideroblasts are less prone to progression to more aggressive forms and may die from other causes.