Myelodysplastic syndrome

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

Symptoms depend on which cell line is most affected and may include weakness, fatigue, pallor (due to anemia), increased frequency of infections and fever (due to neutropenia), and bleeding and tendency to bleed into the skin and mucous membranes (due to thrombocytopenia). Diagnosis is based on complete blood count, peripheral blood smear, and bone marrow aspirate. Treatment with 5-azacytidine may be effective; standard protocols are used if AML develops.

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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 that result from somatic mutation of hematopoietic progenitor cells. The etiology is often unknown, but the risk of developing the disease is increased by exposure to benzene, radiation, chemotherapeutic agents (especially prolonged or intense chemotherapy regimens, alkylating agents, and epipodophyllotoxins).

Myelodysplastic syndrome is characterized by clonal proliferation of hematopoietic cells, including erythroid, myeloid, and megakaryocytic forms. The bone marrow is normocellular or hypercellular with ineffective hematopoiesis, which may lead to anemia (most commonly), neutropenia, and/or thrombocytopenia. The impairment of cellular production is also accompanied by morphologic changes in the bone marrow or blood. Extramedullary hematopoiesis occurs, leading to hepatomegaly and splenomegaly. Myelofibrosis is sometimes discovered incidentally at diagnosis, or it may develop throughout the disease. Myelodysplastic syndrome is classified according to the characteristics of the blood and bone marrow. The myelodysplastic syndrome clone is unstable and has a tendency to transform into acute myeloid leukemia.

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Symptoms of myelodysplastic syndrome

Symptoms depend on the cell line most affected and may include pallor, weakness, and fatigue (anemia); fever and infection (neutropenia); and easy bleeding into the skin and mucous membranes, petechiae, nosebleeds, and bleeding from the mucous membranes (thrombocytopenia). Splenomegaly and hepatomegaly are characteristic features of the disease. Associated diseases may also contribute to the development of symptoms; for example, anemia in myelodysplastic syndrome in elderly patients with cardiovascular disease may exacerbate angina pain.

Diagnosis of myelodysplastic syndrome

Myelodysplastic syndrome is suspected in patients (especially elderly) with refractory anemia, leukopenia or thrombocytopenia. It is necessary to exclude cytopenias in congenital diseases, vitamin deficiency, and 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 impaired erythropoiesis; blasts ^5%
Refractory anemia with sideroblasts	Same signs as in refractory anemia, as well as ringed sideroblasts > 15% of the NSCC
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 impaired erythropoiesis and granulopoiesis; blasts 5-20% of the NSC
Chronic myelomonocytic leukemia	The same signs as in refractory anemia with excess blasts, absolute monocytosis; the content of monocytic precursors in the bone marrow is significantly increased
Refractory anemia with excess blasts in transformation	Refractory anemia with excess blasts with one or more of the following: 5% blasts in blood, 20-30% blasts in bone marrow, Auer rods in granulocyte precursors

Anemia is common and is accompanied by macrocytosis and anisocytosis. On an automated cell analyzer, these changes are expressed as an increase in the MCV (mean corpuscular volume) and RWD (red corpuscular distribution width). Moderate thrombocytopenia is usually observed; in peripheral blood smears, platelets vary in size; some have decreased granularity. The white blood cell count may be normal, elevated, or decreased. The cytoplasmic granularity of neutrophils is abnormal, with anisocytosis and variable granule numbers. Eosinophils may also have abnormal granularity. Pseudo-Pelger cells (neutrophil hyposegmentation) may be detected in the blood. Monocytosis is characteristic of chronic myelomonocytic leukemia; immature myeloid cells may be present in less differentiated subgroups. Cytogenetic analysis reveals one or more clonal abnormalities, most often involving chromosome 5 or 7.

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Treatment of myelodysplastic syndrome

Azacitidine relieves symptoms, reduces the incidence of transformation to leukemia and the need for transfusions, and probably improves survival. Therapy is mainly supportive and includes transfusions of red blood cells when indicated, platelets for hemorrhages, and antibiotics for infection. In some patients, injections of erythropoietin (to maintain hemoglobin levels), granulocyte colony-stimulating factor (severe symptomatic granulocytopenia), and, if available, thrombopoietin (for severe thrombocytopenia) are used as an important factor in maintaining hematopoiesis, but this treatment does not affect survival. Allogeneic hematopoietic stem cell transplantation is an effective treatment, and nonmyeloablative regimens are currently being studied in patients over 50 years of age. The response to therapy in myelodysplastic syndrome is similar to that in leukemia; age and karyotype play a significant role in the prognosis of the disease.

Prognosis for myelodysplastic syndrome

The prognosis depends largely on the type of myelodysplastic syndrome and the presence of comorbidities. Patients with refractory anemia or refractory anemia with sideroblasts are less likely to progress to more aggressive forms and may die from other causes.