Myelodysplastic syndrome
The content of the article:
- Causes
- Forms of the disease
- Disease stages
- Symptoms
-
Diagnostics
- Diagnostic criteria
- Differential diagnosis
-
Treatment
- Allogeneic hematopoietic stem cell transplant
- Other treatments
- Possible complications and consequences
- Myelodysplastic syndrome: prognosis
- Video
Myelodysplastic syndrome is a group of heterogeneous clonal blood diseases, united by the following signs: ineffective hematopoiesis, peripheral cytopenia, dysplasia in one or more hematopoietic germs with a high potential for transformation into acute myeloid leukemia.
Myelodysplastic syndrome develops due to abnormalities in the red bone marrow
Insufficient hematopoiesis is manifested by anemia, increased bleeding, and susceptibility to infections. Myelodysplastic syndrome (MDS) occurs in people of any age, including children, but people over 60 are more susceptible to it.
According to ICD-10, the code D46 is assigned to myelodysplastic syndromes.
Causes
Blood cells are synthesized and mature mainly in the bone marrow (this process is called myelopoiesis, and the tissue in which it occurs is called myeloid), then, having fulfilled its function and becoming old, are destroyed by the spleen, and new ones come in their place. In myelodysplastic syndrome, the bone marrow loses its ability to reproduce blood cells (all - erythrocytes, leukocytes, platelets, or only some) in the amount required by the body, immature cells (blasts) enter the blood, as a result of which it performs its functions worse. This is manifested by the symptoms characteristic of MDS. In about 30% of cases, the process of myelopoiesis becomes completely uncontrolled over time, the number of blast forms of blood cells increases, displacing normal, mature cells. When the number of blasts in the blood exceeds 20% (previously the threshold was 30%), the diagnosis of acute myeloid leukemia is made.
Depending on whether the cause of the bone marrow dysfunction is known or not, MDS can be classified as primary or idiopathic and secondary. Secondary occurs as a result of suppression of bone marrow function after chemotherapy or radiation exposure. Such an effect is usually part of anticancer therapy, that is, it is carried out for some type of cancer. In this case, MDS can be considered a complication.
Primary, or idiopathic, MDS occurs spontaneously, without any previous pathology, and for no known reason. Perhaps a genetic factor is a predisposing factor, since chromosomal changes are found in some types of syndrome.
Factors contributing to the development of MDS are:
- smoking;
- contact with carcinogenic chemicals (pesticides, herbicides, benzene);
- exposure to ionizing radiation;
- elderly age.
Forms of the disease
As mentioned above, MDS is divided into two types, primary and secondary.
Primary MDS is more common (about 80% of all cases), the majority of cases are elderly people (65-75 years old). Secondary MDS also mainly affects the elderly, for the reason that malignant tumors, and therefore their complications, are more common in them. Secondary MDS is less responsive to therapy and is associated with a worse prognosis.
In addition, MDS is divided into clinical types depending on the type of blast cells, their number and the presence of chromosomal changes, this classification was proposed by the World Health Organization (WHO). According to the WHO classification, the following forms of MDS are distinguished:
- refractory (i.e., resistant to classical therapy) anemia;
- refractory cytopenia with multilinear dysplasia;
- MDS with an isolated 5q deletion;
- MDS unclassified;
- refractory anemia with annular sideroblasts;
- Refractory cytopenia with multilinear dysplasia and annular sideroblasts;
- refractory anemia with excess blasts-1;
- refractory anemia with an excess of blasts-2.
Disease stages
In the course of MDS, three stages are distinguished, which, however, are not always clinically distinct from each other, the differences are determined by laboratory. This is the stage of anemia, the stage of transformation (intermediate between anemia and acute leukemia), and acute myeloid leukemia. Not all researchers agree with the definition of acute myeloid leukemia as a stage of myelodysplastic syndrome, since it refers to myeloproliferative disorders (i.e., those characterized by uncontrolled cell growth), thus not fully consistent with the characteristics of MDS.
Symptoms
The main symptoms of MDS are associated with manifestations of anemia. Patients complain of increased fatigue, dizziness, shortness of breath during exercise, which was previously easily tolerated. Anemia is associated with impaired production of red blood cells, resulting in a low level of hemoglobin in the blood.
In some cases, hemorrhagic syndrome develops, which is characterized by increased bleeding. The patient begins to notice that even minor superficial injuries cause bleeding that does not stop for a long time, bleeding of the gums, frequent and spontaneous nosebleeds, petechiae on the skin and mucous membranes, as well as multiple hematomas (bruises) or without connection with any trauma remembered by the patient may appear or after minor bruising or even pressure. Hemorrhagic syndrome is associated with thrombocytopoiesis disorders.
Patients with MDS are also found to be susceptible to infectious diseases. They often suffer from colds, skin bacterial and fungal infections. This condition is due to neutropenia (neutrophil deficiency).
In addition, signs of MDS can be:
- an unreasonable rise in temperature, often to high values (38 ° C and above);
- weight loss, decreased appetite;
- hepatomegaly;
- splenomegaly;
- pain syndrome.
Diagnostics
The main diagnostic method for MDS is laboratory. If myelodysplasia is suspected, the following are performed:
- Clinical blood test. In this case, anemia (macrocytic), reticulocytopenia, leukopenia, neutropenia are detected, with 5q syndrome - thrombocytosis. Pancytopenia is found in about half of the patients.
- Bone marrow biopsy. Cytosis is usually normal or increased, but in about 10% of patients it is reduced (hypoplastic variant of MDS), there are signs of impaired hematopoiesis of one or several hematopoietic sprouts, an increased content of blast forms, pathological sideroblasts (erythrocytes containing iron deposits) can be found. To identify abnormal phenotypes, a study of the immunophenotype of bone marrow cells is carried out, this allows differential diagnosis of MDS and non-clonal cytopenias, which is important for prognosis.
- Cytogenetic analysis. In 40–70% of patients, clonal cytogenetic abnormalities are found, especially often a deletion (monosomy) of chromosome 7 (7q) is observed, which is prognostically unfavorable.
- Determination of serum iron and feritin levels. The levels are raised.
- Determination of endogenous eryropoietin (at <500 IU / L, erythropoiesis-stimulating agents usually provide a good therapeutic response).
In 95% of cases, the diagnosis is made on the basis of cytological and histological analysis of the bone marrow.
Diagnosis of MDS is carried out by laboratory methods
Diagnostic criteria
To determine the MDS, special criteria have been developed, i.e., the conditions under which this diagnosis is made. The diagnostic criteria are as follows:
- 1-, 2-, or 3-germ peripheral (i.e., found in peripheral blood) cytopenia;
- dysplasia: signs of impaired hematopoiesis of at least 10% of cells of at least one hematopoietic lineage;
- characteristic cytogenetic changes (the presence of a pathological clone).
Cytopenia should be stable and observed for at least six months, however, if a specific karyotype is found, or it is accompanied by dysplasia of at least two hematopoietic sprouts, two months are enough.
For a diagnosis, other diseases accompanied by cellular dysplasia and cytopenia must be excluded.
If cytopenia is detected without other signs of MDS, idiopathic cytopenia is diagnosed, the value of which has not been established; when dysplasia without cytopenia is detected - idiopathic dysplasia, the meaning of which has not been established. This requires constant monitoring of the patient with repeated bone marrow examination after 6 months, since both of these diagnoses can progress to MDS and acute myeloid leukemia (or other myeloproliferative disease).
Differential diagnosis
MDS differentiates with the following conditions:
- anemia (primarily megaloblastic, sideroblastic and aplastic);
- acute myeloid leukemia;
- leukopenia with neutropenia;
- primary immune thrombocytopenia;
- clonal hematopoiesis with undefined potential;
- primary myelofibrosis;
- HIV;
- severe intoxication of various etiologies.
Treatment
In 1997, a special scale was developed, called the IPSS (International Scoring Prognostic System, International Prognostic System), dividing patients into risk groups. Treatment tactics are selected in accordance with a certain risk group, and, as the name implies, the prognosis is assessed.
Points are awarded based on three factors:
- the number of blast forms;
- the number of affected hematopoietic sprouts;
- cytogenetic category.
| Blast content in bone marrow,% | Less than 5 | 5-10 | - | 11-20 | 21-30 |
| Cytopenia | 0-1 | 2-3 | - | - | - |
| Karyotype | del (5q) del (20q) -Y, norm | (+8 chromosome, 2 abnormalities) | del (7q), more than 3 anomalies | - | - |
| Prognostic factor | 0.5 | 1.5 |
The sum of the points allows the patient to be assigned to a particular risk group:
| Points | Risk | Transition to acute myeloid leukemia in 23% of patients (years) | Median survival (years) | % of patients |
| Low | 9.4 | 5.7 | 31 | |
| 0.5-1 | Intermediate 1 | 3.3 | 3.5 | 39 |
| 1.5-2.0 | Intermediate 2 | 1.1 | 1,2 | 22 |
| ≥2.5 | Tall | 0.2 | 0,4 |
The method of treatment depends on the risk category, condition and age of the patient. When MDS is asymptomatic, low- or intermediate-risk patients may not be prescribed therapy; only follow-up is required.
Allogeneic hematopoietic stem cell transplant
This is the only radical method of treatment for MDS, that is, allowing to achieve recovery. It is indicated for patients assigned to the group with intermediate and high risk of 2, as well as patients with 1 intermediate risk with an increased percentage of blasts or unfavorable cytogenetic signs. The age of the patients is mainly up to 60 years (this criterion is being revised in connection with the improvement of the method; patients of an older age are considered as candidates for transplantation). Allogeneic transplantation requires the presence of an identical donor.
Stem cell transplant is a radical treatment for MDS
Other treatments
In addition to stem cell transplantation, the following can be used:
- Intensive induction therapy. It is indicated for patients under 70 years of age belonging to the high-risk group without adverse cytogenetic changes in good functional state without concomitant pathology, with the number of blasts ≥10%.
- Azatidine therapy. It is indicated for patients from groups with 2 intermediate and high risk, not suitable for allogeneic hematopoietic stem cell transplantation, as well as patients with symptoms from the group of low and 1 intermediate risk. Treatment is carried out until disease progresses or toxicity develops.
- Lenalidomide therapy is indicated for 5q– syndrome.
- Combined immunosuppressive therapy (antimonocyte globulin + Cyclosporin) is indicated for patients younger than 60 years of age with normal karyotype and blast count <5%, short period of dependence on red blood cell transfusion (less than 6 months) and the presence of HLA-DR15, or the presence of a paroxysmal nocturnal hemoglobinuria clone.
- Transfusion of erythrocyte mass, platelets.
- Hematopoietic growth factor therapy (recombinant erythropoietin, EPO).
- Taking immunosuppressive drugs (usually according to the antithymocyte globulin + Cyclosporin regimen).
- Low-dose chemotherapy (usually Decitabine or Cytarabine) - for patients in intermediate and high-risk groups with contraindications to high-dose chemotherapy.
Other treatment regimens are also used.
Possible complications and consequences
MDS is a severe blood disorder that transforms into acute myeloid leukemia in 30% of patients.
Myelodysplastic syndrome: prognosis
The prognosis depends on which risk group the patient belongs to. In low-risk patients, the median survival is 6 years after diagnosis. In high-risk patients, 6 months or less. Allogeneic hematopoietic stem cell transplantation contributes to the fact that a five-year survival rate can be achieved in 40-50% of patients. Correctly selected treatment contributes to the fact that the survival rate in high-risk patients increases up to a year.
Video
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Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
The information is generalized and provided for informational purposes only. At the first sign of illness, see your doctor. Self-medication is hazardous to health!
