Miyelodisplastichesky syndrome

Description:

Miyelodisplastichesky syndrome (MDS) — the group of heterogeneous clonal diseases which is characterized by existence of a cytopenia in peripheral blood, a dysplasia in marrow and risk of transformation in an acute leukosis.

MDS is one of the most complex problems of hematology today. Only recently treatment of MDS was beyond the maintenance therapy which was carried out for the purpose of relief of symptoms.

MDS is pathology of the senior age group. 80% of cases of MDS are the share of faces 60 years are more senior. MDS at children's age meets extremely seldom. In the European countries among persons of 50-69 years 40 new cases of MDS on 1 million population are registered, and among persons there are 70 years and are more senior — 150 new cases on 1 million population. Incidence of MDS in the Russian Federation averages 3-4 cases on 100 thousand population a year and increases with age.

Symptoms of the Miyelodisplastichesky syndrome:

MDS distinguishes lack of a typical clinical picture. The symptomatology of MDS is made by dysmyelopoiesis effects, that is cytopenias: anemia, a neutropenia and thrombocytopenia (anemia of Hb is less than 110 g/l, neutrophils less than 1,800 on 1 microlitre of blood; the hematocrit is less than 36% of erythrocytes in a total amount of blood in an organism; thrombocytes less than 100,000 on 1 microlitre of blood).

Most often MDS demonstrates cytopenias, mainly anemia. At the same time it is necessary to differentiate MDS from iron or B12-of scarce anemia, posthemorrhagic anemia, anemia at chronic diseases and oncology or connected with a chronic renal failure, and also aplastic anemia, a paroxysmal night haemoglobinuria. 10% of patients have symptoms of an infection, and at a little smaller share of patients the disease is shown by bleedings.

In this regard diagnosis of MDS is based only on laboratory and tool methods from which are key the integrated clinical analysis of peripheral blood, some biochemical researches and the morphological analysis of aspirates and bioptat of marrow.

Differential diagnosis of MDS is also complicated owing to a set of the states having the general with MDS clinical laboratory manifestations.

Reasons of the Miyelodisplastichesky syndrome:

Primary (idioptichesky) type — 80-90% of cases, secondary  (owing to the previous chemotherapy, etc. factors) — 10-20%. The majority (80%) of cases of MDS are primary — idiopathic or de novo which (Latin — again appeared new).

Secondary MDS is the MDS type, much more adverse and resistant to treatment, possessing obviously more worst forecast in comparison with primary MDS. 10-20% of cases of MDS arise owing to the previous chemotherapy concerning other new growths. Alkylating agents (Cyclophosphanum), inhibitors, topoisomerases — antineoplastic agents of a plant origin (топотекан, иринотекан, etc.), anthracyclines (doxorubicine) and podophyllotoxins treat the drugs having the proved ability to damage a genome with the subsequent development of MDS (этопозид). The radiotheraphy and contact with toxic materials can also lead to MDS.

Risk factors, primary MDS:

    * Contact with toxins (gasoline, organic solvents, pesticides)
    * Radiation
    * Smoking
    * Inborn and hereditary diseases
    * Advanced age

Risk factors, secondary MDS:

The previous chemotherapy of an oncological disease or after TKM.
Forecast: 5-year survival at MDS does not exceed 60%. Transformation in an acute leukosis ~ 30% of cases.

Treatment of the Miyelodisplastichesky syndrome:

Not all patients with MDS need therapy. Patients without anemic, hemorrhagic syndrome, infectious complications can be observed and not receive treatments (tactics of "watch and wait").

The choice of therapeutic tactics in many respects will be determined by age of the patient, the somatic status, a risk degree by a scale of IPSS, WPSS, presence of the compatible donor.

It is possible to allocate the following directions of therapy of MDS:

    * Accompanying therapy includes transfusion of various haemo components (a packed red cells, a trombokontsentrat), therapy by erythropoetin, trombopoetiny. At the patients who are often receiving hemotransfusions the organism overload iron develops. Iron possesses toxic action on various fabrics and bodies, first of all heart, liver therefore such patients have to receive the drugs connecting iron — helator (desferal, эксиджад).

    * Immunosuppressive therapy is most effective at patients with hypocellular marrow, a normal karyotype and existence of HLA-DR15. Lenalidomid possessing immunomodulatory and antiangiogenic action showed the efficiency at a third of patients with refractory anemia (according to criteria of WHO) and low risk (on IPSS), and also at patients with 5q-a syndrome. Efficiency of treatment in this case is very high; 95% of patients reach cytogenetic remission.

    * Allogenic transplantation of haematopoietic stem cells from compatible donors is a choice method at patients with a miyelodisplastichesky syndrome.
To patients with MDS 65 years, with the good somatic status are younger, in the presence of the HLA compatible donor performing allogenic transplantation of marrow as transplantation is potentially radical method of treatment of MDS is shown.

    * Chemotherapy

        * Cytarabinum, low doses. Are widely used in Russia and in all Europe, for treatment of patients with MDS and OML which do not suit therapy by the TKM method or use of intensive chemotherapy.

Opinions of researchers concerning expediency of use of a low-intensive care disperse. Bowen D considers that there are no bases to recommend its routine use at MDS: 3 randomized large researches were executed (141 пац.), which showed that use of low doses of Cytarabinum does not increase life expectancy of patients with MDS. At the same time, in later research at patients with OML and MDS of high risk it was shown that life expectancy at patients at whom LDAC more, than in 1 cycle, was applied above, than at a maintenance therapy.

Thus, need for a low-intensive care with the proved efficiency and the best portability, than LDAC which will promote increase in survival of patients with MDS of high risk remains urgent.

        * The high-dose chemotherapy is used at patients with RAIB with hyper - and normokletochny bone, at transformation in OML. Five-year survival makes about 18%.

    * The hypomethylating drugs

The new promising therapeutic approaches which are widely discussed recently concerning which numerous clinical trials are conducted resulted from deep studying of biology of MDS. Among them it should be noted DNA methylation inhibitors (5 azacytidine, децитабин) and an immunomodulator — леналидомид. 5 azacytidine possess the double mechanism of action. It is built in not only molecule DNA, but also molecule RNA. In the course of DNA methylation the hypomethylating agents covalently communicate with DNK-metiltransferazoy that leads to reactivation of genes then the differentiation of hemopoietic progenitors and a normal hemopoiesis is recovered. Azacytidine, being built in RNA a molecule, thereby lowers its quantity in cells that results in cytostatic effect regardless of a cellular phase. On the basis of results of a research 3 of the phase AZA-001 — international, multicenter, controlled, in parallel groups in which patients of MDS of high risk / OML (WHO criteria) were compared to standard treatment (accompanying therapy, intensive chemotherapy, low doses of Cytarabinum) azacytidine was registered including in the Russian Federation, for treatment of these patients. It was shown that azacytidine by 2,5 times increases the general survival.