Acute myeloid leukemia

Sharp leukemia — Heterogeneous group of clonal
Tumor diseases of the hematopoietic fabric characterized uncontrolled
proliferation, disruption of differentiation and accumulation in the bone marrow and
peripheral blood of immature hematopoietic cells.

• Anemic — reduced hemoglobin levels and
  the number of erythrocytes, which manifests itself
  weakness, decrease in working capacity, drowsiness, manifestations
  heart failure, heartbeat,
  weakness, shortness of breath, pallor of skin and mucous membranes, orthostatic
  hypotension, secondary angina and myocardial infarction, intelligent
  Chromota, clinic of respiratory failure in patients with chronic
  Broncho-pulmonary diseases (COPD).
• Granulocyteopenic — Infectious complications,
  due to a decrease in the number of granulocytes in the blood, which is manifested by high temperature and intoxication, as well as
  Local clinic (necrotic districts, ulcerative stomatitis, osteomyelitis
  Jaws after the extraction of the tooth) or generalized (sepsis, infectious endocarditis),
  more often bacterial, infection.
• Hemorrhagic
  — Hemorrhage in skin and mucous, nasal and gum bleeding,
  Gastrointestinal and renal bleeding, uterine bleeding, elevated
  Bloodfaction during operational interventions.
• Proliferative
  — Lymphadenopathy, Splenomegaly, Hepatomegaly, Hyperplastic Gingivitis,
  Pains in the bones, disorders of the function of the cranial brain nerves, headache, violations
  vision, general and focal neurological
  symptomatics, headache, priapism.
• Inxication
  — Weakness, decline in appetite, weight loss, sweating.

1. First
   Step in diagnostics is
   Clinical analysis of blood by taking blood sample from veins. In blood sample
   The number of blood cells (erythrocytes, leukocytes and their subtypes is determined, and
   Also platelets). When discovery in clinical analysis of blood more than 20%
   Blast cells can be diagnosed with acute leukemia.
2. At
   the absence of sufficient blood to diagnose the number of blasts, as well as
   The purpose of accurate verification of the diagnosis using additional methods
   Studies are shown to conduct an aspiration biopsy of the bone marrow.
   The study of the bone marrow includes a study of bone marrow aspirate
   (Analysis of my cellogram-cytological examination), in rare cases, spendpalobiopsy is carried out
   bone marrow for a histological study of the bone marrow.
3. IN
   quality of additional research methods to determine the variant of acute
   leukemia and prognostic markers are carried out:

• Cytoochemical
  Research (myeloperixidase, eserase, glycogen)
• Cytogenetic
  study — detection of chromosomal anomalies, such as absent or
  Additional chromosomes in bone marrow cells by standard analysis
  Metafaz or FISH method
  (Fluorescent
  In. hybridization
  situ — Method based on the ability
  chromosomal DNA (target) to contact under certain conditions with small
  DNA sequences (probes), complementary this chromosomal DNA. At
  Accession to the fluorescent substance probe produce DNA analysis by its
  location of cells in interphase cells). The results of cytogenetic
  Studies are worn both diagnostic importance and prognostic.

• Molecular biological
  research (genetic research is carried out to identify characteristic
  mutations that can affect the outcome of the disease — For example, FLT3-tyrosine kinase, CD117 gene, retired for the receptor synthesis
  Stem cell growth factor C- Kit, Cebra genes,
  Baalc, ERG, NPM1.
• Study
  On tumor cells of differential antigens (CD) by flow cytometry (immunophenotyping).

• Primary-active
  stage — time interval between first clinical manifestations
  Diseases, diagnosis and the first full remission
• Full
  Clinical hematological remission — The number of blast cells in myelogram
  Decreases less than 5%, there are no extra-visa leukemic foci
  lesions, while in peripheral blood should not be blast cells,
  Number of platelets 100×109 / l leukocytes 2.5 x
  109 / l, granulocytes 1.0 x
  109 / l, hemoglobin level of 100 g / l.
  Recently, the concept of cytogenetic and molecular biological
  remission.
• Stage
  minimum residual (residual) disease.
• Recurd
  Diseases (bone marrow, extraotic surge).
• Terminal
  stage.

1. To control the symptoms of the disease or cure of the IML in young patients use
   Intensive chemotherapy to destroy the clone of pathological
   cells and reach long remission. This treatment method has
   Significant side effects, such as hair loss, the appearance of stomatitis
   oral cavity, nausea, vomiting, appearance of liquid stool. In addition to these side
   phenomena, chemotherapy has adverse effects and healthy
   cells that require a long stay in hematological
   Departments. At this time, the patient is carried out over-blood cell and
   thrombocyte mass, antibacterial drugs are prescribed to combat
   infection. If induction chemotherapy provides adequate control over
   pathological cells (state of remission), then restoration of normal
   Blood cells should begin within a few weeks. However, even in cases
   Successful treatment disease can be returned — recur.
2. The only one
   known method of treatment capable of healing most patients with OML,
   is the transplantation of allogeneic (donor) hematopoietic stem
   cells. It should be borne in mind that this is a complex risk-related procedure
   early and late complications. The outcome of treatment depends on the degree of compatibility (HLA compatibility) of the donor and the patient
   (recipient), as well as on the availability of suitable donor cells (availability
   Compatible blood brothers and / or sisters, availability of donor bank). Thus
   The way there are strict testimony and contraindications for this type of treatment:
   It is suitable for those cases when patients are able to transfer
   Stem cell transplantation and have a suitable donor and answered chemotherapeutic treatment.
3. Study
   The mechanisms of development of MDS / secondary IML, undertaken in recent years showed,
   that for this pathology is characterized by hypermetilization of the promoter region
   some genes-oncosuppressors, which leads to «Silence» These genes I
   Proliferation of tumor cells and transformations in the IML. On the basis of these knowledge
   The so-called hypometaling agents that contribute were developed
   DNA hypomettylation, causing expression earlier «Disabled» Genov.

In May 2004, management
USA for food and drug control (Food and Drug Administranion, FDA) issued permission to use
Injection preparation Azacytidin (Vaidaza) for the treatment of all types of MDS. In the Russian Federation
The drug was approved for use in 2010, including for the treatment of both MDS and IML. The results of the study showed that
Azacytidin reliably prolongs life to patients with acute myeloid leukemia,
Scheduled stem cell transplantation / intensive
chemotherapy. The studies show that the survival rate of patients with an OML without modern treatment is 1.6
months, while Azacytidin increases lifespan with IML
11.1 months, possessing favorable
Safety profile. Besides,
the drug, with sufficient qualifications of medical personnel, may
Apply Ambulator.

According to the protocols adopted in Russia, the treatment of patients IML, which are not
Suitable for intensive
chemotherapy and secondary OML is carried out by low doses of cytarabine and / or with
using supporting therapy [one]. Such therapy
Improves the quality of life of patients, but does not increase their life
in comparison with the natural course of the disease. While use
Azacitidine in this category of patients can radically change the flow
Diseases (Table 1).

table
one. The average total survival in the patients of the IML, depending on therapy (indirect
Comparative data).

	Without treatment	Supporting therapy	Low doses of cytarabin	Azacytidin
Oml, including number Oml S The number of blasts in myelogram 20-30%	1,6	13,4	17.0	24.5

Median survival of patients with OML (20-30% of blasts),
receiving azacytidine, increases to 24.5 months. At the same time, the differences in the group
Azacytidine with groups of supporting therapy and low doses of cytarabin
statistically reliable (p = 0.045), regardless of age or karyotype, and
Optional months of life are 11.1 and 7.5 respectively (median
survival in the supporting therapy group equals 13.4 and in the low group
Doses of cytarabin — 17.0 months) (analysis of data research III phase AZA-001) [2]. After 2 years, 50.8% of patients in the group were alive
Azacitidine, which is 2 times more than in comparison groups (26.2%). For
Comparison — Patients with an OML who do not receive modern therapy (natural
The course of the disease) die within 7 weeks from the diagnosis.

For patients with an IML, not
Intensive chemotherapy / stem cell transplantation, treatment
azacytidine may be the only means of life prolonging and
helping to achieve long remission. In the AZA-001 study in the Azacitidine group to therapy response
(Criteria IWG
2000) reached 29% of patients (full and partial answer), 49% — achieved
Hematological improvement. Differences with comparison groups («Supportful
therapy», «Low doses of cytarabin») Statistically reliable (5 and 12%, 31 and 25%
respectively). Time to the progression of the disease was 14.1 months in
Group «Azacytididine» and 8.8 months in comparison groups (p = 0.047). Duration
The hematological response was 13.6 months on the azacytidine in comparison with
5.2 months on traditionally used therapy (p = 0.002).

In patients with MDS and IML who received
Therapy ascitidine was observed a higher probability of independence from
Transfusions of the erythrocyte mass: 45% of patients became independent from
Hemotransphus, while on traditional modes — Only 11% (P < 0.0001).

Thus, the treatment of ascitidine of patients Oml (20-30% of blasts)
accompanied not only by a higher life expectancy and total
Remissary frequency compared to supporting therapy and low doses of cytarabina,
but also higher hematological improvement and independence
Transfusions. Patients with MDS High Risk Azacytidine Therapy
accompanied by an increase in time before transformation into an OML (17.8 months VS 11.5 months, p<0.001).

Azacytidin is included in the International Protocols for Treatment
Patients with myelodsplastic syndrome and IML in patients over 60 years.

USA: in the National Oml Treatment Guide
Oncological network (National Cancer Comprehensive Network, NCCN, USA) (2010) Azacytidine is recommended for application
patients older than 60 years who are not candidates for highly visible
Chemotherapy. Recommendations are given with a high level of evidence.

TO
undesirable phenomena of 3-4 degrees developing against the background of the treatment of azacytidine,
treat hematologic (71.4%), including thrombocytopenia (85%), neutropenia
(91%) and anemia (5