Acute myeloid leukosis

Description:

The acute myeloid leukosis (OML, acute not lymphoblastoid leukosis, acute myelogenetic leukosis) is a malignant tumor of a myeloid sprout of blood at which the changed white blood cells quickly breed. Collecting in marrow, they suppress growth of normal blood cells. OML the most widespread type of an acute leukosis at adults, incidence of it increases with age. Though the acute myeloid leukosis a disease rather rare — falls only 1,2% of fatal cases of malignant tumors in the USA to its share - its increase together with a population postareniye is expected.
Symptoms of an acute myeloid leukosis are caused by substitution of normal marrow leukemic cells that leads to decrease in quantity of red blood cells, thrombocytes, and normal leukocytes. The disease is shown by bystry fatigue, an asthma, frequent small injuries of the skin raised by bleeding, frequent infectious defeats. Still explicit cause of illness is unknown, however some risk factors of its emergence are revealed. As any acute disease, OML develops quickly, and without treatment is wrapped in a lethal outcome for several months, sometimes — weeks.
Several versions OML meet, treatment and the forecast for them is different. Survival level for five years fluctuates between 15-70%, and remission frequency — from 78 to 33% depending on disease subspecies. At the beginning of OML himiopreparatam treat to achieve remission; then the supporting himiolecheniye can be carried out, or change of the hemopoietic stem cells is carried out. The last researches OML at the genetic level allowed to develop tests by which it is possible to define quite precisely probability of survival of the patient and efficiency of this or that medicine for an individual case of OML.

Symptoms of the Acute myeloid leukosis:

The most part of symptoms of OML is caused by substitution of normal blood cells leukemic cells. The insufficient leucopoiesis causes a high susceptibility of the patient to infections — in spite of the fact that leukemic cells occur from predecessors of leukocytes, ability to resist to infekta at them is absent. Decrease in quantity of red blood cells (anemia) can cause fatigue, pallor, and an asthma. The lack of thrombocytes can result in easy damageability of skin and the raised bleeding.
Hematoma.
Precursory symptoms of OML often are not certain and are not specific, and can resemble symptoms of flu or other widespread diseases. Here some general symptoms of OML: fever, fatigue, loss of weight or a loss of appetite, short wind, anemia, the increased damageability of skin and mucous membranes and bleeding, petechias (flat, of the size of a pin head specks in skin on site hemorrhages), hematomas, an ostealgia and joints, and persistent or frequent infections.
At OML there can be an increase in a spleen but usually it slightly and asymptomatically. Increase in lymph nodes at OML happens infrequently, unlike an acute lymphoblastoid leukosis. Changes of skin in the form of a skin leukosis develop in 10% of cases. Occasionally at OML there is a Syndrome Suite, it is a paraneoplastic syndrome — a skin inflammation around the sites struck chloromine.
Some sick OML have a swelling of gums because of infiltration of fabrics leukemic cells. Occasionally the hloroma — dense leukemic weight outside marrow appears the first symptom of a leukosis. Sometimes the disease proceeds asymptomatically, and the leukosis comes to light the general blood test during routine inspection.

Reasons of the Acute myeloid leukosis:

A number of the factors promoting emergence of OML — other frustration of system of a blood formation, influence of harmful substances, ionizing radiation, and genetic influence was revealed.
Preleykoz.
"Preleykozny disturbances of a hemopoiesis, such as miyelodisplastichesky syndrome or myeloproliferative syndrome can lead to OML; the probability of a disease depends on a form of a miyelodisplastichesky or myeloproliferative syndrome.
Influence of chemicals.
Antineoplastic chemotherapeutic influence, especially alkylating substances, can increase probability of emergence of OML in the subsequent. The highest probability of a disease falls on 3 — 5 years after chemotherapy. Other chemotherapeutic drugs especially epipodofilotoksina and anthracyclines, also contact post-chemotherapeutic leukoses. leukoses of such look are often explained with specific changes in chromosomes of leukemic cells.
The influence of benzene and other aromatic organic solvents connected with professional activity as the possible reason of OML remains disputable. Benzene and its many derivatives show cancerogenic in vitro properties. Data of some observations confirm a possibility of influence of professional contacts with these substances on probability of development of OML, however other researches confirm that if there is such danger, then it is only an additional factor.
Ionizing radiation.
Impact of ionizing radiation increases probability заболеваня OML. At endured atomic bombing of Hiroshima and Nagasaki incidence of OML it is raised, just as at the radiologists who received high X-ray doses when measures of radiological protection were insufficient.
Genetic factors.
Possibly, there is hereditarily an increased probability of a disease of OML. There is a large number of messages on a set of family cases of OML when incidence exceeded average. The probability of emergence of OML at the immediate family of the patient is three times higher.
A number of inborn states can increase probability of OML. Most often it is a Down syndrome at which the probability of OML is increased by 10 — 18 times.

Treatment of the Acute myeloid leukosis:

Treatment of OML consists generally of chemotherapy, and is divided into two stages: induction and postremissionny treatment (or consolidation). The purpose of induction therapy is achievement of full remission due to reduction of quantity of leukemic cells to not found level; the purpose of the consolidating therapy consists in elimination residual, not found by modern methods the remains of a disease and treatment.
Induction.
For all OML subtypes except for M3 on classification of FAB, usually use induction chemotherapy Cytarabinum and anthracycline, (for example, daunorubitsiny or idarubitsiny. This way of induction chemotherapy is known under the name "7+3" — because Cytarabinum is entered intravenously kapelno by seven days in a row, and then three days in a row struyno enter видарабин in a daily dose. At such way of treatment remission occurs almost at 70% of sick OML. Also other ways of induction treatment, including monotherapy can be applied by high doses of Cytarabinum, or the drugs which are at a research stage. Owing to toxic impact of treatment, including suppression of a myeloid sprout and increase in probability of infectious complications by very old patient the induction chemotherapy is not offered, and less intensive palliative treatment of a himiopreparatama is appointed. OML M3 subspecies, acute promiyelotsitarny leukosis, also known under the name, almost in all cases are treated by drug PTRK (completely a trance - retinoic acid) in addition to induction therapy. At treatment of an acute promiyelotsitarny leukosis it is necessary to consider a possibility of development of a syndrome of the disseminated intravascular coagulation owing to receipt of contents of granules of promyelocytes in peripheral blood. Treatment of an acute promiyelotsitarny leukosis is exclusively effective, it is authentically proved by a set of documentary cases of treatment.
The purpose of an induction stage of treatment is achievement of full remission. Full remission does not mean that the disease is completely cured. More likely, the condition of full remission speaks about impossibility to find a disease in the existing ways of diagnosis. Full remission is reached at 50-70% of adult patients with for the first time the revealed OML, the difference depends on predictive factors about which it is told above. Duration of remission depends on predictive qualities of an initial leukosis. Generally all cases of remission without the additional, consolidating treatment download a recurrence.
Consolidation treatment.
Even after achievement of full remission it is probable, the few leukemic cells nevertheless survive. They so are not enough that it is still impossible to find them. In case of not performing posleremissionny, or consolidation treatment honor at all patients at the end — the ends there is a recurrence. Therefore to get rid of indefinable sick cells and to prevent a recurrence — that is to reach full treatment, additional therapy is necessary. The type of treatment after achievement of remission is defined individually depending on predictive factors and the general state of health of the patient. At predictively favorable subspecies of leukoses (for example, at inv(16), t (8; 21) and t (15; 17) usually appoint 3-5 additional courses of the intensive chemotherapy known as consolidation treatment. The patient with high risk of a recurrence (for example, in the presence of cytogenetic changes, the accompanying miyelodisplastichesky syndrome, or at OML connected with the previous treatment usually the tranplantation of allogenic stem cells of a hemopoietic row is recommended if the general state allows and there is a suitable donor. At OML with average probability of a recurrence (at normal cytogenetic indicators or with such cytogenetic changes which do not get into risk groups) the question of consolidation treatment is not so clear and is defined by a number of specific indicators — age of the patient, the general state of his health, system of values, and at last, presence of the donor of suitable stem cells.
That patient to whom change of stem cells after consolidation treatment is not shown carry out an immunotherapy by a combination of a histamine of a hydrochloride (tseplen) and pro-leukin. Such treatment allows to reduce probability of a recurrence by 14%, extending remission for 50%.
Thus, the high-intensity chemotherapy (VHT) and transplantation of marrow are recognized as standard therapy of OML.
However results of treatment, despite rather high answers at young people, remain unsatisfactory with persons 65 years (30-50%) connected with an early lethality (10%) and short duration of remission are more senior. More than a half with OML are patients of advanced age and/or with the significant accompanying pathology which, as a rule, cannot receive highly toxic schemes of chemotherapy therefore they apply low doses of Cytarabinum of Cytarabinum and the supporting treatment to their therapy: antibiotics and hemotransfusions.
Since 2010 in the USA it is recommended to apply to treatment of OML the hypomethylating agents (5 azacytidine, децитабин) at patients who are not suitable for transplantation of kostnogomozgovy cells / intensive chemotherapy. 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. 5 azacytidine possess the double mechanism of action. It is built in not only molecule DNA, but also molecule RNA. Thereby 5 azacytidine lower amount of RNA 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 - the international, multicenter, controlled research in parallel groups in which patients of MDS of high risk / OML (WHO criteria) were compared to standardly used therapy (accompanying therapy, intensive chemotherapy, low doses of Cytarabinum) azacytidine was registered including in the Russian Federation, for treatment of these groups of patients. It was shown that azacytidine by 2,5 times increases the general survival of patients with OML (criterion of WHO).