Hemoblastoses

Description:

Hemoblastoses - group of the tumors which developed from cells of the hemopoietic fabric. Hemoblastoses are subdivided into three groups:
Leukoses - malignant tumors of the hemopoietic fabric  with primary localization in marrow with the subsequent dissimination in peripheral blood, a spleen, lymph nodes and other fabrics.
Gematosarkoma - extra marrowy, originally local, tumors (it is preferential in lymph nodes) the presented growth of the blast cells forming solid tumors and with their possible generalization in the hemopoietic bodies including KM.
The lymphoma - the tumors consisting of end-stage lymphocytes and formed by growth of fabric identical to a lymph node, but is a little or the KM which are not striking at all.

Reasons of hemoblastoses:

The reasons of hemoblastoses are finally not found out, but a number of the factors influencing the frequency of their development is established.
1. IONIZING RADIATION.
Proofs of a role of ionizing radiation in development of leukoses is significant increase in 5-7 years of incidence of an acute miyeloblastny leukosis among residents of the Japanese cities of Hiroshima and Nagasaki which underwent atomic bombing and also increase in incidence of a myelosis among the patients receiving radiation therapy concerning malignant diseases of various localization. The ionizing radiation generally promotes developing of an acute leukosis and a myelosis (HML), is much more rare than lymphoma. The small doses of radiations applied in medicine with the diagnostic purpose does not influence to a nachastot of development of leukoses.
2. CHEMICAL COMPOUNDS AND MEDICINES.
Data on possible leykozogenny effect of some chemicals are saved up: benzene, flying organic solvents, number of medicines: chloramphenicol and especially cytostatics (leukeranum, Myelosanum, azothioprimas, Cyclophosphanum).
Chronic influence of benzene takes place at long smoking, and not only at active, but also at passive smokers. At the men smoking 20 packs of cigarettes a year risk to ache with an acute myeloid leukosis during life 3-4 times higher in comparison in non-smoking. Consider that 24% of cases of death of a myeloid leukosis are connected with smoking of cigarettes.
In development of leukoses the chemotherapeutic substances applied to treatment of malignant new growths can play a part. Melphalanum, Myelosanum, Azathioprinum, cyclophosphamide are considered as the most leykozogenny.
Chloramphenicol causes the KM aplasia from the outcome in an acute myeloid leukosis.
3. VIRUSES
The virus origin of leukoses and lymphoma at cattle, hens, mice, rats, cats, monkeys is confirmed.  Concerning a role of viruses in developing of leukoses at the person it is necessary to notice that only the role Epstein-Burra's herpes virus in development of a lymphoma of Berkitt and the HTLV retrovirus in development of the T-cellular lymphoid leukosis is proved. However the evidence that infection only with these viruses without influence of any accessory factors becomes the reason of development of a tumor is not obtained so far.

4. HEREDITY.
Some chromosomal anomalies, in particular Down syndrome (a trisomy on the 21st chromosome), Potau's syndrome (a trisomy on the 13th chromosome) contribute to development of myeloid leukoses. Incidence increases at the hereditary diseases which are followed by the increased fragility of chromosomes - Fankoni's anemias, an ataxy teleangiectasia.
5. EXCHANGE DISTURBANCES.
Some metabolites of tryptophane and tyrosine arising at disturbance of exchange of these amino acids are capable to cause chromosome mutations and to have immunosuppressive effect.

Pathogeny:

Now the clonal theory of a pathogeny of hemoblastoses according to which leukemic cells are posterity of one mutating hemopoietic cell predecessor is conventional. The mutation of a parent hemopoietic cell occurs under the influence of etiological factors and consists in damage of the genetic device of a cell therefore the hemopoietic cell gains ability to hyper proliferation and loses ability to be differentiated.
Leukoses pass two stages in the development: the first — formation of a benign monoclonal tumor; the second — formation of a malignant tumor with signs of polyclonal transformation. The first stage of formation of leukoses begins with a mutation of a parent hemopoietic cell, it gains ability to proliferate intensively and gives posterity of cells — a clone. At this stage the tumor consists of the cells which do not have atipizm signs, these cells still keep ability to differentiation, there is no innidiation in bodies and fabrics (high-quality tumoral growth). The posterity (clone) of the mutating cell is characterized by high predisposition to recurrent mutations that is connected with instability of a cellular genome. Therefore at the second stage of development of a leukemic clone owing to recurrent mutations of tumor cells there are new subclones which are characterized by extremely high ability to mutations, the tumor becomes polyclonal and gains lines malignant. Tumor cells still intensively proliferate, but at the same time lose ability to differentiation. Further the tumoral clone begins to develop under laws of a tumoral progression:
oppression of normal sprouts of a hemopoiesis in marrow;
replacement in the tumoral mass of the differentiated cells and tsitokhimichesk undifferentiated become blasts which lose ability to differentiation and quite often in general morphologically;
emergence of ability of leukemic cells to raise and breed out of bodies of a hemopoiesis;
leaving of leukemic cells from under control of cytostatic therapy.

As a result of a tumoral progression the clinical picture of a leukosis forms.

Classification:

Now leukoses classify, as a rule, on the basis of morphological and cytochemical features of substrate cells (the cells making tumor substrate).
First of all, leukoses are subdivided on acute and chronic. The division of leukoses on acute and chronic means not the course of a leukosis, and that morphological substrate which is the cornerstone of a disease. At acute leukoses - it is blast, undifferentiated cells, and at chronic leukoses are ripening and morphologically mature elements of blood.
Among a set of various classifications of acute leukoses the greatest recognition was gained by classification of the French-American-British group (FAB, 1976) on the basis of which allocate myeloid and lymphoblastoid forms of an acute leukosis. In turn in group of acute myeloid leukoses allocate 8 of their options, and in group of acute lymphoblastoid leukoses – 3 types.

FAB classification
OML divide into eight classes:
M0 - OML with the minimum maturing of cells - 3%
M1 - an acute miyeloblastny leukosis without maturing of cells - 16%
Sq.m - an acute miyeloblastny leukosis with maturing of cells - 32%
M3 - an acute promiyelotsitarny leukosis - 10%
M4 - an acute miyelomonotsitarny leukosis — 19%
M5 - an acute monocytic leukosis - 14%
M6 - an acute erythroleukosis — 6%
M7 - an acute megakarioblastny leukosis - less than 1%.

OLL is divided into three classes:
L1  - with small sizes of blasts;
L2 – with large the sizes of blasts;
L3 – with blast cells like cells at Berkitt's lymphoma.

Chronic leukoses are subdivided into leukoses of a myelogenetic and lymphogenous origin. Based on quantity of leukocytes in blood unit of volume, leukoses subdivide on: leukemic (the quantity of leukocytes are higher than 60 000); subleukemic (quantity of leukocytes from 6000-60000); aleukemic (the quantity of leukocytes are lower than norm).

Treatment of hemoblastoses:

Complex treatment of primary malignant tumors of bones allowed to increase percent of 5 years' survival considerably recently. In addition to amputation and an exarticulation of the affected extremity, carry out organ-preserving operations: an oncotomy with a bone resection. Widely apply polychemotherapy: antineoplastic antibiotics (адреомицин, фармарубицин, Bleomycinum), compounds of platinum (platizia), antimetabolites (methotrexate) before - and postoperative courses or as independent treatment, including at metastasises in a bone. Hormonal drugs are used at metastasises of a breast cancer (anti-estrogen), a prostate (anti-androgens). Radiation therapy of primary and metastatic tumors of bones is performed by the gamma radiation or a bremsstrahlung on the linear accelerator of electrons in a dose on the center of 40 Gr at the combined treatment or 60-70 Gr as independent treatment by a static method from 2-3 fields or method of mobile radiation. At metastasises of cancer of thyroid gland the radioiodine, cancer of milk and prostatic glands - osteotropny drug Metasteronum containing radioactive 89Sr is used.
Beam osteitises arise after radiation therapy malignant tumors, is more rare than other diseases. Sites of a necrosis of a bone tissue with their resorption and inertly current reparative processes are followed by changes of skin and indurative hypostasis of hypodermic cellulose. Pathological changes are possible. These changes need to be distinguished from a recurrence and metastasises of tumors.