LEUKOSES (leukosis; grech, leukos white + - osis; synonym: leukemia, leukemia) — the tumor arising from the hemopoietic cells with obligatory damage of marrow and replacement of normal sprouts of a hemopoiesis.
Incidence of L. it is not identical in various age and ethnic groups. So, e.g., acute lymphoblastoid L. considerably the lymphoid leukosis — at advanced age meets at children's and youthful age, hron, more often. According to some authors, in the USSR acute L. make 3,1: 100 000, chronic 1,0 — 1,7: 100 000.
- 1 HISTORY
- 2 CLASSIFICATION
- 3 AETIOLOGY AND PATHOGENY
- 4 PATHOLOGICAL ANATOMY
- 5 CLINIC, DIAGNOSIS AND TREATMENT of LEUKOSES
- 6 MEDICAL EXAMINATION AND REHABILITATION
- 7 LEUKOSES AT CHILDREN
- 8 EXPERIMENTAL LEUKOSES
R. Virkhov in 1845 for the first time allocated leukemia as nozol, a form and noted its heterogeneity. Fridreykh (N. Friedreich, 1857) suggested to distinguish acute and hron, forms L., based on morphology of leukemic cells. P. Ehrlich in 1901 for the first time described qualitative changes in blood at leukoses, Shultts (Schultz, 1909) indicated the need uses cytochemical, methods for identification of a form of acute
L. V of 1867. K. Slavyansky, and also A. I. Shchastny and in 1904 Mr. of G. Banti assumed the tumoral nature of leukoses. Ziegler (To. Ziegler, 1906) acted with a hypothesis of innidiation of leukemic cells. In 1916 Mr. P. Morawitz introduced the idea of isolation of myeloid and lymphatic forms L. and basic impossibility of transition of one form in another.
Intravital diagnosis of L. improved after implementation of methods of a puncture of marrow (see. Sternal puncture ) and trepanobiopsiya (see). In understanding of a pathogeny of L. the big role was played by such methods of a research as cloning and cultivation of the hemopoietic cells of in vitro, the chromosomal analysis, etc.
Beginning of pathogenetic therapy of L. carry to 1948 when S. Farber for the first time achieved remission of acute L. at the child, having applied a methotrexate; further progress of treatment is connected with use of the schemes of discontinuous polychemotherapy for the first time offered by E. J. Freireich with soavt in 1964
Classification of L. the hl is based. obr. on morfol., cytochemical, and kariologich. features of leukemic cells. On these features all L. are divided into two basic groups — acute and chronic. L are carried to acute., at which the ground mass of tumor cells is presented by blasts, and to chronic such at which the ground mass of tumor cells is differentiated and the hl consists. obr. from mature forms of granulocytes or erythrocytes, lymphocytes, or plasmocytes. Thus, duration of a disease is not criterion for reference of L. to acute or hron, group of a disease.
To acute L. the following main forms L belong.: lymphoblastoid, miyeloblastny, promiyelotsitarny, monoblast, miyelomonoblastny, plazmoblastny, megakarioblastny, erythremic myelosis, nondifferentiable L. Besides, allocate a form of acute L., one of the main signs the cut is the small maintenance of blasts in marrow and blood at the first stages of a disease — so-called small, percentage (oligoblastny, smoldering) acute
L. K to group hron. L. belong: lymphoid leukosis, myeloleukemia, hron, erythremic myelosis, multiple myeloma (see), erythremias (see. Polycythemia ). Meet hron, a subleukemic myelosis less often (see. Osteomyelofibrosis ), hron, monocytic L. and Valdenstrem's macroglobulinemia (see. Valdenstrema disease ).
AETIOLOGY AND PATHOGENY
Reasons emergence of acute L. and hron, a myeloleukemia of the person can be disturbance of structure and structure of the chromosomal device both hereditarily caused, and acquired under the influence of some mutagen factors, one of which is ionizing radiation. Increase emergence of acute lymphoblastoid L is proved. lower 8 — 11 years after local radiation of a thymoma. The local fractioned x-ray radiation of a backbone concerning a spondylosis in a total dose of 2250 I am glad sharply increases incidence of acute L.
Analysis of frequency of acute L. and hron, a myeloleukemia among endured in 1945 atomic explosions in Hiroshima and Nagasaki confirmed etiol, a role ionizing radiation.
Miller (R. W. Miller, 1968) noted that use of radioactive phosphorus (32P) of a plant louse treatment of an erythremia caused development in the subsequent acute L. at 10% of all treated; it by 10 times exceeds frequency emergence it in control group. M. M. Degtireva (1974) found radiation induced aberation chromosomes in leukemic cells at an acute erythremic myelosis.
Reason development of L. also action of chemical mutagens is. A. Goguel et al. (1967) proved considerable increase of acute L. among the persons which were affected by benzene and also among patients, it is long receiving cytostatic immunodepressants (an imuran, leukeranum, sarcolysine, etc.). Facts of emergence of acute miyeloblastny L., an acute erythremic myelosis against the background of long chemotherapy hron, a lymphoid leukosis, Valdenstrem's macroglobulinemia and other limfoproliferativny diseases, and also emergence of acute L. against the background of chemotherapy of rhematoid polyarthritis, Wegener's granulomatosis [R. R. Love et al., 1975] confirm the assumption of a provocative role of chemical factors in L.
Pokazan's development contributing to L. role of hereditary defects myeloid and limf, fabrics. Taf (I. The m of Tough et al., 1961), Miller (R. W. Miller, 1968) noted noticeable increase of cases of acute miyeloblastny L., acute erythremic myelosis and hron. a myeloleukemia at patients with a Down syndrome (a trisomy on the 21st couple of chromosomes), Blum's syndrome (spontaneous ruptures of chromosomes). Frequency of emergence of acute L is increased. at persons with the hereditary pathology caused by not discrepancy of gonosomes (Klaynfelter's syndrome, Turner's syndrome, etc.). At Louis Bar syndromes, Viskotta — Aldrich, Bruton who are characterized by existence of hereditary defects in immune system cases of lymphoblastoid L are speeded up.; increase in frequency of L. it is noted at blood relatives of probands.
Cases of inheritance of a chronic lymphoid leukosis on dominant and recessive type are described (I. A. Kassirsky, 1970), low incidence of this form L is noted. in some ethnic groups and raised — in others. In all these cases not the L is inherited., and the increased variability of chromosomes contributing parent cells miyelo-and a lymphocytopoiesis to leukemic transformation.
The virus theory of an etiology of L moves forward. Virus causality of L. it is proved for L. birds, cattle and other animals. Virus nature of L. the person it is not established; it is known that hemotransfusion of sick L. to the healthy person does not cause developing of a disease.
By means of the chromosomal analysis it was succeeded to establish that at any L. there is a resettlement on an organism of tumoral leukemic cells descendants of one originally mutating cell. The proof of this process is uniformity of chromosomal markers in cells of all leukemic infiltrates, blasts of blood, marrow and cerebrospinal liquid, and also uniformity of markers at primary manifestation of acute L. and at its recurrence. Chromatid fragments, deletions of chromosomes, the dicentrics indicating mutagen influence are observed, in other cases the aneuploidy, polyploidy is noted. With the course of a disease there are new chromosomal changes indicating formation of a poliklonovost. The hypothesis of autokhtonny primary and multiple emergence of the leukemic centers was not confirmed.
The cytogenetic analysis allows to reveal a class of the cells which were L, initial for this form. (see. Hemopoiesis ). So, according to Blekstok, Garzón (Black-stock, Garson, 1974), the autoradiography with 59Fe with the subsequent karyotyping showed that at acute miyeloblastny L. the erythrocyte sprout bears a leukemic marker, a source of tumoral process is the cell predecessor of a myelopoiesis. Immunochemical data say that a source of blast cells at acute lymphoblastoid L. the cell predecessor of a lymphocytopoiesis is. The ground mass of cases hron, a lymphoid leukosis is presented by B-cellular option, but there is also a T-cellular lymphoid leukosis; also options with simultaneous representation In - and T lymphocytes in leukemic population are found that proves an origin of a disease from a cell predecessor of a lymphocytopoiesis.
Development of L. submits to patterns of a tumoral progression (see. Progression of a tumor ), described by L. Foulds in 1949.
By data A. I. Vorobyova (1968), instability of a genotype of malignant cells at L. causes emergence of new clones among which in the course of life activity of an organism, and also under influence to lay down. means the most autonomous clones «are selected». The progrediyentnost of a current of L is explained by this phenomenon., emergence of a refrakternost to cytostatic and hormonal therapy, emergence of new options of the leukemic cells capable to be implanted into not hemopoietic fabrics.
Various forms L. differ in an originality morfol, manifestations, however common features are inherent to them. All forms L. are characterized by system tumoral growths, coming from the hemopoietic cells. Leukemic growths (infiltrates, proliferata) in marrow are constantly observed, it is frequent in a spleen, limf, nodes, a liver, other bodies and fabrics. Leukemic infiltration quite often causes increase in the sizes and weight of bodies, formation of extensive knotty growths is possible. Leukemic process is naturally accompanied by signs of the general anemia, a hemorrhage, dystrophic and necrotic - ulcer changes, complications of the infectious nature. The listed specific and nonspecific changes, closely connected among themselves, define a pathoanatomical picture. Depending on a stage of a disease, a form L., the carried-out treatment the volume of leukemic growths and their prevalence in an organism, intensity of the accompanying changes can be expressed in various degree. At treatment often differ in cytostatic means of change from typical pathoanatomical displays of a disease.
Pathoanatomical diagnosis of L. and their private forms is based on the analysis of section data and an intravital research of the hemopoietic bodies, mainly marrow, by means of a trepanobiopsiya. More rare object of intravital studying are removed with the diagnostic purpose increased limf, nodes, knotty growths of various localization, biopsy material of a liver, a remote spleen.
Acute leukoses are characterized by growth of the low-differentiated leukemic (blast) cells.
Macroscopic manifestations of various forms of acute L. are similar among themselves in this connection their differentiation on section is not represented possible. During the opening of the dead signs of L. can be expressed in various degree depending on prevalence of process. At the developed picture of acute L. marrow of flat bones of dark red, rose-red color, juicy, fatty marrow in tubular bones is replaced with leukemic growths.
In some cases increase in a spleen comes to light, lymph nodes, a liver, a cut, however, it is expressed not so considerably, as at hron. L. The weight of a spleen in most cases increases by 2 — 3 times in comparison with age norm, the sizes and weight of a spleen are more rare remain normal even in the presence of leukemic infiltration, its significant increase is occasionally possible (to 700 — 1000 g). Dependences between degree splenomegalies (see) and duration of a disease (on a wedge, to data), and also a form of acute L. it is not established. Tissue of a spleen on a section of red color, with the erased drawing of a structure, sometimes there are heart attacks, the pulp gives plentiful scraping. Ruptures of the capsule even at massive leukemic infiltration arise seldom. Increase limf, nodes can be expressed in various degree and usually is system, nodes of one anatomic area are sometimes increased limf. In certain cases limf, nodes are not increased. Struck limf, nodes of a soft consistence, are not soldered among themselves, fabric of their rose-red color. The liver is, as a rule, increased slightly, on a section the small serovatobely strips corresponding to zones of leukemic infiltration are sometimes visible. Specific growths often come to light in digestive tract. In such cases swelling of gums, increase in almonds, group follicles (peyerovy plaques) of a small bowel and solitary follicles of a large intestine, sites of a diffusion thickening of a wall of a stomach and intestines is observed. The extensive centers of a necrosis of a mucous membrane are characteristic went. - kish. a path with an ulceration. Perforation of a wall of a gut, peritonitis is occasionally observed. At considerable prevalence of process nodular or diffusion whitish growths of leukemic fabric come to light in skin, an epicardium, a pleura, kidneys, heart, generative organs, and at children — in a thymus. Against the background of system leukemic infiltration at children approximately in 50% of cases and at adults in 10% of cases of acute L., uncured or steady against therapy, extensive knotty growths of various localization are observed (tsvetn. fig. 1 — 8).
At acute L. often defeat of c comes to light. N of page — a neuroleukosis — in the form of infiltration of a meninx and substance of a head and spinal cord, cranial nerves. Such defeat takes place at various forms of acute L., most often at acute lymphoblastoid L. at children. Leukemic infiltration of a meninx can be isolated or is combined with patol, changes of substance of a brain. Macroscopically the focal or diffusion thickening of an arachnoid membrane, extensive hemorrhages in it comes to light, the firm meninx is surprised less often. At leukemic infiltration of a brain the multiple dark red centers — from dot to several centimeters in the diameter are found, it is preferential in white matter. Sometimes there are extensive sites of a red softening of substance of a brain with break in cerebral cavities and under a firm meninx.
At acute L. the accompanying changes caused by insufficiency of a blood formation and leukemic infiltration are expressed: multiple hemorrhages, extensive necrotic - ulcer processes, complications inf. nature. In some cases these changes during the opening act into the forefront, and signs of L. are expressed poorly or are even absent (bodies are not increased in sizes, at adults in a diaphysis of tubular bones fatty marrow remains). Such picture can take place not only under the influence of treatment, but sometimes and at uncured patients. In similar cases diagnosis of acute L. on opening it is complicated and possible only after microscopy.
At microscopic examination differential diagnosis of forms of acute L. is based on cytochemical, features of the blast cells forming leukemic growths. The structure of blast cells, frequency of specific damage of various internals, character of an arrangement in them leukemic infiltrates differ at different forms very relatively in this connection cannot serve as the main criteria for establishment of a form of acute
L. V to practical work of pathologists at a research of the material of biopsies received from the hemopoietic bodies, and section material a form of acute L. usually is established taking into account data cytochemical, studying of intravital smears of peripheral blood and punctates of marrow. Identification of a form of acute L. at a research of fabric cuts it is carried out with the help gistokhy, the techniques including methods of definition of peroxidase, a glycogen on the basis CHIC reaction (see), activities of nonspecific esterase (with substrate alpha naftilatsetata and an incubation of control cuts in the environment with addition of sodium fluoride). For control and more detailed differentiation carry usually out also identification of lipids by Sudan in black B, activities of a hloratsetatesteraza, acid phosphatase. Gistokhim, the fabrics taken only during the first hours after death are subject to a research. Assessment of results should be carried out on thin sections (to 5 mk) at big increase in a microscope. Because in fabric cuts it is difficult to reveal positive CHIC reaction in a granular form and a degree of activity of acid phosphatase, especially at a small amount of positively reacting blasts, gistol, it is reasonable to combine a research with cytochemical, studying of cells in prints from the hemopoietic bodies. Treated patients have a definition of a form of acute L. it is complicated in connection with frequent change cytochemical, properties of blasts under the influence of cytostatic means. In such cases at a research of biopsy and section material a form of acute L. it is diagnosed on the basis of results cytochemical, studying of leukemic cells of peripheral blood and marrow prior to treatment. Some cytochemical indicators of blasts of the main forms of an acute leukosis are presented in the table (p. 459).
In marrow, according to a trepanobiopsiya, at the first stages of a disease of accumulation of blast cells are focal, in enough elements of active marrow are found. Acute circulatory disturbances, sites of a hypoplasia are quite often observed, necroses can be found. Progressing of a disease is characterized by increase in number and the amount of leukemic growths, their merge, and then diffusion infiltration of tissue of marrow. The quantity of normal hemopoietic cells considerably decreases. Often there is an infiltration of a periosteum, distribution of process to surrounding soft tissues is possible. Development of leukemic growths is followed by the expressed rassasyvaniye of a bone tissue, is preferential as a smooth resorption. Very seldom osteoclasts take part in this process. Owing to partial, and considerable expansion of marrowy cavities, thinning, and in some sites destruction of a cortical layer happens in places and a full rassasyvaniye of bone beams. At early children's age jumps are observed in a zone of an endostosis. At acute L. the focal new growth of an atypical bone tissue rich with osteoid, growth of fibrous fabric is seldom noted. Along with small focuses of a necrosis sometimes there are extensive infarktoobrazny coagulative necroses defined macroscopically in the form of ochroleucous dry sites; in a circle hemorrhages are observed, accumulation of macrophages (fig. 1) is possible. In the field of leukemic growths thinning and partial disintegration of reticular fibers quite often is found. Observations with a focal or diffusion myelofibrosis which comes to light at miyeloblastny L. V such cases at a puncture usually more often are described it is not possible to receive marrow and establishment of the diagnosis requires a research of material of a trepanobiopsiya.
Leukemic infiltration of tissue of spleen and limf, nodes is followed by reduction of the sizes (fig. 2) and numbers of follicles up to their total disappearance. In a spleen infiltration of trabeculas with a razvolokneniye of walls of trabecular vessels, with deformation and narrowing of their gleam is often observed, there are fields of hemorrhages. In limf, nodes there are in the beginning focal infiltrates which in process of progressing of a disease increase in sizes, and defeat becomes diffusion.
In digestive tract of growth are located in a mucous membrane and a submucosa, according to localization limf, accumulations in the beginning. Further they extend out of their limits in muscular and serous covers. In parenchymatous bodies leukemic infiltrates are localized in a stroma, can be gnezdny or diffusion. Development of dystrophic changes, adjournment of hemosiderin in a liver is quite often noted. Specific damage of lungs, very often observable at acute leukoses, is followed in many cases by inflammatory changes.
Also infarktoobrazny pneumonia, and also necroses of tissue of lung can meet melkoochagovy, drain bronchial pneumonia. At pneumonia fibrous and hemorrhagic exudate which sometimes contains a large number of blast cells is formed. In covers and substance of a brain at microscopy leykostaza, infiltration by leukemic cells of walls of vessels with their exit in perivascular spaces and formation in fabric of accumulations come to light, it is frequent with existence of erythrocytes. Sometimes hemorrhages without impurity of blasts meet. Heavy dystrophic changes of ganglionic cells, in some cases focuses of proliferation of a glia are characteristic. Leukemic infiltration on the course of cranial and spinal nerves, in sympathetic gangliya can take place. Patients with acute L., uncured or resistant to therapy, often die of an anemia and the heavy intoxication caused by progressing of a disease. High specific weight among causes of death is made by damage of a brain, pneumonia and sepsis. In certain cases death comes owing to deep dysfunctions of various bodies (heart, a liver, kidneys, adrenal glands) caused by massive leukemic defeat, extensive hemorrhages. Sometimes patients perish from massive profuse bleedings (nasal, intestinal, uterine), perforation of intestines, a rupture of a spleen, an exacerbation of tuberculosis against the background of leukemic process.
Patterns of development of leukemic process and the secondary changes accompanying it are similar at various forms of acute L. Odnako the patomorfologiya of some forms has quite expressed features.
The acute lymphoblastoid leukosis, especially at children, is most often characterized by massive defeat of all groups limf, nodes, a spleen, a thymus, is frequent with their significant increase. In a thymus leukemic infiltration is located in segments and causes destruction of an epithelial reticulum. In lungs of growth are localized preferential in walls and a circle of bronchial tubes, in a liver — in the field of portal fields. At widespread process of a proliferata come to light in went. - kish. path, c. N of page, kidneys, generative organs, etc. At children's and youthful age extensive knotty growths arise at this form more often and hl are localized. obr. in a thymus and limf, nodes of a front mediastinum. Quite often they extend to a pericardium, a pleura, tissue of lungs that leads to formation of a massive tumoral conglomerate. Growths in marrow and other bodies consist of blast cells of a lymphoid origin, the Crimea the high nucleocytoplasmic ratio is peculiar.
The acute miyeloblastny leukosis in the developed stage of a disease is characterized by the expressed leukemic infiltration of marrow and other bodies. In a liver leukemic growths are localized in sinusoidny capillaries and in the field of portal paths. The similar arrangement of infiltrates is available also at other more rare forms of acute L. (monoblast, miyelomonoblastny, nondifferentiable, promiyelotsitarny, etc.) therefore this sign cannot form the basis for differentiation of forms of acute L. V of lungs leukemic infiltration usually comes to light on the course of interalveolar partitions with an exit of blast cells in gleams of alveoluses (fig. 3), localization and in a circle of bronchial tubes, vessels, interlobular partitions is possible. At children at this form L. leukemic growths in a thymus are located in connective tissue layers, squeeze segments that is followed by increase in amount of argyrophil fibers. At adults development of multiple nodes in a periosteum of flat and tubular bones, kidneys, a liver, gonads, a fatty tissue (hypodermic, retrobulbar, cellulose of a big epiploon and a small pelvis), sometimes in skin, a conjunctiva, a firm meninx and marrow is typical. In some cases in the field of tumoral nodes and systemic lesions there is a green coloring of fabric (chloroleukosis). Similar changes can come to light also at L. at children.
At an acute monoblast leukosis along with damage of marrow leukemic process in a spleen, limf usually comes to light, nodes, it is frequent in a liver, easy and other bodies. Note development of nodular leukemic infiltrates in skin. Cases with massive knotty defeats are described.
At an acute promiyelotsitarny leukosis the hemorrhagic syndrome is sharply expressed, and hemorrhages in vitals are the main reason for death. Macroscopic signs of leukemic defeat often are absent. At microscopic examination leukemic infiltration in most cases does not go beyond the hemopoietic bodies. Development of knotty growths is not peculiar to this form. Infiltrates consist of the blast cells containing rough violet-brown granularity in cytoplasm.
The acute nondifferentiable leukosis meets seldom. Usually widespread leukemic infiltration with defeat of various bodies and fabrics comes to light. Leukemic growths are presented by blasts which do not give positive reactions to above-mentioned enzymes.
At an acute megakarioblastny leukosis in marrow a large number of atypical megacaryocytes and megakaryoblasts which are diffuzno disseminated in fabric comes to light, and in places form accumulations (fig. 4). The same cells in a significant amount contain in fabric and sine of a spleen, limf, nodes, gleams of small vessels of a liver, easy and other bodies.
The acute erythremic myelosis is characterized by system proliferation of nuclear cells of a red number of marrow, is frequent with dominance of eritrokariotsit among them. Increase in quantity of unripe cells of a myeloid row, preferential myeloblasts is at the same time noted.
At the last two forms macroscopically signs of L. are usually expressed poorly, at microscopy widespread leukemic infiltration comes to light.
At various forms acute and hron. L. regarding observations in a spleen and limf, nodes, and sometimes and in other bodies and fabrics multiple accumulations of eritrokariotsit, small on volume, are found. One authors connect emergence of these centers with a compensatory erythrogenesis, others — with development of the acquired autoimmune hemolitic anemia.
Some researchers [the Mat, Rappaport (G. Mathe, H. Rappaport), 1976] to acute L. carry a malignant histiocytosis [a malignant reticulosis (reticuloendotheliosis), a histiocytic marrowy reticulosis]. At this form system growths of cells, on morfol, to a structure corresponding to histiocytes microscopically are found. Often these cells have ability to phagocytosis, especially erythrocytes. Sometimes in zones of growths meet one - or multinucleate large cells hyperchromic kernels, plasmocytes. There are observations that leukemic infiltration in marrow, a spleen, limf, nodes, a liver is localized preferential on the course of sinusoidny capillaries. Perhaps significant generalized increase in the sizes limf, nodes, spleen, liver.
At a myelosis the typical pathoanatomical picture of a disease is observed in the developed and terminal stages. During the opening usually find the expressed signs of the general anemia, in certain cases sharp exhaustion. Gleams of vessels can be filled with clots of gray-pink or gray-green color. Regarding observations punctulate hemorrhages in skin, bruises in places of injections, pustulous damages of skin, sites of a necrosis are found. Marrow of flat and tubular bones very juicy, gray-pink or gray color (so-called putreform or pioidny marrow). There is a porosity of a bone tissue.
Increase in a spleen, liver is characteristic. In the majority of observations the weight of a spleen within 400 — 3000 g, occasionally reaches 5 — 6 kg; often there are fibrinous imposings on its capsule, the sclerosis of the capsule, commissure with surrounding fabrics is possible. Tissue of a spleen on a section of a homogeneous look, juicy, gray-pink color, the pulp gives not plentiful scraping, quite often there are ischemic and hemorrhagic heart attacks of various prescription, scleropigmental small knots. Separate observations of a rupture of the capsule in zones of fresh heart attacks or their purulent fusion are described. The weight of a liver usually does not exceed 3 kg, occasionally reaches 5 — 6 kg. On a section fabric with the greased drawing, yellowish color, it is frequent with multiple gray strips.
Limf, nodes are usually increased slightly, among themselves are not soldered, an elastic consistence, gray-pink color, sometimes to punctulate hemorrhages.
In certain cases increase in almonds, limf, follicles and peyerovy plaques with existence of focal necroses and ulcerations comes to light, however such changes meet considerably less than at acute L. Lungs are quite often increased in volume, grayish color, under a pleura and in the thickness of pulmonary fabric the melkopetlisty network of vessels is defined, sites of pneumonia often meet.
At microscopic examination in marrow unripe and mature cells of a granulotsitarny row (fig. 5) which ratio can vary prevail. According to trepanobiopsiya, in an initial stage of a disease in enough elements of an erythropoietic and megakariotsitarny row remain. In process of progressing of process their number decreases, lipoblasts disappear. Profound changes in a stroma in the form of a combination of processes of destruction to increase in quantity of fibroblasts, argyrophil and sometimes collagenic fibers are characteristic. Studying of marrow by method of a trepanobiopsiya in dynamics demonstrates that the myelofibrosis gradually accrues and is more expressed at patients with repeated remissions and exacerbations of a disease. In some cases in marrow the extensive centers of a necrosis take place; the expressed rassasyvaniye of a bone tissue is constantly observed. In a spleen and lymph nodes in the developed stage of a disease diffusion infiltration by myeloid elements, an atrophy of lymphatic fabric is found. Leukemic damage of a spleen often is followed by the fibrosis of a red pulp expressed in various degree, formation of fields of a sclerosis that along with infiltration and a plethora is the reason of increase in its weight. For hron, a myeloleukemia localization of leukemic infiltrates in a liver on the course of sinusoidny capillaries (fig. 6), in lungs — in the field of interalveolar partitions is characteristic. Infiltration of walls of small bronchial tubes, vessels, pleurae is quite often observed. Less than at acute L., the centers of leukemic infiltration arise in kidneys, a muscle of heart, in walls went. - kish. a path, in covers and substance of a brain, skin, endocrine glands and other bodies.
At blast crisis hron, a myeloleukemia leukemic infiltrates have widespread character, consist preferential of blast cells. Multiple hemorrhages are characteristic. Development of extensive knotty growths is possible. Causes of death of patients hron, a myeloleukemia are the sharp anemia, intoxication, accession inf. complications, hl. obr. pneumonia, sometimes associated diseases. At a blast aggravation death can be caused by hemorrhages in a brain, a muscle of heart, adrenal glands, extensive profuse bleedings, dysfunction of vitals owing to a prelum their knotty growths. In some cases death comes in connection with a rupture of a spleen, peritonitis.
Chronic lymphoid leukosis. During the opening of corpses of the patients who died in the developed stage of a chronic lymphoid leukosis, as a rule, generalized increase in the sizes of peripheral and visceral lymph nodes from 3 to 5 cm in the diameter and more is found. They are located in the form of packages, usually are not soldered among themselves, an elastic consistence. Fabric them on a section of gray, gray-pink color, it is frequent with multiple hemorrhages. The expressed increase in almonds, limf, follicles of intestines can be observed. Increase in a spleen and liver is typical, however it is expressed usually to a lesser extent, than at hron, a myeloleukemia. Weight of a spleen in most cases 600 — 800 g. Its capsule is thickened slightly, commissures with surrounding fabrics are possible. A pulp on a section of gray-pink, rose-red color, a homogeneous look, sometimes in it there are hemorrhages, ischemic heart attacks. The weight of a liver in the majority of observations does not exceed 3 kg, under the capsule and on a section the small centers of gray color are often visible.
Marrow of gray-pink color, is removed from the marrowy channel of tubular bones in the form of compact weight. In tissue of lungs macroscopically grayish dense sites, and also growths around bronchial tubes sometimes come to light. Quite often changes in skin in the form of knotty consolidations and various nonspecific defeats meet (shingles, a pyoderma, herpetiform dermatitis, etc.). Owing to massive increase limf, nodes regarding cases an edema of cavities, development of jaundice takes place. As well as at other forms, often there are signs of the general anemia, dystrophic changes of parenchymatous bodies.
Microscopically in marrow system growth of lymphocytes is found. At an aggravation of process along with end-stage lymphocytes prolymphocytes and lymphoblasts come to light. In marrow allocate three types of infiltration: diffusion, diffusion and focal, focal. At the first two types of infiltration expanded cavities of marrow contain a significant amount of the lymphocytes diffuzno disseminated in fabric or forming along with it compact accumulations (diffusion and focal type). Unlike other forms L., even at massive infiltration in marrow the small centers of a normal hemopoiesis remain, lipoblasts do not disappear completely. For hron, a lymphoid leukosis the sharp rassasyvaniye of a bone tissue and lack of signs of its new growth is characteristic. Data intravital gistol, researches of marrow show that the focal type of infiltration is observed in early stages of a disease. Unlike the lymphoid small knots revealed normal in marrow and also from the reactive nodulyarny lymphoid hyperplasia accompanying a number of diseases at hron, a lymphoid leukosis focal accumulations of lymphocytes are characterized by quite large sizes, are deprived of a clear boundary, tend to merge, contain prolymphocytes and lymphoblasts along with end-stage lymphocytes. Differentiation of these changes with metastasises in marrow of a lymphocytic lymphosarcoma in view of similarity morfol, pictures is based on features a wedge, displays of a disease. At the developed picture hron, a lymphoid leukosis in limf, nodes diffusion infiltration of fabric lymphocytes with full deleting of the drawing is found, edges can get via the capsule into a surrounding fatty tissue. In a spleen the follicles which are sharply increased in sizes without the centers of reproduction merging with each other are in certain cases visible, however there is a full deleting of the drawing owing to diffusion infiltration of fabric lymphocytes more often. Quite often fields of a sclerosis meet. In a liver extensive accumulations limf, cells are located with hl. obr. in the field of portal fields (fig. 7), but can meet also in sinusoidny capillaries. In invaded zones growth of argyrophil and collagenic fibers quite often takes place. Expansion of bilious capillaries and stagnation of bile, dystrophy, a partial necrobiosis and a necrosis of hepatocytes is often observed. In lungs of growth are localized in walls of bronchial tubes that leads to disturbance of their drainage function and promotes development of pneumonia. Sites of massive leukemic infiltration of tissue of lung can be observed. At microscopy gnezdny accumulations of lymphocytes quite often are found in a stroma of kidneys, covers and a muscle of heart, gonads, a fatty tissue etc. Very seldom specific infiltration of covers and substance of a brain meets. A frequent find is accumulation of lymphocytes in gleams of vessels of various bodies, especially at a considerable leukocytosis. In some cases at an aggravation hron, a lymphoid leukosis there are massive tumoral growths, outgoing hl. obr. from limf, nodes. Tumoral masses consists of large undifferentiated cells with ugly kernels, quite often in them sites of a necrosis, hemorrhage are found. Sharply expressed infiltriruyushchy growth is characteristic.
Among causes of death pneumonia has high specific weight. Also general anemia and abnormal liver function, hearts, easy and other bodies connected with massive specific defeat or their prelum and the main vessels increased limf, are nodes causes of death. Sometimes death comes from associated diseases — exacerbations of tuberculosis, a myocardial infarction, cancer, etc.
The chronic monocytic leukosis is characterized by growth of cells like the monocytes giving positive reaction to nonspecific esterase. On opening the changes inherent to widespread leukemic process are usually observed. Diffusion damage of marrow takes place, it is quite frequent — significant increase in a spleen, liver, involvement in process of all groups limf is possible, nodes, went. - kish. path. Quite often extensive tumoral growths, the localized hl come to light. obr. in a mediastinum and retroperitoneal space. The general exhaustion, an edema of cavities, an anasarca are frequent. Hemorrhages are usually expressed moderately.
A pathoanatomical picture at Valdenstrem's macroglobulinemia, a multiple myeloma, an erythremia, hron, a subleukemic myelosis (osteomyelofibrosis) — see. Valdenstrema disease , Multiple myeloma , Osteomyelofibrosis , Polycythemia .
Features of a pathomorphism of leukoses in connection with treatment
At modern methods of treatment a pathoanatomical picture L. both at children, and at adults often differs from typical in certain features. They are expressed by reduction of volume of leukemic infiltration and emergence hypo - and an aplasia in the hemopoietic bodies, strengthening of dystrophic and necrobiotic, and also fibrous changes, development various heavy inf. complications. Morfol, manifestations of a pathomorphism are most brightly presented at acute L., especially lymphoblastoid.
Suppression of leukemic process can be expressed in different degree both by reduction of the amount of growths, and their disappearance in various bodies. Depending on it at treated L. four main options morfol, changes can be observed: 1) focal reduction of leukemic growths in the hemopoietic bodies, hl. obr. in marrow; 2) considerable decrease in leukemic infiltration in hemopoietic and other bodies; 3) intensive suppression of leukemic process in marrow with preservation of extensive growths beyond its limits (extra marrowy localization); 4) the expressed widespread leukemic infiltration.
At all forms L. the most intensive suppression of leukemic infiltration is observed in marrow. During the opening marrow of flat bones ochagovo or throughout dryish, gray or gray-yellow color, in it there are sites of fatty tissue and dark red fields of hemorrhages. At microscopic examination the quantity of cells in marrow is reduced, the fields of devastation of various size consisting of an edematous stroma with presence of macrophages and single blast cells (fig. 8), a zone of hemorrhagic treatment are visible. Leukemic infiltrates are located ochagovo, contain many cells in a condition of a lysis, pycnosis, disintegration (fig. 9). The centers of a necrosis presented by the breaking-up leukemic cells and also sites of a total coagulative necrosis of fabric can meet simultaneous death of a stroma. Colossal cells with ugly hyperchromic kernels which emergence is connected with dystrophic changes of blast elements are sometimes visible. The same cells sometimes come to light in other bodies.
A dynamic research of material of trepanobiopsiya at patients with acute L. shows that reduction of leukemic infiltration with development of hypoplastic changes is naturally observed in marrow in a phase of formation of remission.
In a stage of full remission the recovery of active hemopoietic fabric expressed in various measure takes place, however nevertheless blast cells in the form of small accumulations or odinochno the located elements quite often are found. At acute, and also hron. L., proceeding with repeated remissions, often there is a noticeable increase in lipoblasts (fig. 10); in connection with prolonged use of corticosteroids processes of a resorption of bone substance accrue, reflection of what is sharp thinning, and in places final fracture of bone beams (fig. 10). These changes are most expressed at acute L. at children can be also followed by formation of limy metastasises.
Separate observations of widespread are described nephrocalcinosis (see). Noticeable decrease in the sizes of leukemic infiltrates is often noted in a spleen, limf, nodes, a liver (fig. 11). In these bodies, as well as in marrow, are found various sizes of the field of devastation, hemorrhagic treatment of fabric, group of leukemic cells with their disintegration; at a long current perhaps focal growth of argyrophil and collagenic fibers, partial recovery limf, fabrics in lymphoid bodies. At hron, it is long a treated myeloleukemia there is sharp fibrosis of a pulp of a spleen with reorganization of its structure (fig. 12), sites of a lipomatoz in limf, nodes. Under the influence of treatment in connection with reduction of volume of growths even more often at acute L. (even on condition of considerable life expectancy of the patient) limf, nodes, a spleen and a liver keep the normal sizes and weight or are increased slightly. At hron. L., though the sizes of bodies are increased, however is not so strong, as before use of cytostatic means.
Considerable suppression of leukemic process sometimes is followed by development widespread aplastic change in marrow. Such outcome is noted preferential at the massive combined treatment of acute L., and also in some cases hron. L. At the same time, along with almost total aplasia of marrow, big sites of devastation in other bodies, extensive multiple hemorrhages, heavy infectious and fungal complications are observed. In similar cases for the pathoanatomical diagnosis the particularly important becomes the retrospective analysis a wedge, pictures of a disease, detailed microscopic examination. The last quite often reveals small accumulation of leukemic cells, especially outside the hemopoietic bodies. Section cases of acute L are described., when at microscopy leukemic infiltration is not found.
At a part of treated patients with acute L., died during a recurrence of a disease, extra marrowy localization of process is found. Most often such growths come to light in c. N of page (fig. 13). Their localization in kidneys, easy, generative and other organs is possible.
In a small number of cases at the died patients acute and hron, forms L., the Crimea intensive treatment was carried out, the characteristic developed pathoanatomical picture of a disease comes to light. Such changes happen at a full refrakternost to treatment, is preferential at repeated aggravations of process.
At modern methods treatment in parenchymatous bodies, hl. obr. in a liver and heart, are more often noted deep dystrophic change up to formation of the centers of a necrosis. Cases of emergence of the centers of a necrosis in marrow are described. Development of the necrotic centers can be caused by disintegration of cells of leukemic infiltrates, a septicaemia, toxic impact on fabrics of medicamentous means. They can result from also sharp local disturbances of blood circulation, in connection with massive hemorrhages, leukemic infiltration. In certain cases dystrophic changes in a liver are caused by development inf. hepatitis.
The complication connected with treatment are ulcers in went. - kish. a path owing to use of corticosteroids. Cases of acute lymphoblastoid L are described. at children, the Crimea applied polychemotherapy and radiation of a brain and at which the fibrinoid necrosis of tissue of brain and a hyalinosis of walls of vessels, multiple small focuses of a necrosis of tissue of brain with demyelination are posthumously found.
It is specified also increase of cases of fibrosis in marrow, a liver, a spleen, especially at hron, a myeloleukemia (fig. 14). A part of researchers regard it as a result of replaceable growth of connecting fabric in response to disappearance of leukemic infiltrates under the influence of treatment. According to others, fibrous changes are connected with deep restructuring of bodies for the course of leukemic process and lengthening of terms of life of patients. At hron, a lymphoid leukosis even intensive treatment is not followed by development of a myelofibrosis though can take place periportal fibrosis in a liver and a sclerosis of a pulp of a spleen.
As a rule, the expressed atrophic processes in closed glands which are combined sometimes with a focal compensatory hyperplasia of cells are noted. At high doses of corticosteroids the macroscopic signs characteristic of Cushing's syndrome are possible (see. Cushing syndrome ). Owing to disturbance of purine metabolism under the influence of hormonal and cytostatic drugs loss of crystals uric to - you in kidneys with obstruction of a gleam of tubules is possible.
The thanatogenesis of leukoses in connection with use of modern methods of treatment significantly changed. Among causes of death of patients with acute L. considerably the specific weight of bacterial and fungal infections increased (70 — 75%, according to different authors). At the same time sepsis is characterized by existence in various bodies of the areactive centers of a necrosis with accumulations of microorganisms. Extensive fungal infections of mucous membranes, internals with a necrosis and disintegration of fabric are described. Pneumonia is quite often proximate cause of a lethal outcome. A part of patients perishes from hemorrhages in vitals, dystrophy of a liver, uraemia. In certain cases death comes from progressing of L. at a picture of generalized or extramedullary leukemic infiltration.
At hron, a myeloleukemia patients began to perish more often during blast crisis, the important place in a thanatogenesis is still taken by pneumonia, deep dystrophy of a liver, myocardium. Thanatogenesis hron, lymphoid leukosis, hron, monocytic L. did not undergo essential changes.
CLINIC, DIAGNOSIS AND TREATMENT of LEUKOSES
Table. Some cytochemical indicators of blasts of the main forms of an acute leukosis
During acute L. allocate the first acute period, remission and a recurrence. For all forms of acute L. the increasing causeless weakness, an indisposition, sometimes the short wind, dizziness caused by anemia is characteristic.
Increase in a spleen, liver and limf, nodes meets at all forms of acute L., but develops at lymphoblastoid L. Boleznennost of bones at effleurage more often, depending on infiltration of fabrics leukemic cells, confirms increase of process. The hemorrhagic syndrome caused first of all by thrombocytopenia is frequent (bleeding of mucous membranes, petekhialny rash on skin).
At the maintenance of leukocytes of blood lower than 1000 in 1 mkl, and also in the presence of the expressed leukemic infiltration often there are ulcer and necrotic damages of mucous membranes of an oral cavity (stomatitis), drinks (quinsy), a gullet, intestines (the so-called ulcer and necrotic enteropathy, edges can lead to perforation of intestines). The paraproctitis, septicaemia and other complications can develop.
In lungs, a myocardium and other fabrics and bodies leukemic blast infiltrates can appear. Usually these symptoms are observed against the background of «unmotivated» fever.
Remission of acute L. call a state, at Krom less than 5% of blasts (in blood they are absent) are found in the patient in marrow; less than 30% of lymphoid cells; in blood more than 100 000 thrombocytes and more than 3000 leukocytes in 1 mkl at a tendency to increase in their quantity; there are no extra marrowy leukemic proliferata. For lymphoblastoid L. at children obligatory criterion of completeness of remission is the normal composition of cerebrospinal liquid. Recovery from acute L. it is considered to be a condition of full remission for not less than 5 years.
The acute miyeloblastny and acute miyelomonoblastny leukosis most often occurs at adults. At the beginning of diseases a liver and a spleen of usually normal sizes, limf, nodes are not increased. The extramedullary leukemic centers are expressed poorly, emergence them (increase in a spleen, liver, infiltration of testicles, skin, etc.) means approach of a late stage of a tumoral progression. Frequency of full remissions at miyeloblastny L., according to L. G. Kovalyova, varies from 30 to 50%. These forms of acute L. in the beginning are quite often characterized by a deep cytopenia, thrombocytopenia, ROE at the same time can be normal or slightly accelerated.
Kernels of blast cells have gentle and structural chromatinic network, several small is frequent nukleol. Cytoplasm of blast cells contains auerofilny granularity or Auer's little bodies, gives positive reaction to myeloperoxidase, lipids, a hloratsetatesteraza, is diffuzno painted at CHIC reaction. Activity of nonspecific esterase low. Emergence of greenish coloring on a section of leukemic infiltrates — chlorine is connected with myeloperoxidase. With disease blast cells can gain new lines: expansion and deformation of cytoplasm, disappearance of granularity that emergence of new tumoral clones usually accompanies.
At a miyelomonoblastny form of an acute leukosis in blasts of a tsitokhimicheska not only Peroxidase, but also alpha naftilesteraza, characteristic of elements of a monocytic row comes to light, it is suppressed with sodium fluoride.
The acute lymphoblastoid leukosis, as a rule, from the very beginning proceeds with a lymphadenopathy, increase limf, nodes, a spleen and ossalgiya. In blood only moderate normokhromny anemia, acceleration of ROE can be noted in the beginning. Blast cells with a roundish kernel with gentle network of chromatin and one-two nukleola, bezzernisty narrow cytoplasm. Their characteristic feature is positive granular CHIC reaction, lack of peroksidazny and sudanophil inclusions in cytoplasm. Reaction to nonspecific esterase negative or slabopolozhitelny. High activity of acid phosphatase is noted at rare T-cellular option.
Acute a promyelocyte r N y y the leukosis is quite rare and is characterized by speed of a current. The expressed bleeding, hypofibrinogenemia are inherent in it. Peripheral lymph nodes, a liver and a spleen are usually not increased. In a gemogramma anemia, the expressed thrombocytopenia is noted; in marrow high percent of atipichesky blasts. Blast cells are various in size and a form, with the bluish cytoplasm which is densely filled with the large violet-brown granularity which is located and on kernels Auer's little bodies are frequent. Granularity contains the acid sulphated mucopolysaccharides. Kernels of these leukemic cells roundish or fabiform, with gentle or rough structure of chromatin, one-three nukleola, occupy a smaller part of a cell. In cytoplasm of cells a large number of lysosomes. These cells have only the remote looking alike promyelocytes and concern to predecessors of granulocytes. Cells give positive reaction to peroxidase, lipids, a hloratsetatesteraza, nonspecific esterase, diffusion coloring of cytoplasm at CHIC reaction. Detection in cells of the acid sulphated mucopolysaccharides is a specific cytochemical character.
The acute monoblast leukosis is rather rare. The typical beginning of this form differs from miyeloblastny a little. The hyperplasia of a mucous membrane of gums because of proliferat in them is often noted. In blood the high percent of granulocytes with rejuvenation is found. Blast cells have a fabiform kernel with several nukleola and grayish-bluish cytoplasm, sometimes with scanty azurophilic granularity. Tsitokhimicheski comes to light the positive reaction to an alpha naftilesterazu suppressed by sodium fluoride; reaction to peroxidase, lipids, CHIC reaction are expressed poorly or are absent. Activity of acid phosphatase moderate or high. In blood serum and urine of these patients a high level of a lysozyme. This form of acute L. will badly respond to treatment, remission is reached seldom.
The acute plazmoblastny leukosis is characterized by emergence in marrow and blood of plasmablasts and plasmocytes with lines of a cellular atipizm, and also undifferentiated blasts. Cytochemical methods do not reveal peroxidase. The extramedullary leukemic centers — the leukemids of skin increased limf, nodes, a liver, a spleen are quite often expressed. Feature of this form of acute L. — existence in blood of a paraprotein.
The acute megakarioblastny leukosis is very rare. Presence at marrow and blood of megakaryoblasts — cells with a blast, but hyperchromic kernel, narrow cytoplasm with threadlike outgrowths, and also undifferentiated blasts is characteristic of it. Quite often in blood and marrow ugly Megacaryocytes and splinters of their kernels meet. The thrombocytosis is characteristic (more than 1 000 000 in 1 mkl). To differentiate this form with hron, a myeloleukemia at blast crisis lack of a Ph-chromosome allows.
The acute erythremic myelosis (Di Guglielmo's syndrome) meets rather seldom. Peripheral limf, nodes are usually not increased, increase in a liver and spleen is in rare instances observed. A source of blasts — a cell predecessor of a myelopoiesis. Frequent transformation of an acute erythremic myelosis in acute miyeloblastny is explained by it, is more rare in miyelomonoblastny L. Zabolevaniye is characterized by a hyperplasia of cells of a red row without signs of sharp hemolysis. The progressing normo-or Hyperchromic anemia without reticulocytosis, increase in blood of B12 vitamin, the accruing leykotsitopeniye and thrombocytopenia is observed. In marrow — increase in maintenance of cells of a red row with presence of two - and three-nuclear erythroblasts with the overwound kernels and atypical undifferentiated blast cells, myeloblasts.
Unlike other forms of acute L., the differentiation of tumor cells of a red row occurs quite often to a stage of an oxyphilic normocyte or to an erythrocyte.
At diagnosis of this form of acute L. it is necessary to exclude first of all hemolysis, in particular autoimmune, and also pernicious anemia. Use of a trepanobiopsiya in difficult cases quite often allows to find proliferata of the undifferentiated cells not characteristic of not tumoral diseases. Sometimes only dynamic observation finds increase of level of blasts in marrow, and the diagnosis of an erythremic myelosis becomes undoubted. In leukemic cells at an acute erythremic myelosis the hypodiploidy and rough structural changes of chromosomes quite often come to light.
The acute low-percentage leukosis described by Reyngold (Reingold, 1963), Yu. I. Loriye et al. (1976), is characterized small (no more than 20%) by the maintenance of blast cells in marrow during a long term of a disease, and sometimes their quantity in peripheral blood exceeds that in punctate of marrow. On cytochemical, to signs blasts often belong to myeloblasts. Their distinctive feature is small sensitivity to different types of the existing therapy acute L. Obychno takes place early developing of anemia, tendency to a leukopenia and thrombocytopenia. Almost like the rule, peripheral limf, nodes and a liver are not increased, increase in a spleen is only in some cases noted. Disease quite often long — to y 1/2 — 2 years (is more rare more).
Diagnosis acute L. it is put on the basis of data cytologic research (see) blood and marrow, the blast forms finding high percent.
In blood at acute L. at early stages of a disease or there are blast cells (a leukemic stage), or they can be absent (an aleukemic stage). Both in the first, and in the second cases reduction of quantity of mature normal cells, usually two or all rows is noted hemopoiesis (see).
In marrow the maintenance of blasts at all acute L is noted high (tens of percent)., except for acute low-percentage L., at Krom within many months in blood and marrow the quantity of blast cells can be less than 15 — 20%; at the same time in marrow, as a rule, the percent of blasts is less, than in blood.
Establishment of a form of acute L. in each case carry out by means of cytochemical, methods. Kariologichesky, immunochemical, and other methods of a research have additional diagnostic and predictive value. Apply to assessment of completeness of remission tsitol, and gistol, studying of marrow of various parts of a skeleton. At acute lymphoblastoid L. children the lumbar puncture for an exception of neuroleukaemia is obligatory. Perspective for a prediction of probability of remission (or a recurrence) methods of cultivation of the hemopoietic cells in an agar are represented.
Differential diagnosis acute L. carry out with inf. a mononucleosis (see. Mononucleosis infectious ). Signs of acute L., the complications connected with a neutropenia intoxication develop gradually whereas for inf. a mononucleosis the acute beginning with high temperature, intoxication, morbidity increased limf, nodes is characteristic, as a rule.
Microscopic examination of the thin painted smears of peripheral blood helps to make the correct diagnosis. Atypical elements at inf. a mononucleosis never have structures of a classical blast cell: in blasttransformirovanny lymphocytes, characteristic of it, there is no tonkosetchaty kernel, structural from nukleola. In some cases acute monoblast L. in blood there can be many mature, though ugly monocytes that sometimes suggests an idea about inf. mononucleosis. At the same time in blood at acute L. always there is a certain percent of blasts that does not allow to refer process to reactive.
Besides, acute L. it is, as a rule, characterized by the anemia and thrombocytopenia flowing quite often with a hemorrhagic syndrome that is not present at inf. mononucleosis.
Acute L., proceeding with a pancytopenia without blast cells in blood, it is necessary to differentiate with hypoplastic anemia (see). Also so-called osteoplastic cancer — total metastatic damage of marrow can give a similar picture of blood. The diagnosis is specified by the puncture of marrow finding at acute L. blast cells, and also trepanobiopsiya.
Very seldom there is a need for differentiation of acute promiyelotsitarny L. and the leukemoid test of promiyelotsitarny type proceeding with a hemorrhagic syndrome and dominance of promyelocytes in marrow. Unlike acute promiyelotsitarny L., the leukemoid test of this type proceeds without the expressed thrombocytopenia which is the cornerstone of a hemorrhagic syndrome at acute promiyelotsitarny L. Besides, at acute promiyelotsitarny L. in blood and marrow typical blast cells along with the blast cells having the plentiful granularity making them similar to promyelocytes meet. Gistokhim, the analysis specifies the diagnosis. At leukemoid test (see) atypical there are no blast cells in marrow.
Sometimes there is a difficulty in the differential diagnosis of acute L. and the immune lysis leading to anemia, thrombocytopenia and a neutropenia to a pan-cytolysis. The immune pan-cytolysis is followed by the expressed hemorrhagic syndrome and slow inf. the complications arising in connection with a neutropenia. In blood there can be blasttransformirovanny lymphocytes which it is wrong, especially in a thick blood film, it is possible to take for blasts. However in materials of a puncture and trepanobiopsiya at an immune lysis, unlike acute L., marrow polimorfen, contains many megacaryocytes and does not contain typical blast cells, tests on antibodies to erythrocytes and thrombocytes are sharply positive.
Treatment. At acute L. urgent hospitalization is shown to patients. Treatment in out-patient conditions is in some cases possible. At acute L. apply pathogenetic treatment — the combined introduction cytostatic means (see), a cut continue, as a rule, to the expressed depression of a hemopoiesis for the purpose of achievement of remission. Combinations of drugs which are used according to the corresponding schemes of treatment are offered. The most known combinations: VAMP (combination of Vincristinum, Amethopterinum methotrexate, 6 Mercaptopurinum and Prednisolonum); SOAR (Cyclophosphanum, Oncovinum, arabinozid-tsitozin, Prednisolonum); «7 + 3» and «5 + 2» (to seven - or the five-day course of an arabinozid-tsitozin, during the first 2 or 3 days is entered rubomitsin); POMP (Purinetholum, Oncovinum, methotrexate, Prednisolonum; at the same time Oncovinum is entered in a usual dose, other three drugs within 5 days in very high doses); TsVAMP (Cyclophosphanum, VAMP with addition). Apply also combinations of tsitostatik: rubomitsin with Prednisolonum; Cytosarum with Vincristinum, Cyclophosphanum and Prednisolonum, etc.
E.g., effective and, to a certain extent, sparing at a miyeloblastny form of acute L. the 8-day scheme VAMP is: in the first and fourth days of treatment enter intravenously Amethopterinum methotrexate (20 mg/m 2 ); for the second day — Vincristinum (2 mg/m 2 ) enterally; daily — 6 Mercaptopurinum (60 mg/m 2 ) and Prednisolonum (40 mg/m 2 ) enterally. Repeat a course in 9 days. This scheme of treatment allows to receive remission at 30 — 40% of patients 25 years are more senior.
Use of tsitostatik according to schemes in combination with rubomitsiny causes remission of acute promiyelotsitarny L in 50 — 60%.; in some cases another recurrence can be stopped before the applied means if they were effective. Treatment of other forms of acute L. it is carried out by the same principles and the same means about which it is told above, except for a low-percentage form. Treatment of a low-percentage form of an acute leukosis is usually performed by Prednisolonum and 6 Mercaptopurinum.
Active use of cytostatic means leads in some cases to sharp oppression of a normal blood formation, development of heavy infectious complications and progressing of leukemic process.
Cytostatics have considerable side effect on normal fabrics, the epithelium went. - kish. path, liver, closed glands, c. N of page, cardiac muscle, peripheral nerve fibrils; the peculiar polysyndromic disease (A cytostatic disease) demanding additional to lay down develops. actions.
3. A. Korobchenko et al. (1971) for the purpose of prevention inf. complications suggest to place the patient to acute H.p. deep neytropenny (leukocytes less than 1000 in 1 mkl) in sterile (aseptic) chamber. Air in such chamber during 16 hours is irradiated with black light lamps, the medical staff at an entrance to the patient shall put on a sterile dressing gown, boot covers, a hat and a mask and to process hands solution of chloroamine.
In some cases use the sterile daily replaced linen for the patient and will sterilize food by processing it under pressure. At development of a necrotic enteropathy in some cases it is reasonable to apply «sterilization» of intestines by regular intake of mix of not absorbed antibiotics.
The most important moment of a maintenance therapy in the period of a miyelodepressiya is adequate replacement therapy by cellular components.
For stopping of bleeding use transfusion of freshly cooked trombotsitny weight (see), received from one izogruppny donor. For the purpose of correction of a hemorrhagic syndrome apply also Trasylolum, Contrykal and other hemostatics. For fight against anemia use transfusion eritrotsitny weight (see). At an agranulocytosis a crucial role in the prevention inf. complications an antibioticotherapia plays. Efficiency of transfusion leykokontsentrata (see) it is not really high.
The possibility of use at L is studied. transplantations of marrow (see). Transplantation is possible from HLA-and MLC-combine-mykh donors (from brothers and sisters, from enzygotic twins) after preliminary cytostatic training of the recipient, napr, high doses of Cyclophosphanum, with the subsequent total body irradiation. The recipient shall be in sterile chamber; fight with inf. by complications it is carried out by means of antibiotics of a broad spectrum of activity and a transfusion of leukocyte weight; the hemorrhagic syndrome is stopped by transfusion of trombotsitny weight.
On reaching full remission at acute L. in a hospital sometimes conduct an additional course of polychemotherapy for the purpose of consolidation of remission, then transfer the patient to out-patient treatment cytostatic drugs in maintenance doses with periodic cycles of a reinduktion of remission.
Increase in quantity of blasts in marrow or emergence them in blood, other symptoms of a recurrence of L. demand urgent resuming of intensive polychemotherapy.
At a myelosis tumoral process is surprised granulotsitarny, monocytic, platelet and erythrocyte sprouts of marrow. The ancestor of a tumor — a cell predecessor of a myelopoiesis. Process can extend to a liver, a spleen, and in a thermal stage any fabric can be surprised.
At the beginning of the developed stage the patient has no complaints, the spleen is not increased or slightly increased. The composition of peripheral blood is only slightly changed. In this stage the diagnosis can be established by the analysis of the «unmotivated» nature of a neutrophylic leukocytosis with shift in a leukocytic formula to myelocytes and promyelocytes, detection considerably of the raised ratio of leukocytes and eritrokariotsit in marrow and the «Philadelphian» chromosome in granulocytes of blood and cells of marrow. In a trepanata of marrow already during this period almost full replacement of fatty tissue by myeloid fabric is observed.
Without treatment the developed stage hron, a myeloleukemia is characterized by gradual increase of fatigue, perspiration, sometimes subfebrile condition, the progressing increase in a spleen, is more rare than a liver.
At the correct therapy the condition of patients remains quite satisfactory, they keep in whole or in part working capacity, lead a usual life.
In blood test the neutrophylic leukocytosis (10 000 — 50 000 — 100 000 and above in 1 mkl), shift is observed to the left (to myelocytes, single promyelocytes). Occasionally increase in maintenance of eosinophils, basophiles and thrombocytes meets. The number of erythrocytes and level of hemoglobin in this stage are, as a rule, normal.
Though at this disease granulocytes also ripen to segmentoyaderny forms, breakdown of the chromosomal device (shortening of a chromosome in the 22nd couple with a translocation is more often on the 9th couple) leads to decrease in phagocytal ability of leukocytes, change of a ratio of enzymes in them.
In an end-stage hron, a myeloleukemia gains lines of a zlokachestvennost: high fever, quickly progressing exhaustion, ostealgias, sharp weakness, increase and consolidation limf, nodes, the expressed anemia. As a rule, bystry increase in a spleen is noted, increase in a liver, a gastromenia and intestines, repeated inf is more rare. diseases. Petekhialny rash on skin and mucous membranes, the nasal and gingival bleedings connected with decrease in level of thrombocytes is noted. Necrotic processes (noma, decubituses, trophic ulcers, necrotic quinsies and esophagitis, necroses of intestines) are sometimes observed that it is connected with decrease in quantity of neutrophils in blood.
The most important sign of an end-stage hron, a myeloleukemia is sharp increase in percent of blast cells (in the beginning quite often myeloblasts, and then nondifferentiable blasts) in marrow and blood — so-called blast crisis.
The sharp change during a disease at the time of transition to an end-stage is caused by instability of the chromosomal device of leukemic cells, emergence of cells of more and more malignant clones. Kariologicheski in an end-stage at 80% of patients is defined emergence of aneuploid clones. As well as clinical features of an end-stage, the kariologichesky analysis are shown by transition of a tumor from monoclonal — high-quality what it was in the developed stage, in polyclonal — malignant.
The diagnosis hron, a myeloleukemia and its stage is put on the basis of data of blood, taking into account clinic, results of a puncture and trepanobiopsiya of marrow, and also identification of Ph' - chromosomes.
Treatment hron, a myeloleukemia is carried out by means of cytostatic drugs from the moment of establishment of the diagnosis and morfol, by its confirmations. Criteria of efficiency of this treatment — decrease in a leukocytosis, reduction of a spleen.
In the developed stage hron, a myeloleukemia therapy by Myelosanum on 2 — 4 — 6 mg a day (enterally) depending on quantity of leukocytes in blood is most effective. It is carried out on an outpatient basis. At inefficiency or intolerance of Myelosanum use miyelobromol. This drug is especially shown at the expressed splenomegaly though in this case therapy of the choice is radiation of a spleen; hexaphosphamide can be applied.
Treatment by cytostatics is carried out under control of regular blood tests with obligatory calculation of thrombocytes.
Upon transition hron, a myeloleukemia in an end-stage use the combinations of tsitostatik applied usually to treatment of acute leukoses.
Sometimes at the beginning of an end-stage it is effective miyelobromol. According to indications carry out treatment inf. complications and hemorrhagic syndrome. At sharp increase in group limf, nodes, a spleen or local ostealgias telegamma therapy is shown (see. Gamma therapy ). The forecast of a disease is defined by a stage. At the correct treatment the developed stage can proceed on average apprx. 4 years, 5 — 10 years are frequent. Longevity of patients in an end-stage even at the combined polychemotherapy usually does not exceed 6 — 12 months.
The option of a myelosis which is observed in 2 — 5% of all cases without Ph '-chromosomes differs in bigger weight.
The chronic lymphoid leukosis (hron, a lymphadenosis, hron, limf, leukemia) represents a benign tumor of immunocompetent fabric, a basis a cut — morphologically end-stage lymphocytes. The ground mass of cells at hron, a lymphoid leukosis is made by V-lymphocytes (80 — 98%), but also forms of a disease with T-lymphocytic proliferation are known.
On a current distinguish two stages of a disease: developed (high-quality) and terminal (malignant), at a cut process is transformed or to acute L., or in sarcoma; however the second stage can not be. The disease more often at advanced age is shown.
It is frequent to define an onset of the illness happens it is almost impossible: among full health and in the absence of any unpleasant subjective feelings in blood the small, but incremental lymphocytosis is found in the patient. At early stages the number of leukocytes can be normal, then in process of increase of percent of lymphocytes also the leukocytosis grows. In rare instances the onset of the illness is shown by a lymphocytosis at unsharp decrease in level of leukocytes. At increase of number of leukocytes to several tens of thousands in 1 mkl blood are usually noted also subjective disturbances: moderate weakness, perspiration, increased fatigue.
Increase in the sizes limf, nodes (as a rule, on a neck) is a characteristic symptom of a disease which is sometimes noted right at the beginning, in other cases joins later., the Frequent symptom — increase in a spleen, increases a liver less often.
In blood along with increase in percent of lymphocytes, presence of single prolymphocytes and sometimes rare lymphoblasts it is quite often possible to note characteristic for hron, a lymphoid leukosis of a so-called shadow of Gumprekht — the kernels of lymphocytes destroyed at preparation of a smear in which among glybok chromatin it is possible to notice nukleola. At symptomatic lymphocytoses (behind an exception inf. a lymphocytosis) Gumprekht's shadows usually do not meet. In the developed stage of a disease the absolute content in blood of neutrophils, thrombocytes and erythrocytes can remain many years on datum level.
Marrow is histologically characterized by diffusion or focal growth of lymphocytes. In punctate the high percent of lymphocytes is found. However this sign can be the authentic evidence of tumoral proliferation in marrow only at low percent of lymphocytes in blood, otherwise for diagnosis of L. it is more preferable to use not a puncture, but a trepanobiopsiya of marrow or to combine both researches.
In the developed stage of a disease the main complications hron, a lymphoid leukosis come to light: autoimmune cytolytic processes and various inf. complications. The autoimmune cytolysis concerns all three sprouts. However there is an autoimmune erythrocytolysis and thrombocytes more often. In some cases autoantibodies are directed against eritrokariotsit. At the same time and eritrokariotsit in marrow it can not be noted increase in level of bilirubin, characteristic of hemolysis, reticulocytes in blood. On the contrary, disappearance of reticulocytes from blood and extremely low interest of eritrokariotsit in marrow is observed. The autoimmune nature of hemolysis can be confirmed with direct positive test of Koombs (see. Koombs reaction ), agregatgemagglyutinatsionny test.
The oppression of humoral immunity characteristic for hron, a lymphoid leukosis and being a consequence of a depression of a normal lymphopoiesis, is shown inf. complications (pneumonia, quinsies, etc.) which are the most frequent cause of death of patients.
A terminal exacerbation of a disease in the form of transition to acute L. or sarcoma meets at hron, a lymphoid leukosis it is rather rare though in process of lengthening of life of patients the frequency of transition increases. Acute L. in an end-stage hron, a lymphoid leukosis has no specific features, changes in a leukocytic formula — growth of percent of blast forms at simultaneous oppression of cells of normal sprouts can be its first signs.
Developing of sarcoma is characterized by emergence of a dense tumor more often in the field of one of limf, nodes. Development of a lymphosarcoma can be followed by reduction of the sizes which are not struck with sarcomatous process limf, nodes, change of a lymphocytosis by a neutrocytosis.
The special form hron, a lymphoid leukosis is represented by a hairy cell leukosis, at Krom lymphocytes have a row morfol, differences: outgrowths of cytoplasm in the form of fibers, homogeneous, sometimes from nukleola, the kernel reminding a kernel of a blast; cytoplasm of these cells contains a lot of acid phosphatase, steady to tartarikovy to - those. On immunol. to features «hairy» lymphocytes belong to B-cells though also T-lymphocytic options of hairy cell L are described. At the same time on a nek-eye to properties in particular on weak ability to phagocytosis, these cells remind monocytes. For a wedge, pictures of hairy cell L. increase in a spleen, quite often considerable, lack of increase peripheral limf, nodes, the expressed cytopenia is characteristic.
Independent form hron, a lymphoid leukosis is so. naz. a form César and, characterized by damage of skin. Process begins quite often with emergence of a skin itch, then limf, infiltrates in skin which can be local, and then affect skin is total, being located under epidermis; gradually (sometimes early enough) the lymphocytosis or percent of ugly lymphocytes in blood accrues. Lymphocytes at Cesaria's form are larger than usual, have a kernel of looped structure, quite often ugly with the wrong contours. Their belonging to T lymphocytes is proved. The lymphadenopathy can be the mixed nature: one limf, nodes are increased reaktivno in response to damage of skin, others — owing to leukemic infiltration. The spleen quite often increases already in the course of a disease.
Diagnosis hron, a lymphoid leukosis establish on the basis of increase in percent of lymphocytes in blood and limf, proliferation in marrow.
Biochemical, the blood analysis at early stages of a disease, as a rule, does not find specific changes. Development of a disease is followed by decrease in the general level of gamma-globulins, in rare instances perhaps monoclonal increase in gamma-globulins. Sometimes also polyclonal increase in gamma-globulins meets. Need for differentiation with other diseases arises sometimes at the initial diagnosis hron, a lymphoid leukosis when the lymphocytosis is observed at normal or even a little reduced level of leukocytes in blood and nodes on a neck are moderately increased only separate limf. Can give a similar picture inf. mononucleosis. Assessment of a smear of peripheral blood helps with the differential diagnosis: at inf. a mononucleosis, unlike a lymphoid leukosis, polymorphism of lymphocytes is expressed, the basophilia and existence of a wide rim of cytoplasm is noted, at the same time there are no Gumprekht's shadows. If it is about patients more young than 25 years, the assumption about hron, a lymphoid leukosis it is possible to exclude and think, as a rule, about inf. a mononucleosis (see. Mononucleosis infectious ) or limf, reactions to implementation of a virus (see. Lymphocytosis acute infectious ).
Difficulties in diagnosis of a chronic lymphoid leukosis can arise at development of inflammatory process in a leukemic limf, a node at a low leukocytosis. It is possible to specify the diagnosis as a result of overseeing by the patient after an antibioticotherapia.
At increase in one group limf, nodes and lack of a leukocytosis hron, the lymphoid leukosis should be differentiated with a lymphosarcoma. In this case the diagnosis allows to establish gistol, and tsitol, a research limf, a node, in Krom at hron, a lymphoid leukosis the diffusion growth of mature cells (lymphocytes) is found, as a rule, and at to a lymphosarcoma (see). — blast cells. In punctate of marrow at this stage hron, a lymphoid leukosis still can not be a high lymphocytosis.
For treatments hron, a lymphoid leukosis apply Chlorbutinum (leukeranum, hlorambutsit), sometimes in combination with Prednisolonum. Indications for steroid therapy at hron, a lymphoid leukosis are the general or partial cytopenia, autoimmune hemolysis or thrombocytopenia, and also inefficiency of other cytostatic therapy.
Steroid therapy at hron, the lymphoid leukosis proceeding without immune complications during a long term and without use of cytostatic drugs is contraindicated. Except leukeranum, leukeranum in combination with Prednisolonum, treatment by Cyclophosphanum is effective (200 — 400 mg a day intramusculary or inside). At inefficiency of these drugs apply Photrinum and pafentsit.
At significant increase and relative density peripheral limf, nodes, during the involvement in process limf, nodes of an abdominal cavity, increase in a liver there can be effective a combined Cytostatic therapy (schemes VAMP, TsOP).
At a high leukocytosis (200 000 — 300 000 in 1 mkl above) the therapeutic cytapheresis of blood of the patient by means of a separator of continuous current can be applied (see. Plasma exchange ). At an anemia infusions of eritrotsitny weight are shown.
Quite widely at hron, a lymphoid leukosis apply radiation of a spleen, limf, nodes and skin at their defeat. The direct indication to radiation therapy is the leukemic infiltration of nervous trunks which is followed by a pain syndrome. Moderate exposure doses of a spleen lead not only to its reduction, but also to decrease in a leukocytosis and reduction of peripheral lymph nodes. Apply also a method of general irradiation.
One of methods of treatment of an autoimmune cytopenia is splenectomy (see). Indications for it — falling of level of erythrocytes or thrombocytes, not korrigiruyemy a high dose of corticosteroids. Negative direct test of Koombs does not allow to exclude the immune nature of anemia and is not a contraindication to a splenectomy at hemolysis since she is positive only in 50% of cases.
At a hairy cell leukosis the good effect is observed from use of steroid hormones and a splenectomy.
At hron, a lymphoid leukosis prevention and treatment inf has special value. complications. As antibacterial drugs apply antibiotics in the maximum doses.
At hron, a lymphoid leukosis patients usually keep for a number of years satisfactory health and working capacity. Treatment is generally carried out on an outpatient basis.
The chronic monocytic leukosis occurs at persons 50 years are more senior. Increase peripheral limf, nodes usually is not observed; in 50% of all cases the spleen is palpated.
Long safe current hron, monocytic L. can be replaced, as well as at other forms hron. L., an end-stage of a disease, the shown blast crisis, thrombocytopenia with a hemorrhagic syndrome, growth of a spleen.
Hron, monocytic L. it is characterized by the high content (20 — 50%) of monocytic cells in blood at the normal or a little raised leukocytosis. Along with mature monocytes in blood also single promonocytes can meet. The typical blast structure of a kernel usually is not observed. Characteristic lab. an indicator at this form L. high concentration of a lysozyme in blood and urine of patients and positive reaction to an alpha naftilesterazu in monocytoid cells is. In blood of patients single eritrokariotsita can meet. ROE accelerates, as a rule, early and considerably, anemia is usually noted.
The considerable monocytosis in marrowy punctate is observed seldom; trepanobiopsiya with a diffusion arrangement of large mononuklear, almost full replacement of fatty tissue, as a rule, reveals a polymorphocellular hyperplasia of marrow.
Differential diagnosis is carried out with tuberculosis, cancer, Valdenstrem's macroglobulinemia at which the monocytosis is observed too; in doubtful cases dynamic overseeing gematol, indicators is necessary.
Process a long time does not demand any treatment, in some cases treatment is carried out by means of the small doses of Prednisolonum usually sufficient for maintenance gematol, by compensations. In an end-stage therapy does not differ from that at other forms acute L.
Hron, monocytic L. differs in a long-term quiet current, however the frequency of infectious complications at it gradually increases.
The chronic erythremic myelosis is characterized by the progressing normokhromny anemia, slight increase in blood of number of reticulocytes, existence of eritrokariotsit, quite often myelocytes, promyelocytes, and also blasts, a hyperplasia of a red sprout in marrow, is frequent with megaloblastoid lines, refractory to therapy by B12 vitamin. The erythremic myelosis comes to an end with blast crisis.
In the presence of the accompanying myelofibrosis speak about an essential form hron, Vagan's erythremic myelosis.
In the developed stage apply treatment by Prednisolonum (20 — 40 mg a day), at a stage of blast crisis — the combined chemotherapy, as at acute L.
A clinical picture, the diagnosis, treatment and the forecast of a macroglobulinemia of Valdenstrem, a multiple myeloma, an erythremia, hron, a subleukemic myelosis — see. Valdenstrema disease , Multiple myeloma , Osteomyelofibrosis , Polycythemia .
Neuroleukaemia (leukemic defeat of a nervous system) — one of frequent complications of L. Nablyudayetsya is more often at acute lymphoblastoid L. at persons 15 years are younger, is much more rare at other forms of acute L. and in an end-stage hron. L.
Developing of neuroleukaemia is caused by innidiation of leukemic cells in covers of a head and spinal cord. Histologically in superficial departments of an arachnoid membrane leukemic infiltrates come to light. At destruction of trabeculas of an arachnoid membrane leukemic cells get to a subarachnoid space and are found in cerebrospinal liquid. Much less often infiltrates from blast cells in substance of a brain meet.
In some cases there is a leukemic infiltration of peripheral nerves with various motive and sensitive disturbances.
Wedge. the picture of neuroleukaemia consists of a meningeal and gipertenzionny syndrome. The persistent headache, repeated vomiting, slackness, irritability is noted. Hypostasis of disks of optic nerves, nystagmus, squint and other signs of damage of cranial nerves, Meningeal symptoms comes to light. At such clinic usually in cerebrospinal liquid the expressed blast cytosis is observed.
Due to the impermeability of a blood-brain barrier for the majority of tsitostatik treatment of neuroleukaemia is performed by endolumbar introduction of cytostatic means. The most effectively endolumbar introduction of a methotrexate with arabinozid-tsitoziny. During remission conduct the special preventive course including radiation of the head in a total dose of 2400 I am glad also 5-fold introduction of a methotrexate endolyumbalno.
In the presence of leukemic infiltrates in substance of a brain endolumbar introduction of himiopreparat and radiation can be ineffective. If there is a recurrence against the background of continuous therapy, then it always means a new stage of a tumoral progression and demands change of the scheme of treatment.
Skin displays of leukoses
Skin manifestations of L. are divided into two groups differing on the morfol, a structure. Refer skin manifestations, a wedge to the first, and gistol which picture has no specific to L. features. Defeats of this group are named by Audrey (S. Audry, 1902) leukemids; some authors use this term for designation of any skin manifestations at L.
Nonspecific damages of skin can be a toksiko-allergic origin and be expressed by a skin itch, an erythema, violent rashes, a small tortoiseshell; they can be caused by insufficiency of a hemopoiesis and be expressed by development of a hemorrhagic syndrome with hemorrhages in skin (from petechias to drain extensive ecchymomas), pallor and yellowness of the skin tied with hemolysis of erythrocytes; at last, they can arise in connection with decrease in the general and immunol. body resistance and then are shown by development of pustulous and fungal infections of skin, the surrounding herpes, the ulcer and necrotic changes which are not connected with leukemic proliferation.
Specific damages of skin, patogistol concern to the second group. which basis corresponds to changes in the hemopoietic bodies. For the first time leukemia with this-tsifichesky damage of skin was described by Besyadetsky (A. Biesiadecki, 1876). A bit later Filippo (Philippaut, 1880) reported about the woman, sick leukemia, at a cut on the head and a face there were large nodes creating a picture of «a lion's muzzle» (facies leonina). Described similar observation in 1885 of M. Kaposha under the name «Jymphodermia perniciosa».
Specific damages of skin are shown in the form of nodular and knotty educations (fig. 15 and 16), ulcer and necrotic changes owing to destruction of a leukemic proliferat, diffusion defeat in a type of a partial or full erythrosis.
Specific ostrovospalitelny processes in skin, the violent, simulating impetigo of a rash (fig. 17), a disease of Dyuringa, a furunculosis are characteristic of an acute leukosis. More rare than a rash of rozeolezno-papular character, in the form of an erythrosis, and also nodes of light pink or cyanotic-crimson color of a plotnovaty consistence, slightly painful with a peeling on a surface.
To specific damages of skin at hron. L. lines hron, an inflammatory dermatosis are inherent: affected areas of skin are painted in congestive (cyanotic-pink, brown) tone, considerably infiltrirovana (like flat infiltrates), quite often lichenified, are shelled. Damage of skin as an erythrosis is characteristic of a chronic lymphoid leukosis. Skin at the same time of red color with a brownish or cyanotic shade, is lichenified, dry, reminds leather of an elephant, with small - or a macrolaminar peeling. Against the background of an erythrosis there can be nodes and plaques differing in more saturated coloring and density. On sites of big infiltrates hair follicles, grease and sweat glands usually are absent.
The surrounding herpes affects more often than patients hron, a lymphoid leukosis and takes the unusual form — gangrenous or generalized, differing in a long and heavy current.
Found at various L. gistol, changes of skin are quite often very similar, the main difference consists in cellular structure of a proliferat.
For acute L. infiltrates in skin and especially in hypodermic cellulose which cellular part mature cells of a myeloid row are generally unripe and to a lesser extent are characteristic. At hron, a myeloleukemia, except dense accumulations of cells of a myeloid row in skin and hypodermic cellulose, the small groups of cells extending in the form of couplings perivaskulyarno and around sweat glands are observed. Except cells of a myeloid row, eosinophils and undifferentiated cellular elements are a part of infiltrates. Under nipples of skin the narrow zone, free from infiltrate comes to light.
At a lymphoid leukosis infiltrates in skin consist of round, lymphocytic cells, not distinguishable practically from normal lymphocytes, and a small number of lymphoblasts. On border of infiltrate also plasmocytes are observed not numerous reticular.
Skin manifestations of L. it is necessary to distinguish from the changes of skin connected with treatment of sick L. cytostatic and hormonal drugs, radiation and by other methods, from a hemorrhagic vasculitis (see. Shenleyna — Genokh a disease ), impetigo (see), diseases of Dyuringa (see. Dyuringa disease ), and also from high-quality skin lymphoid giperplaziya, shaped small knots. The last group includes Shpigler's sarcoid — Fendta (see. Sarcoidosis ) and lymphocytoma of skin (see). The differential diagnosis is based on gematol, data, on character a wedge, and gistol, pictures of defeat.
For treatment of damages of skin at L. apply Castellani's liquid and corticosteroid ointments (Prednisolonum, Synalarum, etc.), a local roentgenotherapy.
Features of leukoses at advanced and senile age
At advanced and senile age are more often observed a low-percentage form of acute L., hron, lymphoid leukosis, hron, monocytic L. and multiple myeloma. At advanced age acute L. give full remissions much less often, however in the conditions of the constraining therapy life expectancy of patients can be quite big. At persons 60 years are more senior the long-term quiet current hron, a myeloleukemia, sometimes — acute L is noted., low-percentage and other forms.
At this age patients transfer anemization) heavier, quite often shown first of all a circulatory unefficiency. Therefore at advanced and senile age at decrease in hemoglobin it is lower than 50% to lay down along with others. actions special value hemotransfusionic therapy, especially has transfusions of eritrotsitny weight.
a Certain value at L. has a radiological method of a research, especially when a wedge, and gematol, symptoms of a disease (e.g. are insufficiently expressed, at L., proceeding with symptoms of polyarthritis and an aleukemic picture of blood).
Specific changes of bones of a skeleton radiological are found in adults in 45 — 50% of cases. They are localized preferential in a diaphysis of long tubular bones, but can be revealed also in flat short bones. Most often changes have an appearance of the small centers of destruction of an oblong and oval form (fig. 18). In some cases sites of destruction of the big sizes, take all thickness of a bone (fig. 19). Changes in a skeleton can be followed by formation of longitudinally разволокненной (fig. 20), shirokopetlisty, chaotic structure of the bone substance or a diffusion porosis which sometimes is shown only the underlined rough line of a hip (linea aspera femoris, fig. 21). Well-marked linea aspera femoris at development osteoporosis (see) contrasts with the neighboring sites of a diaphysis better that can help earlier identification of the begun depression of tissue of femur.
From flat and short bones vertebrae most strongly are surprised: in addition to a porosis, in them compression changes can be found. Changes in bone system at L. at children come to light more often (approximately in 80 — 90% of cases) and are more expressed; changes of bone and joint system can prevail in a wedge, a picture, and in an initial phase of a disease sometimes to be the only display of a disease, simulating acute joint rheumatism, osteomyelitis etc. Besides, children often have periostoses and cross strips of depression in metaphyses on border to an epiphyseal cartilage.
Changes in bodies of a thorax at L. can be caused by a basic disease (the leukemic nature) or accompanying (pneumonia, tuberculosis, a candidiasis), the L which are often complicating a current. Leukemic defeats in bodies of a thorax are observed at all forms of a disease. Character and their expressiveness depend on a form L., jokes of a course of process and age of the patient.
At acute L. leukemic changes in bodies of a thorax meet more often in the form of a tumor of a mediastinum, a hyperplasia intrathoracic limf, nodes, damage of lungs, a pleura. The tumor of a mediastinum comes to light at acute lymphoblastoid L more often. at children's age. At acute forms L. the tumor of a mediastinum is found in adults much less often and is observed generally at acute lymphoblastoid L. and not a differentiable form of acute L. Rentgenologicheski the tumor is located in a front mediastinum and is characterized by expansion of a median shadow in both parties. Its contours can be straightened or polycyclic. The tumor of a mediastinum is quite often combined with a hyperplasia intrathoracic limf, nodes and peribronchial leukemic infiltration in radical zones. Tumors of a mediastinum at acute leukoses are extremely sensitive to radiation therapy and antineoplastic means.
Increase intrathoracic limf, nodes meets preferential at acute lymphoblastoid L. Chashche it is combined with other leukemic changes (a tumor of a mediastinum, damage of lungs). However also the isolated involvement in process of any group limf, nodes is possible.
Specific changes in lungs at acute L. consist in infiltration of tissue of lung, tending to distribution during the progressing of a disease. Formation of massive blackouts (fig. 22) forming from the merging centers against the background of the expressed interalveolar or peribronchial leukemic infiltration is characteristic. Large tumorous formations or the multiple centers of consolidation can be found, it is frequent against the background of the strengthened and deformed pulmonary drawing. In some cases the rough tyazhistost caused by peribronchial or perivascular leukemic infiltration, or a leukemic limfangiit is noted; sometimes there are multiple heart attacks of a lung caused by thrombosis of vessels leukemic cells.
Focal or infiltrative changes can be followed by formation of cavities owing to a necrosis and disintegration of fabric. Atelectases are observed extremely seldom thanks to preferential peribronchial distribution of leukemic infiltration.
Leukemic damage of a pleura is followed by its thickening and formation of massive pleurisy. Characteristic symptoms of leukemic pleurisy — unilateral, persistent, despite repeated evacuations, accumulation in a pleural cavity of hemorrhagic exudate.
At patients hron, a lymphoid leukosis of change of bodies of a thorax are characterized by a hyperplasia intrathoracic limf, nodes. The tumor of a mediastinum meets extremely seldom, hl. obr. in the final of a disease against the background of sharp progressing of a disease, a thicket is located directly behind a breast, has the semi-oval form, adjoining the wide basis a breast. Defeat of pulmonary fabric, according to various authors, is found in 20 — 38,5% of cases. Infiltrative forms with disintegration and peribronchial infiltration prevail. Damage of a pleura is observed seldom.
At hron, a myeloleukemia leukemic changes in bodies of a thorax radiological come to light considerably less than at acute L. and hron, lymphoid leukosis. The tumor of a front mediastinum can arise only at long disease in the period of blast crisis. In certain cases nodes increase intrathoracic limf. There are no large leukemic infiltrates or tumoral nodes in lungs, as a rule. Leukemic infiltration, being located on the course of small vessels and interalveolar partitions, reveals a picture of strengthening of the pulmonary and vascular drawing of melkopetlisty character.
Leukemic changes in bodies of a thorax should be differentiated with the accompanying processes in pulmonary fabric: pneumonia, candidiasis and tuberculosis.
The pneumonia which is observed at sick L., treat bronkhopnevmoniya of fibrinous and hemorrhagic type. In some cases preferential infiltrative changes in a type of focal segmented and share defeats radiological come to light. They are unilateral, differ in a long current, slow rates of involution (up to 3 months), often recur, have bigger tendency to disintegration and a complication pleurisy. Such pneumonia is equally often observed at acute and hron, a lymphoid leukosis. Sometimes pneumonia multiple melkoochagovye, focal and intersticial type. They, as a rule, are widespread, bilateral, clinically proceed with the phenomena of the increasing pulmonary insufficiency. This pneumonia, as a rule, does not recur and has considerably smaller tendency to emergence of complications in the form of disintegration of pulmonary fabric and pleurisy, is more often observed at hron, a myeloleukemia and is much more rare at acute and hron, a lymphoid leukosis. Permission of such pneumonia, irrespective of a form L., on average comes during 2 — 4 weeks.
Differential diagnosis between leukemic and inflammatory changes in lungs is difficult and is based on all complex kliniko-rentgenol, given taking into account dynamics of process and a form L. Focal and infiltrative changes and rather bystry dynamics of process are more characteristic of pneumonia. Leukemic infiltration differs in preferential intersticial changes in the beginning, accrues slowly, the wedge proceeds without noticeable, or is more rare than manifestations with the phenomena of pulmonary insufficiency.
Control rentgenol, researches in such cases are conducted in 2 — 4 days at the obligatory account initial rentgenol, data.
A candidiasis which can complicate a current of L., it is characterized by bystry increase and roughness of the expressed focal, infiltrative changes in lungs, their bystry distribution on different departments of lungs, extensive disintegration of pulmonary fabric. The diagnosis is confirmed bacterial, a research of a phlegm.
Leukemic changes in pulmonary fabric and in intrathoracic limf, nodes should be differentiated with their tubercular defeat.
The gastrointestinal tract disease is observed at acute and hron. L. lymphoid type. At acute and hron. L. myeloid type leukemic changes in went. - kish. a path meet seldom. At these forms of a disease develop secondary necrotic more often - the cankers caused areactivity]» an organism and the carried-out cytostatic therapy. Leukemic defeat went. - kish. a path it is characterized by early simultaneous involvement in process of various departments, napr, a stomach, a bulb of a duodenum and a caecum with final department of ileal. Radiological changes in a stomach and a duodenum can be in the form of polipoobrazny protrusions of a mucous membrane (fig. 23) or limited flat discal thickenings of walls of a stomach, large tumoral educations and sharply reinforced raised folds of a mucous membrane; the peristaltics is kept or weakened. Local or diffusion infiltration of a wall of a gut can lead to perforation, a stenosis and impassability. Leukemic infiltration of a stomach and intestines is observed also at an aleukemic phase of a disease that creates difficulties in recognition of the nature of these changes. Simultaneous defeat of a bulb of a duodenum, stomach, and is frequent and intestines demonstrates leukemic infiltration. Rentgenol, data if necessary are confirmed by endoscopy and a biopsy from the struck department went. - kish. path.
at the heart of radiation therapy of L. high radio sensitivity of leukemic cells lies. Radiation therapy is usually applied in combination with chemotherapy. At acute L. radiation therapy is applied to prevention of a neuroleukosis for the purpose of impact on local leukemic infiltrates (in a nervous system, upper respiratory tracts); total radiation can precede bone marrow transplantation. At hron, a lymphoid leukosis radiation is shown in cases of increase limf, nodes, the expressed splenomegaly which are followed by development of a tsitopenichesky syndrome. At hron, a myeloleukemia radiation therapy is shown at much to the increased spleen if Cytostatic therapy is insufficient, and also in the presence of extra marrowy leukemic infiltrates (in skin, a periosteum) and a prelum of vitals the increased spleen.
Limf, nodes irradiate from one or two fields which sizes correspond to the size of tumoral conglomerates. Single focal doses 100 — 150, and at resistant forms — 200 I am glad. Total doses — 1000 — 2000, are more rare 3000 is glad. Radiation is carried out daily. Mediastinal, mezenterialny and retroperitoneal limf, nodes irradiate from front and back fields with the sizes of 10 X 15 cm.
A spleen at hron. L. irradiate depending on its size from one or several fields with the sizes 10 X 12 or 12 X 14 cm; in process of its reduction in process of treatment the number and the sizes of fields reduce. Single focal doses differ in big variability that is connected with various degree of radio-sensitivity of leukemic cells: with 25 they can be glad are increased to 150 I am glad. Daily irradiate one field. The total dose in each case is individual and depends on indicators of blood and rates of regression of a spleen: the therapeutic effect can be gained at doses 200 — 400, sometimes 1000 — 2000 and 3000 is glad.
Big care radiation of upper respiratory tracts and almonds because of a possibility of development of asphyxia, napr, as a result of hypostasis demands, formation of strictures. It is carried out from side fields in a single dose 25 is glad daily or every other day; gradually single dose is increased to 75 — 100 I am glad. Total doses vary from 300 to 3000 is glad.
Beam prevention of neuroleukaemia at patients with an acute lymphoblastoid leukosis is performed during remission. The brain and its covers irradiate from two side fields with the sizes of 20 X 15 cm in a single daily dose 150 is glad to a total focal dose of 2500 is glad. The leukemic infiltrates of cellulose of an orbit and an eye observed at acute L., irradiate two times a week in a single dose 30 I am glad to a total dose 540 is glad. For these purposes use also electronic radiation of accelerators or korotkodistantsionny rentgenoterapevtgichesky devices; a weekly single dose in the center 75 I am glad, total — 225 I am glad; the sizes of fields shall correspond to the sizes of infiltrates.
MEDICAL EXAMINATION AND REHABILITATION
Patients hron. L. are, as a rule, on out-patient treatment. In most cases even the patients receiving cytostatic therapy do not need release from work, but shall be under constant dispensary observation. The sparing mode is recommended. It is necessary to approach carefully the direction in sanatoria and rest houses to the southern regions of the USSR of patients hron. L. in the developed stage. Thermal physiotherapy is contraindicated to them (UVCh, hot bathtubs, etc.) and insolation.
At suspicion on acute L. do to the patient a sternal puncture and at confirmation of the diagnosis immediately direct in gematol, a hospital where it is before achievement of remission. Further the maintenance therapy is carried out on an outpatient basis. Hospitalize the patient in case of development of an agranulocytosis or deep thrombocytopenia. At impossibility to reach remission in a hospital therapy of control of leukemic process sometimes can be performed on an outpatient basis. The issue of working capacity in such cases is resolved individually. In case of permanent disability of patients transfer to disability.
In sick acute L., being under observation of the ambulatory doctor, systematically (it is desirable monthly) the developed blood test including determination of content of thrombocytes and reticulocytes is made.
On the first year of remission the sternal puncture is made once a month, further — time in three months. At suspicion on a recurrence (deterioration in indicators of blood, emergence of blasts, increase limf, nodes, fever, a pain syndrome) the urgent research of marrow and hospitalization of the patient are necessary. At contacts with patients the medical staff is obliged to observe requirements of a deontology carefully.
At acute L. the true diagnosis patients are not told, as a rule. A task of the doctor is the belief of the patient (parents if the patient — the child) in need of continuation of intensive cytostatic treatment according to the program during full remission, carrying out punctures (lumbar, sternal, etc.). Carefully it is necessary to inform the patient on indicators of his blood. Considering weight and duration of polychemotherapy, a possibility of complications, it is necessary to aim to adjust the patient optimistically, orienting it to need of systematic carrying out inspections and courses of treatment.
Patient hron. L., considering rather favorable forecast, in most cases report the diagnosis, emphasizing high quality of process. Similar information helps patients to belong to long chemotherapy, need of retests of blood and other researches more consciously. It is necessary to focus attention of patients to need to observe the recommended mode for the purpose of the prevention of complications.
LEUKOSES AT CHILDREN
L. at children makes a considerable part of malignant new growths. Acute L are more often observed., hron, forms — are much more rare.
At an acute leukosis at children tsitol, options same, as at adults. The most frequent form of acute L. at children's age — acute lymphoblastoid L., other forms meet less often: miyeloblastny, promiyelotsitarny, miyelomonoblastny, monoblast L., erythremic myelosis.
As a result of studying of surface markers of T lymphocytes by means of spontaneous rosetting and B-lymphocytes by definition of surface immunoglobulins by method of an immunofluorescence the following ratio of sub-options of lymphoblastoid L comes to light. at children: T-cellular — 13,9%, V-cellular — 3,4%, O-cellular — 82,7%.
During an acute leukosis at children allocate the same stages, as at adults. The acute stage at most of children has the sudden beginning; the earliest symptom — ostealgias. More often tubular bones (diaphysis), especially femoral and tibial are surprised, the backbone (brevispondiliya) can be surprised. At some children the joint syndrome is noted (joint pains, sometimes in combination with a swelling of fabrics and erubescence in joints). Radiological in bones small destructive ochazhka, osteoporosis and sometimes periosteal reaction are found.
Frequent symptom of acute L. children have an increase limf, nodes: cervical, submaxillary, axillary, inguinal; are sometimes observed a so-called symptom complex of Mikulich — emergence of leukemic infiltration in fabric of salivary and lacrimal glands (see. Mikulich syndrome ), increase limf, nodes of a mediastinum, regarding cases combined with damage of a thymus and followed by short wind, cough. At most of children with acute L. the spleen and a liver are increased.
Leukemic infiltration in skin and hypodermic cellulose can be presented by leukemids from 0,5 to 2 cm in size.
To frequent manifestations of acute L. necrotic damages of skin and mucous membrane of an oral cavity (with development of a leukemic ulitis), and also intestines (a necrotic enteropathy) treat that is caused by leukemic infiltration of fabrics and vessels with the subsequent accession of an infection.
Sometimes, especially at a recurrence of a disease, changes in lungs are found; leukemic infiltration at the same time often is located in an interstitium of lungs and can have diffusion character; physical data correspond to a picture of bronchitis or pneumonia. Radiological the gentle tyazhistost, the small centers as a miliarization comes to light.
At acute L. at children changes from cardiovascular system which are caused often by a myocardial dystrophy at an anemic syndrome can be observed, and also can be connected with leukemic infiltration, necroses and hemorrhages in a cardiac muscle. At the same time borders of heart are expanded, tones deaf, systolic noise is listened. In rare instances the clinic of a leukemic pericardis develops. The diagnosis is specified radiological and elektrokardiografichesk.
A syndrome of neuroleukaemia, the most often observable at a recurrence of acute L. at children, it is characterized by defeat of covers of a brain (leukemic meningitis), covers and substance of a brain (a leukemic encephalomeningitis), a spinal cord with covers and roots of peripheral nerves (leukemic encephalomyelitis). In cerebrospinal liquid find leukemic cells, protein.
At acute L., especially at a recurrence of a disease, increase in testicles at boys and ovaries at girls due to their leukemic infiltration can come to light.
In an initial stage of a disease in marrowy punctate blast cells are present at a small amount (20 — 30%) at safety of erythronormoblastic and megakariotsitarny sprouts. The hypoplastic phase of a marrowy hemopoiesis with decrease in number of myelocariocytes is found in some patients. The quantity of erythrocytes, thrombocytes and leukocytes in peripheral blood can be not changed or moderately reduced.
In the developed stage of acute L. at children in marrowy punctate the number of blast cells is increased (to 70 — 100% of cellular forms), the number of erythronormoblasts, cells of a granulotsitarny row and megacaryocytes is lowered. In blood leukemic blast cells which number can reach 90 — 100% of cellular forms are found. The quantity of leukocytes varies from low figures (leukopenia) to high (20 000 — 100 000 in 1 mkl above). Anemia and thrombocytopenia are noted various degree, with to-rymi manifestations of anemic and hemorrhagic syndromes are connected.
Principles of treatment of acute L. at children same as at adults, also include the following stages: induction of remission by means of poly-chemotherapy; consolidation of remission by carrying out an additional course of intensive chemotherapy and prevention of a neuroleukosis; the supporting treatment with constant use of cytostatic drugs, generally antimetabolites; a reinduktion of remission — periodic carrying out short courses of intensive poly-chemotherapy.
For each of the main options of acute L. there are various programs of treatment taking into account features of a course of a disease.
At children with acute lymphoblastoid L. induction of remission is carried out by daily reception of Prednisolonum (40 mg/m 2 enterally) and intravenous injections of Vincristinum (1,5 mg/m 2 ) once a week (only 4 — 6 injections); in the absence of the expressed effect and to children of early age add rubomitsin (40 mg/m 2 weekly). Endolyumbalno of 1 time in 5 — 7 days enter a methotrexate (12 mg/m 2 ), sometimes in combination with Cytosarum (40 mg/m 2 ), only 3 — 4 times. According to L. A. Makhonova (1977), such scheme of treatment in 90 — 95% of cases causes remission.
The intensive chemotherapy applied by the adult is used in certain cases and for treatment of children. Treat intensive schemes of treatment: the scheme VAMP (Vincristinum on 1,2 mg/m 2 in a week, Amethopterinum methotrexate on 20 mg/m 2 — 1 time in 4 days, 6 Mercaptopurinum on 60 mg/m 2 in day, Prednisolonum on 40 mg/m 2 2 weeks cycles with 2 weeks intervals); schemes TsVAMP, AVAM (VAMP with addition of an arabinozid-tsitozin), TsAP (Cyclophosphanum, arabinozid-tsitozin, Prednisolonum), etc. In certain cases apply the scheme including Prednisolonum (40 mg/m 2 in day within 7 days) in combination with Vincristinum and L-asparaginase (500 — 1000 PIECES on 1 kg of weight a day intravenously within 10 days).
Consolidation of remission is carried out after normalization kliniko-gematol. indicators. At the same time 2 — 3 courses on one of schemes of the combined treatment can be carried out or the complex of the drugs which are not applied at induction of remission can be used: arabinozid-tsitozin (40 mg/m 2 2 times a day, only 8 times from 1st to the 4th day) with the subsequent introduction of Cyclophosphanum (400 — 600 mg/m 2 ) or L-asparaginases (in a daily dose of 200 — 300 PIECES on 1 kg of weight); one L-acnapaginaza within 10 days can be also used (a daily dose of 500 — 1000 PIECES on 1 kg of weight).
For prevention of neuroleukaemia intralyumbalno enter a methotrexate; at some schemes consolidation is completed radiation of the head during 2,5 weeks. Radiation of the head is carried out the open field without trellised diaphragm, a single focal dose — 100 — 110 I am glad, total (for a session) — 200 — 220 I am glad but 5 fractions a week. The total dose happens till 2400 is glad.
The supporting treatment is performed by continuous reception 6 Mercaptopurinums (60 mg/m 2 inside daily), methotrexate (15 — 20 mg/m 2 Once a week). Nek-rym by the patient with the adverse course of a disease Cyclophosphanum can be appointed (200 mg/m 2 Once a week) or combinations of himiopreparat, according to schemes of VAMP or TsOAP, applied with an interval between cycles in 9 — 18 days.
Reinduktion is carried out 1 time in 2 — 4 — 6 months depending on duration of remission according to schemes of induction or consolidation: remissions. Ilo this R. J. Aur et al. (1972) and Spayersa (A. S. Spiers, 1972), carrying out courses of re-induction provides stabilization of remission for the term of more than 5 years at 50% of sick children. The five-year bezretsidivny term of remission is considered adequate to recovery.
At children with acute miyeloblastny L. and other options of a disease induction of remission is carried out use of a combination of an arabinozid-tsitozin (100 mg/m 2 in days intravenously or subcutaneously) with 6 Mercaptopurinum (90 mg/m 2 within 5 days at an interval of 2 weeks) or an arabinozid-tsitozina (100 mg/m 2 within 7 days) with rubomitsiny (45 mg/m 2 within 3 days). It is recommended also rubomitsin (40 mg/m 2 5-day courses with an interval of 7 — 10 days). In some cases apply schemes VAMP, TsVAMP, TsOAP; for achievement of remission carry out 2 — 4 courses. During consolidation and a reinduktion of remission preference is given to a rubomitsin and an arabinozid-tsitozin.
In the program of treatment of acute L. at children include immunol, methods of treatment. Increases in duration of remission reach active immunization by allogenic cryotinned leukemic cells and BTsZh. At emergence of collateral symptoms drugs are temporarily cancelled.
According to indications sick appoint transfusions of whole blood and its drugs or blood substitutes, and also antibiotics, drugs, redoxons, B6, B1, B2, etc. Use of radiation therapy is justified only according to strict indications, in particular in the presence of a compression syndrome and at the expressed leukemic infiltration in bodies.
At 10 — 15% of patients with acute lymphoblastoid L. life expectancy can make over 5 years on condition of carrying out a complex intensive care.
The chronic leukosis at children is most often observed in shape hron, a myeloleukemia; hron, the lymphoid leukosis at children's age does not meet. During hron, a myeloleukemia distinguish the developed and terminal stages. The developed stage of a disease is characterized by the gradual beginning, the child becomes sluggish, complains of a febricula, weakness and bystry fatigue. Gradually the spleen increases, reaching the big sizes, its consistence becomes dense. Occasionally the liver increases. Limf, nodes increase slightly and changeably. Anemic and hemorrhagic syndromes are not observed.
For hron. a myeloleukemia the incremental leukocytosis (with 15 000 to 500 000 in 1 mkl blood above) presented to 85 — 90% by unripe granulocytes — myelocytes, metamyelocytes is characteristic, and it is frequent also single promyelocytes and myeloblasts. Often in blood there is an increase in basophiles and eosinophils — so-called basphilic and eosinophilic association. As a rule, the quantity of thrombocytes to 600 000 — 800 000 in 1 mkl blood increases. The hemoglobin content and quantity of erythrocytes can long remain normal. Tells increase of blast cells in blood and the progressing decrease in quantity of erythrocytes and thrombocytes about transition of a disease to an end-stage, and in a wedge, a picture — bystry increase in a spleen, an ostealgia, fever.
The diagnosis hron, a myeloleukemia can be confirmed with a cytogenetic research, and the chromosome is found so-called Philadelphian (Ph').
The myelosis at children of early age has features: anemia, thrombocytopenia and increase in myeloblasts in blood with lack of the Philadelphian chromosome is often observed (a current on infantile type).
L., arisen within the first 3 months of life, is considered as inborn. Emergence of inborn L. it can be caused by transplacental transfer it from mother, and also hereditary and genetic factors. Most often it is shown in a myeloblast - ache to a form, has the rough, progressing current. In clinic, except the usual symptoms inherent to acute L., extramedullary infiltrates in soft tissues, skin and the expressed splenomegaly are most often noted. The carried-out therapy does not give effect.
Therapy hron, a myeloleukemia in the developed stage is divided on primary constraining, course and supporting. For primary constraining therapy Myelosanum is used (1 — 4 mg of 1 — 3 time a week, depending on a leukocytosis). In the absence of positive effect and expressiveness of «rejuvenation» of composition of blood appoint miyelobromol (125 — 250 mg of 1 — 3 time a week) or hexaphosphamide (5 — 10 mg 1—3 of once a week).
Course therapy is carried out by Myelosanum, miyelobromoly or hexaphosphamide in higher doses. The maintenance therapy is carried out in the period of remission throughout all disease of the same drugs, but in the reduced dose.
Treatment of patients in an end-stage hron, a myeloleukemia is similar to treatment of patients with acute miyeloblastny L.
After the description R. Virkhovom in 1845. L. the person messages on L appeared. animals. In 1858 D. Leisering reported about L. horses, and then described L. pigs, dogs and cows. During the period from 1871 to 1878 Sedamgrotsky (O. of Siedamgrotzky) published several messages on L. dogs, cats, pigs and review on an epizootology of L. cattle. First description of L. mice, appeared in 1878, belongs to Ebert (S. of Eberth). In the next years many messages on a disease of L appeared. other animals. Spontaneous L. are described practically at all types house and a lab. animals; there are also single observations of L. at some wildings.
Soon behind the description of spontaneous L. animals messages on xenogenic and allogenic subinoculations of a disease appeared. Subinoculations of L., especially on singenny lines of mice, became one of widely used methods of experimental studying of L.
After discovery of chemical oncogenous substances and a role of ionizing radiation in emergence of malignant new growths experimental studying of L began., caused by chemical and beam factors. Virus L are intensively studied.
Pilot models for studying of L. are created on a lab. animals — mice. Researches are conducted also in the conditions of in vitro on the cultivated leukemic cells.
Spontaneous leukoses of animal, especially mammal all types, are the most adequate model L. person. They have the same morfologich. forms — leukemic and aleukemic, with a diffusion metaplasia and tumoral educations like lymphosarcomas, reticulosarcomas, myelosarcomas. In addition to similarity morfol, characteristics, it is revealed much in common in features of disturbance of metabolism and immunity though each species of animals has lines of quantitative indices of these disturbances.
The most numerous researches of spontaneous L. are carried out on mice. It is explained first of all by the fact that by inbreeding genetically pure lines of animals with high or low incidence are removed. AKR (60 — 80% of animals get sick), Afb (90% of females and 60% of males get sick), dba (35 — 40% of animals get sick), F (gets sick apprx. 50% of animals), etc. treat high-leukemic lines. C57BI, CC57BR, SZN, Swiss, etc. belong to low-leukemic lines. Division of lines of mice into high-leukemic and low-leukemic is based on percent of the animals who got sick by 12 months of life since by the end of life even at low leukemic lines (e.g., C57BI, CC57BR) about 15 — 40% of sick animals can be registered.
Artificial removal of high-leukemic and low-leukemic lines of mice which on many indicators are similar to high-cancer and low-cancer lines is one of proofs of the tumoral nature of L. Spontaneous L. and tumors of mice as model are convenient for studying of various questions of a pathogeny of a disease because the term of life of mice is small and allows to track in a short space of time all dynamics of development of pathology, to find out influence of these or those factors on the course of a disease. It is proved that decrease in caloric content of food, depletion of vitamin structure it considerably reduces incidence of L. and tumors; intercurrent diseases of animals, especially septic, also reduce the frequency of spontaneous L.
A great influence on development of L. render sex hormones. At the majority of animals, especially at mice, females are ill more often than males. Incidence of L. increases in that case when the little mouse is born from a young female of the high-leukemic line. As, according to a number of authors, estrogen is oncogenous substances, it was supposed that high incidence of females is caused by influence of female sex hormone. However experimental verification of this assumption yielded contradictory results: in one experiences the ovariektomiya reduced incidence of L., in others — did not exert any impact on its frequency. It is possible that sexual distinctions in a susceptibility to L. depend on the constraining effect of male sex hormones since long systematic introduction to females of androgens prevents spontaneous development of tumors. Considering that incidence of L. animals raises with age, it is possible to explain the increased incidence of females of bigger duration of their life.
Experimental data about bigger incidence of L. females of mice contradict about a wedge, observations since according to statistical data incidence of L. higher at men.
It is undoubted that the lack of corticosteroid hormones of adrenal glands influences development of L. After removal of adrenal glands animals get sick with spontaneous L more often.; administration of hormones of an adrenal gland or corticotropic hormone of a hypophysis, change of adrenal glands quite often prevent development of L. Numerous researches on animals accurately established therapeutic effect of use of adrenocorticotropic hormone and a cortisone at experimental L.
The leukoses caused by chemicals. Experimental L. can be caused in mice, rats, hens at influence of the chemical oncogenous substances approved concerning their ability to induce malignant tumors (1, 2, 5, 6-dibenzanthracene, 3, 4-benzpyrene, 20-metilkholantren, 9, 10 — — 11 1, 2 benzanthracene, 4 dimethylaminoazobenzene, orthoaminoazotoluene, nitrosamines, urethane). The dosage and ways of administration of these substances depend on their chemical structure and toxic action. For administration of these substances under skin, intramusculary or directly in the hemopoietic fabrics use oil solvents, during the greasing of skin — benzene, a xylol.
The most extensive and versatile researches are conducted on mice of different low-leukemic will deprive also not purebred mice.
At influence of chemical oncogenous substances the lymphoid leukosis, a myeloleukemia, a nondifferentiable form L develop., and also gematosarkoma (lymphosarcoma, reticulosarcoma, occasionally myeloma). In the same terms various malignant tumors on site of influence by oncogenous substances (sarcoma, a carcinoma cutaneum) or tumors of other bodies are found (gepatoma, adenocarcinomas of lungs, tumors of a stomach, a bladder both other malignant and benign tumors). Cases of simultaneous development of L are frequent. and tumors of various histogenesis.
It is possible to create special conditions for development in mice of L. by administration of oncogenous substances on easily soaking up solvents (e.g., on mouse fat).
L., caused by chemical substances, can be intertwined on other mice by intravenous, intraperitoneal, hypodermic administrations of blood, homogenates of marrow, spleen, limf, nodes of sick animals at observance of certain conditions (e.g., subinoculation on young mice of singenny lines, simultaneous influence with immunodepressants). Thus, by the subsequent passages it is possible to remove the intertwined experimental
L. L. strain, caused in animals by chemical oncogenous substances, are generally presented by the same types of spontaneous L. this line of mice, but they develop in earlier terms and in bigger percent of cases that confirms value of a genetic factor in development of L. animals. Development of these L. is defined also by such factors as a sex, age of animals, hormonal influences, food, vitamin balance, etc. At joint influence by chemical oncogenous substances and loadings B12 vitamin the percent of development of L increases. and tumors. These pilot studies will be coordinated with observations about an adverse current of L. at patients in whose blood and fabrics the content of B12 vitamin, its especially coenzymatical form — methylcobalamine is increased.
Emergence of L. at animals perhaps under the influence of the oncogenous substances which are formed in a human body (endogenous Oncogenous substances). Metabolites of heterocyclic amino acid of tryptophane and aromatic amino acid of tyrosine concern to them. L. M. Shabad established that introduction to mice of benzene extracts from a liver of the people who died from cancer causes development of tumors in animals. M. O. Raushenbakh, entering mice of low-leukemic lines benzene extracts from different fabrics and urine of sick L., observed development of L. and sarcomas at 54% of animals.
Metabolites of tryptophane and tyrosine are found in urine of patients with different forms L., and it is revealed that the greatest leykozogenny activity in an experiment those metabolites which with big constancy and in big concentration are excreted with urine of patients have. Specific mechanisms of education and accumulation in an organism of sick L are well studied. these endogenous oncogenous substances their mutagen action on the hemopoietic cells of mice and embryonic cells of the person is also established. Long introduction to mice of indole derivatives (an indole, indipan, 3-indolylacrylic to - that), aromatic derivatives of tryptophane (3 oxykynurenine, 3-oxyanthranilic to - that, beta aminoacetophenone), and also derivative tyrosine η-oxyphenyl-lactic to - you) causes development of L. and other tumors at 50 — 80% of animals.
Radiation leukoses. L., caused in animals by ionizing radiation, represent an important pilot model in connection with establishment of the fact of a direct connection between impact of various sources of ionizing radiation on the person and emergence of L. Izvestno at it about statistically reliable increase in incidence of L. among the population of Hiroshima and Nagasaki which underwent radiation as a result of explosions of atomic bombs.
Radiation L. can be induced at different types of animals (at mice, rats, Guinea pigs, dogs), however the greatest specific sensitivity to ionizing radiation mice have. L. also gamma radiations and way hron, influences of various radioisotopes are caused by single influence of sublethal doses of x-ray emission, y-radiation, bystry and slow (thermal) neutrons, and also fractional long influence x-ray (89Sr, 90Sr, 3PP, 134Ce, 140Ba, 198Au, 1:47).
Influence of external sources of radiation and some modifying factors on development of L is studied most in detail. at mice. Existence of direct dependence of frequency of development of L is shown. from the size of a dose of radiation at single or repeated exposition of animals. The size of a dose at the same time is various depending on the line of mice. Lymphoid leukoses develop more often and come to light earlier at a high dose of radiation, myeloleukemias develop at rather smaller dose of single exposition more often, but at hron, radiation come to light later on reaching high total doses. Setpoint value of an age factor: at radiation of newborn mice lymphoid leukoses usually develop; with age, in process of involution of goitrous gland, the frequency of lymphoid leukoses decreases, and myeloleukemias — increases. On development of radiation L. hormonal factors exert impact: removal of ovaries, administration of testosterone and a cortisone brakes or reduces development of L., removal of adrenal glands increases the frequency of development of lymphoid leukoses.
Removal of a spleen reduces the frequency of development of radiation myeloleukemias, and a thymectomy — goitrous lymphoid leukoses.
Leykomogenny action of ionizing radiation amplifies at simultaneous introduction to mice of oncogenous chemical substances.
During the studying of radiation L. dogs it is established that development of a disease is preceded by the period of oppression of a hemopoiesis. These experimental data are according to a wedge, observations of the hypoplastic conditions of a hemopoiesis preceding development of L. person.
Radiation L., caused by administration of radioisotopes, are described generally at rats, but there are separate messages on induction of L. at mice, rabbits and dogs. Along with L. bone tumors (sarcomas) often were found in animals under these conditions.
Transplant leukoses. One of important models of experimental L. the transplant L is., developing at subinoculations of the spontaneous or induced by chemical and beam factors L. Subinoculations are carried out on singenny lines animal by hypodermic, intraperitoneal, intravascular administrations of blood, suspension of marrow, spleen, limf, the nodes, a thymus gland received from leukemic animals. Initial subinoculations are successful on newborn animals better. By repeated subinoculations it is possible to create a strain of the intertwined L. from 100% result development of a disease. Model of transplant L. allows to receive significant amounts of leukemic cells for cultivation of in vitro, for studying biochemical, features, for cytochemical, and cytogenetic analyses, for immunol, researches, for studying of questions of a tumoral progression. Models of transplant L have special value. for experimental therapy. This or that strain of the intertwined L. use depending on problems of tests of antileukemic efficiency of chemotherapeutic drugs. For the solution of some questions of experimental therapy of L. sometimes use model of spontaneous L. domestic animals, preferential dogs.
Due to the removal of breed of bestimusny mice with a reduced immune response on graft-specific antigens there were attempts to use these animals for change of tumors of the person with the subsequent tests of chemotherapeutic drugs. However these attempts did not come true since successfully vaccinated tumors quite often are exposed to spontaneous regression. For experimental therapy various virus L can be used. mice, easily reproduced and standardized on type L., to terms and percent of development of a disease.
By comparison of various models of experimental L. the common features characteristic of L come to light. animals. Irrespective of a way of reproduction at the developed picture of a disease patomorfol., patofiziol, and gematol, indicators at all animal species are same and differ only according to gistogenetichesky option L. The diagnosis is based on a careful patogistol. the analysis of systemacity of defeat, and at tumoral options — on tsitol, the analysis of fabric of a tumor.
For establishment of type L., in addition to tsitol, characteristics of blast cells, shall be applied cytochemical, reactions.
At mice leukemoid tests on different infections and toxic factors presenting sometimes the known difficulties for their differentiation from true L quite often develop. Absolute criterion of true L. test, i.e. ability to be intertwined on singenny lines animal is positive biol.
Viral leukoses. Virus etiology of L. birds and mammals it was established in 1908 — 1909 by the Danish researchers Ellermann and Bang (V. E Hermann, O. to Bang) who caused a disease in healthy chickens by introduction of nanometer of acellular extracts of leukemic cells of chicken.
There is a point of view that etiol, a factor of L. viruses are, and other factors are considered as cofactors.
Experimental virus L. are the main models for studying of properties of oncogenous RNA-containing of viruses, the mechanism of the transforming action of a virus on a cell, problems of epidemiology of viral diseases.
Experimental virus L are described. hens and bird species close to them, and also mice, rats, hamsters, Guinea pigs, rabbits, cats, cattle and primacies. Experimental virus L are most studied. birds, mice, cats and cattle. Etiol, agents at all types are RNA-containing Oncogenous viruses (see), on the morphology belonging to S-type of viruses.
Viruses L. hens are called by various forms L. birds. Myeloid a neoplasia of hens are divided into two types — the myeloblastosis which is characterized by enormous number of leukemic myeloblasts in a blood channel (till 1010 in 1 mkl), and miyelotsitomatoz — generally aleukemic form with focal proliferation of myelocytes. The virus of a myeloblastosis (a laboratory strain of BAI — And), in addition to a characteristic myeloblastosis, causes in chickens also sarcomas, an osteoperosis, a lymphomatosis and nefroblastoma; unlike all other viruses L. birds, it causes still carcinomas, a chondroma and ossiform damages of kidneys.
From the viruses causing miyelotsitomatoz the strain of MS-29 which has a wide range of tumoral transformation of cells of chickens is most studied, causing osteochondrosarcomas, an osteoperosis, endotheliomas, mesotheliomas, a myeloblastosis, a lymphomatosis, adenocarcinomas of kidneys, adenomas and carcinomas of a liver. In vitro MS-29 causes very bystry (in 24 hours) and nearly 100% transformation of cells of embryonal tissue of chickens. A target cell for both called strains same — an ekstrasinusoidalny hemocytoblust.
The virus of an eritroblastoz, in addition to an eritroblastoz, causes in sensitive chickens a lymphomatosis, sarcomas, an osteoperosis, occasionally adenocarcinomas of kidneys. In vivo a target cell of the transforming action of a virus of an eritroblastoz — an intrasinusoidalny hemocytoblust. At the developed stage of a disease the infected cells are not differentiated further a stage of an erythroblast. The strain of R causes in vitro transformation of embryonal fibroblasts of chickens.
Sensitivity of chickens to oncogenous action of viruses of a myeloblastosis and eritroblastoz depends on a genotype of the line and age. At the same time 3-day chickens are most sensitive to a virus of a myeloblastosis. For a virus of an eritroblastoz dependence of sensitivity of hens to oncogenous action is inversely proportional to age. All these viruses represent the mixed heterogeneous populations consisting of the virus causing a basic disease, and the viruses which are not transforming, but closely associated with them, on morphology and antigenic properties not distinguishable from the transforming agent. These viruses received the name of «viruses assistants» and also were the heterogeneous population containing both pathogenic, and nonpathogenic forms.
The visceral lymphomatosis is characterized by primary localization of tumor lymphomatous cells in a bursa of Fabricius and the subsequent their migration and infiltration of parenchymatous bodies, hl. obr. liver, spleen and ovaries. The virus of a visceral lymphomatosis is rather eurysynusic in populations of hens of poultry-farming farms of the different countries. The main form of a carriage of a virus — an asymptomatic infection. The infected hens can transmit a virus horizontally (a source of a virus — kcal, a discharge of a nasopharynx); at the same time the infected birds get sick seldom, the most frequent result of such infection — durable immunity to a virus. The virus of a visceral lymphomatosis can be transmitted and vertically — from mothers to posterity, and at the infected embryo the expressed viremiya is noted. The hatched chickens are tolerant to a virus and are one of the main sources of a horizontal infection; the lymphoid leukosis can develop in the late periods of life at such chickens.
The bursa of Fabricius is so-called key body for development of a visceral lymphoid leukosis: removal it within the first 3 months of life practically excluded a disease at neonatalno the infected birds. Later of Ektomiya's bursas (5 months) is less effective. The thymectomy had no significant effect on development of a lymphoid leukosis of hens.
Leukemic viruses of hens depending on properties of an outer membrane are divided into five subgroups — A, B, C, D and E, each of which has the individual standard antigen corresponding to a range of lines of hens and embryonic cells of chickens the, sensitive to this type of a virus, determined by in vitro. It is connected with the fact that to each subgroup there corresponds a certain cellular receptor (And, In, With, Du E). During the loss by a cell of a receptor it loses sensitivity to the corresponding virus.
Four loci — tva, tvb, tvc and t ve controlling sensitivity of cells to viruses of subgroups And, In, by C and E respectively are described. Experiments on crossing of hens with phenotypes, different in sensitivity, show that genetic loci of tva and tvb are inherited independently from each other and perhaps are even localized in different chromosomes, loci of tva and tvc are connected among themselves. For tvb two alleles of sensitivity are described, one of them is associated with antigen of erythrocytes. Sensitivity of cells to viruses of subgroup of E (endogenous viruses) is defined by two or three not linked genes.
The described division of leukemic viruses of birds into five subgroups depending on type of a cellular receptor completely matches with immunol. specificity of the main antigen of an outer membrane of viruses of these subgroups (in a neutralization test).
Viruses of group of a reticuloendotheliosis of birds combine a virus of a reticuloendotheliosis of birds, a virus of a necrosis of a spleen, a virus inf. anemias of ducks and sintsitiyobrazuyushchy virus of chickens. The virus of a reticuloendotheliosis of birds causes a characteristic reticuloendotheliosis in chickens, quails, ducklings, gooses, turkeys, pheasants, etc. Main «target» of the transforming action of a virus — a cell of marrow.
Virions of this group of oncornaviruses contain 60 — 70 S RNA and enzymes of a complex of the return transcriptase, however the homology between RNA of viruses of group of a reticuloendotheliosis and viruses of a leukosis of hens is absent. Viruses of group of a reticuloendotheliosis do not interfere in culture of fabric with these viruses, cannot serve as viruses assistants for defective strains and leukemic viruses and, therefore, have no general with them cellular receptors. Studying of cross-neutralization also did not reveal the general antigens in an outer membrane of virions of both groups of viruses. Complementation, phenotypical mixing or a recombination between viruses of these two groups is not revealed; gs - an anti-gene — the general for all viruses L. hens, it was not found in viruses of group of a reticuloendotheliosis. The return transcriptase of viruses of this group has antigenic looking alike enzyme of viruses L. mice.
Other widespread model of experimental virus L. L are. mice. It is established that approximately 80 — 90% of mice of the AKR line on 8 — have spontaneous T-cellular timuszavisimy lymphoid leukoses 11th month. In 1950 — 1951 L. Gross showed that introduction of acellular filtrates of leukemic tissues of such mice to newborn little mice leads low-leu-koznykh of lines to development of a lymphoid leukosis in them.
At serial passages of the leukemic virus allocated with L. Gross on newborn mice of the C3H line the high-pathogenic option — Gross A. virus was received. The virus was vysokopatogenen for mice and rats and often caused a lymphoid leukosis with short stage of latency.
The etiology and a pathogeny of a so-called spontaneous lymphoid leukosis of mice of the AKR line are represented as follows: in a genome of all cells of mice of the AKR line genomes of the endogenous ekotropny mouse AKV-1 and AKV-2 viruses are integrated. These genomes express from the first days of post-natal life and in bodies, and tissues of mice of the AKR line (especially in a spleen); constantly, throughout all life of an animal characteristic particles of S-type of an ekotropny virus are found. However in spite of the fact that AKV-1 and AKV - 2-virus particles of an infektsionna in culture of fabric are also found in a high caption in young mice of the AKI line, they are not leykomogenna. Approximately on the 6th month in a thymus gland of mice of AKR one more endogenous virus — ksenotropny which in itself is not leykomogenny or pathogenic too begins to express. However in the course of an expression of a ksenotropny virus in a thymus gland there are recombinant MCF forms of this virus with an ekotropny endogenous virus. MCF hybrid forms also possess direct leykozogenny action, causing development of a spontaneous lymphoid leukosis of mice of the AKR line. However only the expression of an endogenous and ksenotropny virus still is not enough for formation of a recombinant form and developing of a disease. Not less important role belongs to a genotype and the fabric of a thymus gland — fabric of a target of the transforming action of a recombinant form.
Mice of the C57BL line belong to group of low-leukemic lines, the frequency of spontaneous L. at which it is extremely low, and the disease comes to light only at old animals. However R-radiation of young mice of this line it is possible to cause them in 80% a lymphoid leukosis, at Krom extracts of tumoral fabric contain the virus particles of S-type (RadLV) having leykomogenny activity and being etiol, the agent of radiation L. mice of this line. Idiosyncrasy of RadLV should be considered that only cells of one type of a differentiation — lymphoblasts of a thymus gland of mice permissive system for its replication. It is not excluded, as it is a recombinant of two endogenous viruses, one of which ekotropny, another — ksenotropny.
A. Graffi and sotr., apparently, were the first who made systematic attempts to allocate the virus agent from intertwined by cells well-known a lab. strains of tumors of mice. These experiences resulted in result, unexpected for authors: inokulirovanny mice had leukemias instead of estimated solid tumors.
The virus allocated to Graffi caused in the line of mice, to-ruyu authors, myeloid leukemias, including chlorine used leukemia. However at introduction of a virus to mice of other lines also other forms of leukoses — a lymphoid leukosis, blast forms were received. The virus of Graffi was transmitted with milk. The virus of Graffi caused lymphatic leukemias and lymphosarcomas in rats.
From sarcoma 37, a lab. a strain of a spontaneous adenocarcinoma of a mammary gland the virus of Moloni which is browned on mice of different lines is allocated. The virus of a leukosis of Moloni causes the disseminated lymphosarcomas or generalized lymphatic leukemias in mice of the most different lines. After serial passages pathogenicity of a virus sharply increased, and it began to cause leukemias and at introduction to his adult mice. Moloni's virus patogenen for rats, causing in them a lymphosarcoma of a thymus gland, and for hamsters in whom causes reticulosarcomas.
Acellular extracts of a carcinoma of Ehrlich at introduction to their newborn mice the Swiss lines caused significant increase in a spleen in experimental animals. This spleen was also a source for allocation of a new leykomogenny virus — a virus of the Friend. At introduction to newborn and adult mice of a number of lines it causes a characteristic leukemic syndrome — increase in a liver and spleen with the expressed changes of peripheral blood. The disease is described as erythroleukaemia or Eritroblastoz.
From astsitny option of a lymphoblastoma of Shvartts — Skulmen the virus which at introduction to mice suckers of the BALB line caused in them increase in a spleen and limf, nodes is allocated. After browning on young mice of the BALB line pathogenicity of a virus sharply increased, and thus one more nowadays well-known and widely used virus strain of an experimental leukosis — Rausher's virus was received. Rausher's virus causes a disease in adult mice of sensitive lines, on macro - and a microscopic picture not distinguishable from the eritroblastoz induced by a virus of the Friend. Viruses of the Friend and Rausher cause lymphatic leukemias in rats.
The subsequent studying of both of these viruses showed that populations of their geterogenna and contain two types of virus particles: one — defective, causing tumoral transformation of gematopoetichesky cells, on not capable to breed without virus assistant, others — - the bearing functions of a virus assistant. The last represent the viruses of type of Gross causing lymphoid leukoses in mice and rats or the viruses causing myeloid leukemia of mice.
The virus of a leukosis of Kirshtayn is isolated from a spontaneous lymphoma of a thymus gland of old mice of the SZN line. The damages caused by this virus are similar to a disease at a leukosis of Rausher and Friend; at the survived mice in 4 — 9 months lymphoma of a thymus gland develop.
The virus of a leukosis of Abelson is allocated from the mice of the BALB line infected with Moloni's virus. It causes at introduction to newborn mice of a lymphoma of B-type. The virus can be replicated in cellular cultures and is capable to cause morfol, transformation of lymphoid cells of in the vitro B-type. The component responsible for transformation of lymphoid cells is defective and demands a virus assistant for the replication.
At infection of mice of the CC57BR line with standard drugs of a live smallpox vaccine they had an acute L. The subsequent studying showed that L. resulted from activation of a latent leukemic virus of mice of the GG57BR line (Mazurenko's virus). This virus managed to be allocated from leukemic tissues and bodies of sick animals and to cause with its help an identical disease in newborn mice. On the immunol, properties Mazurenko's virus is close to viruses L. mice of Rausher, Moloni and Friend.
In addition to these most studied leukemic viruses, also other viruses allocated from various intertwined tumors of mice are described: it is Frenks's virus — from sarcoma 37, Stensli's virus — from Ehrlich's carcinoma, Stepina's virus — Zilbera — from the intertwined tumor of a mammary gland of mice of the SZNA line.
Virus L. cats (FeLV) is etiol, the agent of lymphoid leukemia of domestic cats; in a lab. conditions caused a lymphoid leukosis in cats and dogs. It is not excluded that the FeLV virus — etiol, the agent and other diseases of cats — myeloproliferative defeats, inf. peritonitis, atrophy of a thymus gland, fibromas and some anemias. The FeLV virus well breeds in the cellular cultures received from cats and other animal species without causing in them any visible changes. In an organism the main breeding ground and, perhaps, a target of the transforming action — lymphoid cells of marrow.
All allocated strains of viruses L. cats had the general gs-antigen, but differed on antigens of an outer membrane. On this sign they were divided into subgroups And, In and Page. Viruses of subgroup And usually meet in the form of monoinfection while viruses of subgroups In and With often meet in the form of multi-infection (And + In, And + With or And + In + C). The type B, unlike other types FeLV, in vitro has a wide range of sensory cells of the person and various animals for a productive infection.
The FeLV virus is eurysynusic in population of domestic cats; more than antibodies to virionny and virusindutsirovanny FeLV antigens were found in 40% of healthy animals. At the same time the frequency of spontaneous developing of leukemia at cats does not exceed 0,05%, perhaps, in connection with a high seropositive background of population. The virus is transmitted horizontally, the main source of a virus, apparently, saliva and urine of the infected animals. Induction of L. at a horizontal infection of both kittens, and mature animals it was confirmed experimentally. Antibodies from the infected mothers are transferred to posterity, a cut gains resistance to oncogenous action.
From leukemic cells of sick animals characteristic particles of S-type which are carried to viruses L are allocated. cattle; frequency of allocation of such particles increased during the processing of cells phytohemagglutinin. In serums of sick animals in 90% of cases antibodies to antigens of virus particles are found. It was not succeeded to find any general antigens in particles of S-type from leukemic cells of cows with other types and groups of S-type of oncornaviruses of mammals. Much more rare and in a smaller caption of an antibody are found also in healthy cows. At the same time direct dependence between the frequency of cases of L is noted. in this herd and number of healthy animals in whom antibodies to a virus are found. Antibodies to a virus also, apparently, as well as a virus, can be transmitted through milk. The particles of S-type allocated from leukemic cells of cattle caused lymphoid leukoses in calfs and a lymphosarcoma at sheep at introduction by their newborn animal.
In 1972 from a gibbon of a type of Hylobates LAK with a spontaneous lymphosarcoma the oncornavirus of S-type (GaLV) which at introduction to newborn gibbons caused in them acute lymphoblastic leukemia or the disease reminding hron, myeloid leukemia of the person was allocated. There are already several relatives among themselves of the GaLV isolates emitted from sick and healthy gibbons.
The virus is transmitted horizontally; in serums of monkeys of certain colonies are available Antitela to it.
The GaLV virus antigenically and on properties is similar to the SiSV virus allocated from a spontaneous fibrosarcoma of woolly monkeys of the New World. At experimental introduction the SiSV virus causes sarcomas and fibrosarcomas in several species of monkeys. The SiSV virus is defective, transforming fibroblasts; the helper is necessary for its replication. Such assistant is the GaLV virus or any other, similar to it. There are bases to consider that SiSV — GaLV viruses came from endogenous viruses of S-type of some species of Asian mice.
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A. I. Vorobyov, A. N. Smirnov; Yu. Ya. Ashmarin (dermas.), L. A. Makhonova (ped.), AA. 3. Novikova (rents.), I. A. Iyereslegik, E. M. Filkova (I am glad.), M. O. Raushenbakh (experimental leukoses), M. P. Khokhlova (stalemate. An.).