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Immunotherapy - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Remission and recurrence of an acute leukosis
Inborn leukosis
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

The modern chemotherapy of acute leukoses, despite considerable lengthening of life of patients, did not solve a problem of full treatment. Only in a small number of cases of an acute lymphoblastoid leukosis (5%) it is about possible recovery. It speaks about limitation of chemotherapeutic influence and forces to conduct searches of new ways of therapy of acute leukoses. One of the directions in modern hematology is development of immunotherapeutic methods of treatment. Understand such impact on an organism of patients which leads to mobilization of immune forces and development of specific anti-leukemic immunity as an immunotherapy.
The foundation of an immunotherapy was laid by detection of specific leukemic antigens. Their existence testified to a possibility of an immune response of an organism on this irritant and consequently, about development of anti-leukemic immunity. Cases of spontaneous remissions, known in clinical practice, at leukoses with a high probability can be explained with immunologic mechanisms.
The data obtained in recent years authentically indicate high performance of the immunotherapy allowing at an acute leukosis at children to prolong remission by 2 — 3 times. Immunotherapeutic influence has a number of advantages in comparison with chemotherapy. One of them — specificity of action on tumor cells without damage of normal fabrics and bodies. However the immunotherapy cannot be considered as the main complex in treatment of acute leukoses. It first of all is caused by the fact that the leukemic agent possesses weak antigenicity and consequently, the immunological answer of an organism will also be weak. Therefore now the immunotherapy is considered as the means supplementing the main cytostatic therapy. The isolated use of immune drugs for induction of remission is ineffective in connection with weak anti-leukemic activity. From modern positions the most optimal and perspective variant is the combined himioimmunoterapiya which is carried out to the remission period. At reduction of tumoral mass of cells to 105 (it is reached by cytostatic drugs during induction) immune systems of an organism can take under control and complete destruction of the remained not proliferating leukemic pool (J. P. Levy, 1973). Value of an immunotherapy during remission is defined by one more important point. The number of remissions at an acute leukosis at children is rather high. However against the supporting cytostatic therapy at many patients the infectious complications which are quite often leading to a lethal outcome develop. The immunotherapy softens an immunodepressive effect of himiopreparat, stimulates an organism immunoreactivity. Immunological inspections of the children sick with an acute leukosis who received an immunotherapy by various methods demonstrate the considerable stimulating effect of both humoral, and cellular links of immunity. Though the effect first of all consists in increase of level of immunoglobulins, i.e. in stimulation of mainly humoral immunity.
Now in an immunotherapy several directions depending on specificity and a way of impact on an organism are allocated. Distinguish an immunotherapy passive specific, adaptive specific and nespstsifichssky, active specific and nonspecific.
The passive specific immunotherapy assumes introduction by the patient of immunological factors by use of allogenic and heterogeneous serums. The passive immunotherapy did not find broad application. On the one hand, it has insignificant therapeutic effect, with another — cases of progressing of tumoral growth are noted. Therefore development of a passive immunotherapy remains at the experimental level.
Adaptive (from armor. adopter — to adopt) the immunotherapy consists in introduction to an organism of the patient of immune cells — lymphocytes for their engraftment and receiving an immune response. If enter lymphocytes from healthy neimmunizirovanny donors, such therapy is nonspecific and if from immunizirovanny donors or donors - convalescents — therapy has character of adaptive specific. According to researchers, the adaptive immunotherapy is a perspective method of impact on tumoral process. However now the majority of data has experimental character. Clinical supervision on use of an adaptive immunotherapy, despite the encouraging results, are still not numerous and inconsistent. The most powerful clinical results are received at use of an active immunotherapy. The active specific immunotherapy assumes a specific immune response of an organism on administration of leukemic antigens (vaccines). The active specific immunotherapy is carried out, using various vaccinal material, in particular living leukemic cells (S. V. Skurkovich, N. S. Kislyak and soavt., 1969) which can stimulate both humoral, and cellular immunity. Also the tumor cells processed by radiation or formalin are applied (G. Mathe, 1971). However they possess smaller immunological activity though are at the same time less dangerous to reinfection of leukemic process in comparison with living tumor cells. At active specific immunization as material both own cells (autologous), and the cells taken from other patient (allogenic) can serve. And many researchers note that autologous cells differ in weak immune impact on the owner's organism. The much bigger immune response should be expected from allogenic leukemic cells. However in practical activities use of an active specific immunotherapy is limited a number of factors, first of all, to impossibility of creation of bank of leukemic cells at all children's hematology units. Besides, active specific immunization is limited to the fact that as vaccinal material apply cellular substrate, but not pure specific leukemic antigen. It causes side allergic reactions and reduces therapeutic effect.
From these positions the most acceptable for wide use is the method of active nonspecific immunization. This method provides stimulation of all immune mechanisms, including mechanisms of antineoplastic protection. It is reached by introduction of nonspecific immunostimulators. Such nonspecific stimulators are various vaccines, microbic drugs, synthetic adjuvants: BTsZh, levamisole, pertussoid vaccine, interferon, phytohemagglutinin, etc. The active nonspecific immunotherapy causes stimulation of cellular and humoral mechanisms of immunity, including the links specific concerning leukemic cells. Broad application in clinical practice was found by BTsZh vaccine. It is an immunostimulator with the multistage mechanism of action which is consistently including specific and nonspecific defense reactions. For the last decade the considerable material testimonial of efficiency of an immunotherapy at an acute leukosis at children by BTsZh vaccine during remission in combination with himiopreparata is saved up. So, the average duration of remission and life increased almost twice in comparison with that at the children receiving only chemotherapy. Therefore, the combined active nonspecific immunotherapy during remission at observance of the general rules of treatment promotes considerable lengthening of life of sick children. Technical simplicity and clinical performance do an immunotherapy by a vaccine of BTsZh acceptable for wide practical use.

Fig. 12. Scheme of an immunotherapy vaccine of BTsZh of the children sick with an acute leukosis (N. S. Kislyak, 1978)

In this regard we provide the scheme and equipment of an immunotherapy BTsZh vaccine applied in our country (N. S. Kislyak, V. M. Bergolts, V. S. Yeremeyev, 1978) (fig. 12).
For immunization use the dry lyophilized BTsZh vaccine. Active nonspecific immunization is carried out to the period of full kliniko-hematologic remission against the supporting chemotherapy. The immunotherapy is carried out by a course method by weekly intradermal vaccination on 0,1 mg of drug throughout 5 —
6 months (20 injections) with 5 — a 6-month interval. The single dose (0,2 ml) is received at cultivation of a dry vaccine in 2 ml of isotonic solution of sodium of chloride.
The vaccine is prepared just before the use and entered strictly vnutrikozhno. The course dose makes 2 mg of a dry vaccine of BTsZh. During an immunotherapy course BTsZh vaccine at children notes local and general reactions. Local reactions are similar to that at vaccination and a revaccination at healthy children. In the place of an injection in the first days the limited inflammation is noted. In 4 — 6 weeks after vaccination immunity develops, formation of a papule, pustule with a crust or an ulceration is possible further. Local vaccinal reaction comes to an end with scarring. Gradually, with increase of number of vaccination, the course of local reactions changes. There is no early inflammatory reaction and the current of infiltrative, papular, pustular phases and process of scarring accelerates. Except local, the general reactions can occur at a number of children. Most often there is a temperature increase to subfebrile against a febricula. Also there is a reaction of peripheral lymph nodes. As a rule, the lymph nodes, next to the place of an inoculation, are involved — insignificant increase and consolidation is noted them, but they are painless. Such general reactions do not demand treatment and are not contraindication for continuation of an immunotherapy. Now researches on allocation of the operating BTsZh vaccine component draw attention. Such immunogene component is MER which in experiment strengthens development of both humoral antibodys, and cellular immune responses. There were messages and on clinical performance of MER at treatment of an acute leukosis.
For the purpose of active nonspecific therapy, except use of mycobacteria and their fractions, attempts to use other microorganisms become, in particular were investigated parotitis and pertussoid
vaccines. They were less effective, than BTsZh vaccine. The encouraging results were received when using as immunoadjuvant of the drug "Korinebakterium Parvum".
This drug contains suspension of covers of bacteria saprophytes of skin of the person, has the expressed stimulating effect which is followed by increase of level of immunoglobulins. The clinical assessment "Korinebakterium parvum" at treatment of an acute leukosis at children, carried out in the Soviet Union, testifies to its efficiency (A. G. Rumyantsev, N. S. Kislyak, 1980). Use of a himioimmunoterapiya during remission showed reliable increase in duration of remission. The drug "Korinebakterium Parvum" also gives local and general reactions — morbidity in the place of an injection, temperature increase, increase and consolidation of regional lymph nodes. Unlike BTsZh vaccine, at the same time there is no danger of dissimination of a vaccine.
The combined himioimmunoterapiya is the perspective direction in development of remedies for acute leukoses.

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