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Myelosis - 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
Immunotherapy
Remission and recurrence of an acute leukosis
Inborn leukosis
Neuroleukosis
Myelosis
Lymphogranulomatosis
Gematosarkoma
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Leukopenias
Histiocytoses
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Angiopathies
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
Coagulopathies
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Angiohemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Dysfibrinogenemias
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
Thrombocytopenia
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
Trobotsitopatiya
Anemias
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 myelosis is the tumoral disease of the hemopoietic system arising from a myeloid sprout of a hemopoiesis. The main pathological substrate of a tumor is made by granulocytes, mainly mature forms. The tumoral progression at a myelosis has two stages. The first stage — developed, high-quality, characterized by a tumor monoklonovost, the second — malignant, caused by development of new quality of tumor cells — poliklonovost (A. I. Vorobyov, 1979).
The myelosis at children's age meets seldom. According to various authors, he is marked out in 2 — 5% vsskh leukosis cases at children. The myelosis is the only tumoral process at which there are accurate chromosomal disturbances — defect of the 22nd couple (Philadelphian Ph' - a chromosome). Existence of Ph '-chromosomes is considered a pathognomonic sign of a myelosis. As a result of long-term cytogenetic researches two groups of diseases are allocated: myelosis option with Ph' - a chromosome (Ph '-positive) and option at which by Ph' - the chromosome is not defined (Ph '-negative). Feature of a children's form of a myelosis is lack of a Philadelphian chromosome. At a myelosis Ph' - negative forms occur at adults. Lack of Ph '-chromosomes regard as an adverse sign when determining the forecast. The disease proceeds heavier, average duration is less, than at patients with Ph' - a positive form.
The myelosis at children's age has features of a clinical current. At children allocate 2 options of a disease. The adult (adult — mature) type does not differ on a current from that at senior citizens. The juvenile type of which lack of Ph '-chromosomes is characteristic has a number of kliniko-hematologic features. The basic is more acute heavy current and low average life expectancy. The adult type of a myelosis, as a rule, occurs at children of advanced age. The juvenile type is observed at younger age — till 3 — 5. However the age is not fundamental in development of a certain form at early children's age. Some researchers, proceeding from features of a current of a juvenile form, at emergence of process in the first years of life assume inborn character of a myelosis.
In a clinical current of a myelosis allocate several stages. An initial stage which can proceed asymptomatically with insignificant hematologic signs the leukocytosis and shift of a formula are first of which to the left. I. A. Kassirsky and G. A. Alekseev (1970) consider necessary to allocate the preleukemic period. The specified authors on the basis of a retrospective assessment refer small neutrophylic shift and a hyperglobulia to signs of the preleukemic period. However identification at children of neutrophylic shift should not be regarded as manifestation of a myelosis at all. In pediatric practice tens of states which are followed neutrophylic reactions are known. Therefore each case demands the careful clinical analysis.
The initial stage of a myelosis can not give a long time of manifest signs. The disease develops gradually, against the general wellbeing and in many cases is diagnosed in the developed illness stage. The general condition of patients worsens, the spleen increases, characteristic changes in peripheral blood appear. At modern therapy the developed stage of an illness can proceed several years. The long current is characteristic of adult type, at a juvenile form process develops violently, within several months. At a certain stage process passes into an end-stage when klinikogematologichesky symptoms quickly progress, anemia, thrombocytopenia accrue and the hematologic picture of an illness changes — there is a blast transformation of a marrowy hemopoiesis (blast crisis). The terminal period arises in steps, it is difficult to predict its development. And blast crisis is observed equally often as at treated, and uncured patients though at the last it develops earlier.
During a myelosis of adult type all stages of an illness are traced: an initial stage, the developed stage, the terminal period.
In an initial stage the general state is broken a little. Children keep activity, feel well. As a rule, do not complain of anything though weakness and fatigue can periodically be noted. At most of children appetite is kept, at some anorexia is possible. There are no pallor of integuments, a hemorrhagic syndrome, a hyperplasia of bodies. But the spleen (it is palpated 1 — 2 cm below than a costal arch, painless, soft) and a liver can be slightly increased. In general the clinical picture of a myelosis in an initial stage is very poor that complicates early diagnosis. Therefore crucial importance at detection of a disease has research of peripheral blood. At all patients the neutrophylic leukocytosis within 20 — 50 X 109/l with shift to the left to myelocytes and promyelocytes is observed various degree. Morphologically granulocytes have no strong indications of an anaplaziya and do not differ from those at healthy children. Content in blood of an alkaline phosphatase is a differential sign with leukemoid tests of myeloid type. Already in an initial stage of a myelosis concentration of an alkaline phosphatase of neutrocytes in peripheral blood is sharply reduced. In a leykogramma the quantity of eosinophilic and basphilic granulocytes (eosinophilic and basphilic association) can increase that is an important symptom of a myelosis. In peripheral blood the quantity of erythrocytes and hemoglobin remains normal. Within normal amounts SOE remains, less often it increases. The quantity of thrombocytes are normal more often, the insignificant thrombocytosis within 500 — 600ò109/l can be observed. In an initial stage there are minor changes of marrowy punctate. At the kept sprouts of a blood formation and the normal maintenance of blast cells promiyelotsitarno-myeloid reaction, the raised index of maturing of granulocytes are noted. Duration of an initial stage of a disease can fluctuate from several months to several years, but 6 — 12 months are most often limited.
The period of the developed kliniko-hematologic picture of a myelosis is characterized by increase of the symptoms caused by generalization of tumoral process. The condition of patients considerably worsens that is caused by intoxication and defeat of a nervous system. The behavior of the child changes, children complain of weakness, slackness, fast fatigue, appetite decreases, loss in body weight is noted. Most of children has subfebrile temperature, sometimes a hyperthermia.
Emotional lability, decrease in working capacity, bad dream, headache, perspiration are noted. The progressing increase in a spleen connected with proliferation of tumor cells in this body belongs to characteristic signs of the developed stage. The spleen increases to the huge sizes. In some cases it is palpated at an entrance to a small pelvis. At a palpation find considerable "stony" density. As a result of a splenomegaly the stomach is increased in sizes. Periodically there is an abdominal pain caused by stretching of a capsule of a spleen and a prelum of internals. In some cases the syndrome of an acute abdomen is connected with developing of heart attacks of a spleen. In a stage of a heat the hepatomegalia which most often is moderately expressed is noted. Liver sizes much less, than spleen sizes. The hyperplasia of lymph nodes, a hemorrhagic syndrome are less often observed. More typical sign is the ostealgia. Ossalgiya can be combined with an arthralgia. At children damage of skin in the form of allergic rash is possible. In the period of the developed stage of a myelosis the hematologic picture changes. The leukocytosis accrues, reaching level 100 — 200 X 109/l and more. In a leykogramma all cellular forms of a myeloid row meet: from myeloblasts to band neutrocytes. Myeloblasts come to light in insignificant quantity (1 — 5%) at the increased maintenance of promnelotsit. The expressed lymphocytopenia is usually noted. In comparison with an initial stage more century of a yrazhen a basophilia with simultaneous, but to a lesser extent, increase in quantity of eosinophilic granulocytes. In process of a course of a disease normokhromny anemia accrues. SOE increases. The quantity of thrombocytes usually remains in normal limits. Research of marrow has no crucial importance as changes not of a patognomonichna for a myelosis. Rejuvenation in a granulotsitarny sprout is not noted, the maintenance of blast cells increases slightly. Marrow is rich with cellular elements, granulocytes prevail. The leukocytic and erythroidal ratio increases, making 10: 1 and more. It is not result of oppression of a red sprout and is explained by the expressed hyperplasia of a granulotsitarny sprout. Though in the developed myelosis stage the reduction of an erythroidal sprout of a hemopoiesis is already noted. Duration of the period of the developed klinikogematologichesky picture fluctuates within 3 — 5 and more. Natural manifestation of a tumoral progression is transition of leukemic process to an end-stage. As A. I. Vorobyov (1979) notes, in this stage the malignant properties of a tumor defining weight of a clinical picture and resistance to therapy are shown. The terminal period, in particular blast crisis, on klinikogematologichesky symptomatology differs from the developed illness stage. As a rule, blast crisis develops suddenly against the carried-out therapy. In many cases it is difficult to predict approach of blast crisis. To early harbingers of the terminal period the accruing leukocytosis and the increase in a spleen testimonial of development of resistance belong to therapy (Myelosanum). In this stage the condition of children sharply worsens at the expense of the accruing intoxication. Pallor of integuments, a hyperthermia is expressed. Progressive loss in body weight up to a full cachexia is noted. Lymph nodes are involved in pathological process. Increase is observed in all groups, nodes dense, painless. A frequent symptom of the terminal period of a myelosis is the painful ostealgia. Necrotic damages of skin and mucous membranes of an oral cavity, education on skin of leukemic infiltrates are characteristic (leukemids). One of the leading clinical signs is the hemorrhagic syndrome, heavy nasal, gastrointestinal bleedings, hematencephalons are possible. As a result of intoxication are noted weakness of cardiovascular activity, arrhythmia, borders of heart are expanded, tones deaf. The spleen and a liver remain the former sizes or can increase even more, despite therapy. Gepatosplenomegaliya is followed by an acute pain in a stomach.
In recent years the myelosis in an end-stage often is followed by specific leukemic defeat of the central nervous system that is explained with increase in life expectancy of patients. Clinical displays of a neuroleukosis at a myelosis are also various, as well as at an acute leukosis. Signs of defeat of covers of a brain, brain substance, the mixed option are noted. To Tsitomorfologicheski cells of cerebrospinal fluid are identical to cells of peripheral blood and marrow that testifies to           metastatic nature of defeat of a nervous system.
The leading hematologic sign of an end-stage is blast crisis which is characterized by increase in blast cells in peripheral blood (more than 10%) and marrow (more than 20%). In some cases the myelosis at children for all years of a current is followed to constants blastozy (10 — 15%) in peripheral blood. However marrow remains polymorphic on cellular structure, there are no signs of the terminal period that allows to regard blastoz as manifestation of the developed stage, but not blast crisis. Cellular substrate of a tumor in period.blastny crisis convincingly shows a poliklonovost of malignant process in this stage. Morphologically and tsitokhimichesk are defined various young forms of cells: myeloblasts, monoblasts, miyelomonoblasta, lymphoblasts, erythroblasts, megakaryoblasts, undifferentiated blasts, atypical forms. M. G. Abramov (1979) points to predictive value of morphology of blast crisis. Treatment is less effective in the presence of nondifferentiable blasts. In peripheral blood anemia, thrombocytopenia are noted, the eosinophilic and basphilic association disappears, SOE is increased. The picture of marrowy point is characterized by a reduction of erythroidal and megakariotsitarny sprouts.
At some patients the myelosis begins with blast crisis at once. It leads to a diagnostic mistake as kliniko-hematologic data testify in favor of an acute leukosis. In the practical relation such mistake does not matter because therapy in both cases is identical. Further proceeding from character of a course of a disease establish the diagnosis of a myelosis. In case of achievement of remission the myelosis, judging by hematologic signs (a leukocytosis, neutrophylic shift to the left), enters the developed stage. At achievement of remission of an acute leukosis a normal hemopoiesis is recovered.
The juvenile type of a myelosis at children has a number of features. As it was already specified, this form occurs mainly at children of younger age. In the kariologichesky analysis do not find a specific marker — Ph' - a chromosome. The main pattern is more rapid acute current reminding an end-stage of adult type of a myelosis. N. A. Alekseev (1980) notes that at juvenile option it is difficult to allocate and differentiate the separate periods of a disease in connection with a fast progression of process. From precursory symptoms of a disease it is possible to allocate: loss of appetite, lack of an increase in body weight, a sleep disorder. In an early stage of a disease the hemorrhagic syndrome is noted. Long period. relative wellbeing is not observed. At small children the hypotrophy quickly develops. Heavy hemorrhagic manifestations are characteristic: nasal and gastrointestinal bleedings, hamaturia, emergence on skin of infiltrates of hemorrhagic character. On skin necrotic defeats and plentiful papulo-pustular rash with preferential localization on a face are noted.
Frequent sign of a juvenile form of a chronic leukosis is significant increase in lymph nodes. Lymph nodes define in all groups. They are characterized by considerable density, sometimes are soldered among themselves and to surrounding fabric. Signs of defeat of bone system — severe pain in flat and tubular bones are noted. The liver and a spleen increase, but unlike an adult form their uniform moderate increase is usually observed.
In peripheral blood normokhromny anemia, thrombocytopenia are expressed. Erythrocytes contain the increased amount of fetalis hemoglobin — 30 — 40%, sometimes to 100%. The leukocytosis is noted, however it is less expressed, than at an adult form. The quantity of leukocytes seldom exceeds 100 X 109/l, SOE is increased. In a leykogramma usually there is no eozinofilyyu-basphilic association, all transitional forms of a granulotsitarny row, blast cells are had. Increase in number of monocytes is observed. In marrowy punctate the maintenance of blast cells (myeloblasts, monoblasts, erythroblasts) is a little increased, erythroidal and megakariotsitarny sprouts are narrowed that reminds a picture of an acute leukosis and to a lesser extent more — an end-stage of an adult form of a myelosis. Additional researches show that at patients the maintenance of a lysozyme in blood serum and urine is increased. The juvenile form of a myelosis is characterized by a rapid current, a refrakternost to therapy, longevity of most of patients does not exceed one year. The general intoxication, consecutive infection (pneumonia, sepsis), the complications caused by a hemorrhagic syndrome are a cause of death at a myelosis.
Complex treatment of a myelosis is defined depending on a form of a disease and a stage of process. At treatment of the adult like therapy it is directed to stabilization of tumoral growth. For this purpose appoint Myelosanum (Myleranum, musulfan). It is the low-toxic drug operating on the stem not proliferating cells therefore the effect of action is a little delayed. Myelosanum no more than 4 mg a day appoint in a dose 0,6 — 2,0 mg/sq.m, but. The dose of Myelosanum of subjects is less, than the level of leukocytes is lower.
Now recommend an early initiation of treatment, at once after establishment of the diagnosis of a myelosis in the presence of symptoms of intoxication even if the quantity of leukocytes does not exceed 50 X 109/l. Therapy should be begun with the minimum doses, 3 — 4 times a week. Further the dose is selected individually for kliniko-hematologic dynamics and if necessary led up to maximum, drug is accepted daily. However the maximum doses it is necessary to approach treatment carefully. Sometimes the quantity of leukocytes temporarily increases in an initiation of treatment Myelosanum that is not the indication to increase in a dose. Afterwards regression of kliniko-hematologic signs is observed — the quantity of leukocytes decreases, the spleen decreases in sizes, the health of patients improves. Tactics of a miyelosanoterapiya provides an indispensable dose decline of drug twice at reduction of initial level of leukocytes twice. When falling level of leukocytes d 15 X 109 pass to a maintenance therapy (7 g of a daily dose), giving Myelosanum of 1 — 3 time a week, depending on fluctuation of level of leukocytes.
In treatment of the developed stage of a myelosis use miyelobromol. Drug, unlike Myelosanum, affects the proliferating cells therefore the effect is shown earlier. Quicker the leukocytosis decreases, intoxication decreases, the spleen is reduced. However miyelobromol is more toxic, depresses a thrombocytopoiesis. The long-term results of treatment it is also worse, recurrence of a disease comes quicker. Therefore miyelobromol recommend to apply in anticipation of blast crisis when resistance to Myelosanum develops. In this case miyelobromol gives fast and full effect. Appoint in a dose 40 — 80 mg/sq.m a day daily or every other day. After normalization of level of leukocytes pass to a maintenance therapy. In case of a blastoz in peripheral blood (to 10%) and marrow (to 20%) it is possible to appoint at the same time 6 Mercaptopurinum in a dose of 40 — 50 mg/sq.m a day daily or every other day (L. A. Makhonova and soavt., 1984).
In domestic hematology positive experience of treatment of a myelosis is saved up by hexaphosphamide, hydroxurea. In pediatric practice the alkylating drug mitolaktol is used (100 mg/sq.m a day; L. A. Makhonova and soavt., 1984).
Now seldom resort to radiation of a spleen. However in the presence of a sharp splenomegaly radiation therapy, sometimes a splenectomy is justified.
Treatment of the terminal period of an adult form of a myelosis and juvenile form carries a number of basic features. Therapy by cytostatic means according to the programs applied at the corresponding option of an acute leukosis is carried out.
Recommend schemes VAMP, TsVAM, TsOAP, inclusion in therapy of an arabinozid-tsitozin (AVAMP), rubomitsin "2 + 5" or "7 + 3". But use of polychemotherapy at a myelosis demands individualization and care at the choice of a dose of drugs. The possibility of development of a deep cytopenia is dictated by use of the minimum initial doses and careful hematologic control. In some cases achievement of remission is possible.



 
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