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The purpose of the study was to determine the main causal factors in the formation of anemia in children of Ukraine, depending on the morphometric changes in erythrocytes of blood, indicators of iron metabolism for the formation of a risk group for oncohematological diseases. Material and methods. 770 children were examined: 724 with anemia, 46 with acute lymphoblastic leukemia. We studied the parameters of the erythrocyte lineage of hematopoiesis, morphometric parameters of erythrocytes, indicators of iron metabolism (serum iron, ferritin, transferrin, the transferrin saturation with iron, hematocrit, the content of δ-aminolevulinic acid and coproporphyrin in urine, pituitary thyroid stimulating hormone depending on the type of somatic pathology. Anemic states were distributed taking into account the average erythrocyte volume and the average hemoglobin content in the erythrocyte, and dividing diagnoses microcytic-hypochromic or normocytic-normochromic anemia, respectively. Results and discussion. The study showed that in children with normocytic-normochromic anemia, the number of erythrocytes and hematocrit were lower than in patients with microcytic-hypochromic anemia, while average erythrocyte volume, average hemoglobin content, serum iron, serum ferritin and transferrin saturation with iron were higher. The number of reticulocytes in the peripheral blood in all the examined subjects was standard. That is, the anemic conditions in children differed in ferrokinetic parameters, in particular, with and without iron deficiency. Taking into account the age of the children and the reasons for the development of anemia, a third of the girls of puberty with microcytic-hypochromic anemia had menorrhagias. In children under 6 years of age with normocytic-normochromic anemia, diseases of the gastrointestinal tract were more often registered; in the older 6 years – gastrointestinal diseases, helminthiasis and allergic reactions compared with patients with microcytic-hypochromic anemia. The development of normocytic-normochromic anemia in children and the functioning of the gastrointestinal tract were influenced by drug treatment for chronic pathology in the body. All children with anemia had an irrational diet. Porphyria was diagnosed in 3.8% of children with microcytic-hypochromic anemia. In 12.7% of children with normocytic-normochromic anemia, the serum thyroid stimulating hormone level was at the upper limit of the reference value (mean 3.3±0.6) mU/L), which correlated with a reduced number of erythrocytes in blood (r = -0.65) and increased values of average erythrocyte volume (r = 0.41) and average hemoglobin content (r = 0.35), and indicates changes in the erythrocyte lineage of hematopoiesis associated with the initial manifestations of thyroid hypofunction. An excess of iron was observed in 7.1% of older boys with normocytic-normochromic anemia, which requires additional examination. In patients with acute lymphoblastic leukemia were diagnosed with normocytic-normochromic anemia of varying severity. The serum ferritin level was (272.1±28.4) ng/ml and was significantly higher than in children with normocytic-normochromic anemia. In 12 of 46 patients, transferrin saturation with iron was increased and amounted to (70.2±2.3)%. Moreover, the higher the level of serum iron and serum ferritin, the higher was the transferrin saturation with iron (rs = 0.5; rs = 0.85). An inverse correlation was established between transferrin saturation with iron, patient survival (rs = -0.45) and a higher probability of death (rs = -0.46). Conclusion. Children with normocytic-normochromic anemia require in-depth examination and constitute a risk group for the development of myelodysplastic syndrome and leukemia

Elucidation of relationship between the levels of thyroid-stimulating hormone (TSH), free serum thyroxine, serum and urine cortisol and parameters of erythroid lineage of hematopoiesis to estimate the thyroid functionin children of prepubertal, pubertal, and postpubertal age permanently residing under a low-dose radiation exposureto determine the premorbid state of thyroid function.Children aged 3 to 18 years old (n = 203) living in the most intensively radionuclide-contaminated regions of Kyiv, Zhytomyr and Chornihiv oblasts of Ukraine after the Chornobyl NPP accident wereenrolled. Complaints of ossalgia, arthralgia, fatigue, bone fractures in the history, bone dysembryogenetic stigmata,hypermobility syndrome degree, and types of somatic diseases were taken into account. Peripheral blood countparameters, biochemical indices of blood serum were studied, namely the levels of total protein, cholesterol, creatinine and alkaline phosphatase activity. Levels of the free thyroxine, pituitary TSH, serum and daily urine cortisol, anddoses of radiation exposure were determined.The radiation dose values in children ranged from (0.35 ± 0.09) mSv to (0.54 ± 0.12) mSv. There was nodifference between the parameters of erythroid lineage of hematopoiesis depending on radiation dose. At the levels of serum TSH up to 1.0 μIU/ml no correlation was found with cortisol levels; at TSH levels of 1.0-3.0 μIU/ml thecorrelation coefficient was r = 0.31; at TSH levels higher than 3.0 μIU/ml the correlation coefficient was r = 0.61probably indicating a compensatory role of adrenal cortex in children at risk of thyroid disease development. In children with joint hypermobility grade II there was a higher incidence of dentofacial anomalies (χ2 = 6.9), deformitiesof lower extremities (χ2 = 6.9), and dental caries (χ2 = 4.3) (p0.05). There was a direct correlation between theserum TSH level (over 3 μIU/ml) and micrognathia (brachygnathia) (r = 0.62) indicating the impact of thyroid disease on dentofacial development. The TSH at a level of upper limit of the reference range values may contribute toa decreased RBC count in peripheral blood, increased average volume and hemoglobin content in erythrocyte beingassociated with the initial manifestations of thyroid dysfunction.Abnormal endocrine regulation of hematopoiesis affects the connective tissue, stromal microenvironment of bone marrow, and accordingly the erythroid branch of hematopoiesis in children, which may be relevant inthe development and course of oncohematological diseases.Meta: vyvchennia zv’iazku mizh rivniamy tyreotropnogo gormonu gipofizu, vil'nogo tyroksynu, kortyzolu v syrovattsikrovi ta kortyzolu v sechi i pokaznykamy erytrotsytarnoï lanky gemopoezu u diteĭ prepubertatnogo, pubertatnogo ta pisliapubertatnogo viku, iaki zhyvut' na radioaktyvno zabrudnenykh terytoriiakh pislia avariï na ChAES, dliaotsinky funktsional'nogo stanu shchytopodibnoï zalozy.Materialy i metody. Obstezheno 203 dytyny vikom vid 3 do 18 rokiv, iaki prozhyvaiut' v naĭbil'sh zabrudnenykhradionuklidamy regionakh Kyïvs'koï, Zhytomyrs'koï ta Chernigivs'koï oblasteĭ Ukraïny pislia avariï na Chornobyl's'kiĭ AES. U diteĭ vrakhovuvaly skargy na osalgiï, artralgiï, shvydku vtomu, perelomy kistok v anamnezi,kistkovi stygmy dyzembriogenezu, stupin' gipermobil'nogo syndromu, vyd somatychnoï patologiï. Vyvchaly pokaznyky peryferychnoï krovi, biokhimichni parametry syrovatky krovi: riven' zagal'nogo bilka, luzhnoï fosfatazy,kholesterynu, kreatyninu. Vyznachaly riven' vil'nogo tyroksynu, tyreotropnogo gormonu gipofizu (TTG), kortyzolu v syrovattsi krovi ta kortyzolu v doboviĭ sechi i dozy oprominennia diteĭ.Rezul'taty. Dozy oprominennia diteĭ kolyvalys' vid (0,35 ± 0,09) mZv do (0,54 ± 0,12) mZv. Ne bulo riznytsi mizhpokaznykamy erytrotsytarnoï lanky gemopozu zalezhno vid doz oprominennia. Pry rivniakh TTG v syrovattsi krovi do1,0 mkME/ml u diteĭ ne vstanovleno koreliatsiĭnogo zv’iazku z vmistom kortyzolu; pry rivniakh TTG 1,0 mkME/ml –3,0 mkME/ml koefitsiient koreliatsiï dorivniuvav r = 0,31; pry rivniakh TTG vyshchykh za 3,0 mkME/ml zv’iazok stanovyvr = 0,61, shcho mozhe svidchyty pro kompensatornu rol' kory nadnyrkovykh zaloz u diteĭ grupy ryzyku rozvytku z tyreoïdnoï patologiï. U diteĭ z II stupenem gipermobil'nosti suglobiv sposterigaiet'sia bil'sha chastota anomaliĭ zuboshchelepnoï systemy (χ2 = 6,9), deformatsiĭ nyzhnikh kintsivok (χ2 = 6,9) ta kariiesu zubiv (χ2 = 4,3), (r0,05). Vstanovlenyĭ priamyĭ koreliatsiĭnyĭ zv’iazok mizh rivnem TTG v syrovattsi krovi (vyshchyĭ za 3,0 mkME/ml) i nedorozvynutoiu shchelepoiu u diteĭ (r = 0,62), shcho svidchyt' pro vplyv tyreoïdnoï patologiï na rozvytok zuboshchelepnogo aparatu. Riven' TTG, iakyĭ znakhodyvsia na verkhniĭ mezhi referentnykh znachen', mozhe spryiaty zmenshenniu chysla erytrotsytiv v krovi, pidvyshchenniu seredn'ogo ob’iemu ta vmistu gemoglobinu v erytrotsyti, shcho pov’iazano z pochatkovymyproiavamy porushennia funktsional'nogo stanu tyreoïdnoï systemy.Vysnovky. Naiavnist' zmin v endokrynniĭ reguliatsiï gemopoezu vplyvaie na stan spoluchnoï tkanyny, stromal'nogo mikrootochennia kistkovogo mozku diteĭ i, vidpovidno, erytrotsytarnu lanku krovotvorennia, shcho mozhe vidigravaty rol' u rozvytku ta perebigu onkogematologichnoï patologiï.

To determine the influence of iron metabolism on the prognosis of acute lymphoblastic (ALL) and (AML)myeloblastic leukemia at the different phases of chemotherapy in children after Chоrnobyl accident.333 children (295 - ALL, 38 - AML) were examined at the stages of chemotherapy. Thecomparison group included 93 children without leukemia. Acute leukemia variants, patients survival, relapses, thenature of disease (live child or died), iron methabolism (morphometric parameters of erythrocytes, SI, SF, STf, TS),manifestations of dyserythropoiesis, bone marrow sideroblast and patients radiation dose were taken into account.In 295 patients with ALL the following variants of leukemia were established: pro-B-ALL in 23, «common»type of ALL in 224, pre-B-ALL in 29, T-ALL in 19. Thirty eight patients were diagnosed with AML (11 - M1, 19 - M2,8 - M4). Doses of radiation in patients with AL were (2.78 ± 0.10) mSv and they did not correlate with clinical andhematological parameters, disease variant. Relapse rates and shorter survival were in patients with T-ALL, pro-B-ALLand AML with SF levels500 ng/ml (p0.05). The amount of children with normochromic-normocytic anemias andmanifestations of dysplasia of erythroid lineage elements was greater in the AML than in ALL. SF content in patientswas elevated during chemotherapy and was lower than the initial one only in the remission period. Transferrin wasreliably overloaded with iron: TS (70.2 ± 2.3) % compared with the control group (32.7 ± 2.1) %. Correlationbetween TS and survival of patients was detected (rs = -0.45). Direct correlation between the number of iron granules in erythrocariocytes and SF level (rs = 0.43) was established, indicating the phenomena of ineffective erythropoiesis.The negative influence of iron excess in the patients body on the hemopoiesis function, manifestations of ineffective erythropoiesis and the course of acute leukemia in children have been established. Changes inferrokinetic processes in children can be the basis of leukemоgenesis development.Meta: vyznachyty vplyv obminu zaliza na prognoz perebigu gostrykh limfoblastnykh (GLL) ta miieloblastnykh leĭkemiĭ (GML) u diteĭ pislia Chornobyl's'koï avariï na etapakh khimioterapiï.Materialy i metody. Obstezheno 333 dytyny (295 z GLL, 38 z GML) na etapakh khimioterapiï. Do grupy porivnianniauviĭshlo 93 dytyny. Vrakhovuvaly varianty gostrykh leĭkemiĭ, vyzhyvanist' khvorykh, retsydyvy, vypadky smerti, pokaznyky obminu zaliza (morfometrychni parametry erytrotsytiv, kontsentratsiia zaliza, ferytynu i transferynu usyrovattsi krovai, koefitsiient nasychennia transferynu zalizom), proiavy dyzerytropoezu, syderoblasty v kistkovomu mozku ta dozy oprominennia khvorykh.Rezul'taty. U 295 khvorykh na GLL buly vstanovleni taki varianty leĭkemiĭ: pro-V-GLL – u 23, «zagal'nyĭ» typGLL – u 224, pre-V-GLL – u 29, T-GLL – u 19. U 38 patsiientiv diagnostuvaly GML (11 – M1, 19 – M2; 8 – M4). Dozyoprominennia khvorykh na gostru leĭkemiiu stanovyly (2,78 ± 0,10) mZv i vony ne koreliuvaly z kliniko-gematologichnymy pokaznykamy ta variantom khvoroby. Chastota retsydyviv i korotsha vyzhyvanist' buly u patsiientiv, khvorykh na T-GLL, pro-V-GLL ta GML z rivniamy syrovatkovogo ferytynu ponad 500 ng/ml (r0,05). Chastka diteĭ znormokhromno-normotsytarnymy anemiiamy i proiavamy dysplaziï elementiv erytroïdnogo riadu bula bil'sha pryGML, nizh pry GLL. Vmist syrovatkovogo ferytynu u patsiientiv pidvyshchuvavsia pry provedenni khimioterapiï i buvnyzhchyĭ za pochatkovyĭ lyshe v period remisiï. Transferyn buv dostovirno perevantazhenyĭ zalizom: koefitsiientnasychennia transferynu zalizom – (70,2 ± 2,3) %, porivniano z grupoiu kontroliu – (32,7 ± 2,1) %. Vstanovleno zvorotnyĭ koreliatsiĭnyĭ zv’iazok mizh koefitsiientom nasychennia transferynu zalizom i vyzhyvanistiu khvorykh (rs = -0,45)Vstanovleno priamyĭ koreliatsiĭnyĭ zv’iazok mizh chyslom granul zaliza v erytrokariotsytakh ta rivnem syrovatkovogo ferytynu (rs = 0,43), shcho svidchyt' pro iavyshcha neefektyvnogo erytropoezu.Vysnovky. Vstanovleno negatyvnyĭ vplyv nadlyshku zaliza v organizmi khvorykh na stan gemopoezu, proiavy neefektyvnogo erytropoezu ta perebig gostrykh leĭkemiĭ u diteĭ. Zminy ferokinetychnykh protsesiv u diteĭ mozhut'lezhaty v osnovi leĭkemogenezu.

to assess the thyroid disease in the late observation period in children who had received chemo- andradiotherapy for the acute lymphoblastic leukemia (ALL) taking into account gender, age period and disease sub-type.The incidence and nature of thyroid disease (hypothyroidism, thyroiditis, and thyroid can-cer) were studied in children-survivors of acute lymphoblastic leukemia (ALL) being in remission from 6 to 25 years.The distribution of patients by leukemia subtypes was as follows: «common» - 67.4 %, pre-B - 23.9 %, pro-B andT-cell - 4.3 %. Children had been receiving chemo- and radiotherapy according to the protocol. Regarding the ageof patients at the time of ALL diagnosis the prepubertal, pubertal and postpubertal periods were taken into account.The endocrine diseases in family history, body weight at birth, serum content of free thyroxine, pituitary thyroid-stimulating hormone, cortisol, iron, ferritin and thyroperoxidase antibodies were evaluated and assayed.Thyroid disease in children was emerging in the first 2-3 years after the ALL treatment with an incidenceof 22.8 % (hypothyroidism - 14.1 %, autoimmune thyroiditis - 7.6 %, papillary cancer - 1.1 %). Seven children inthis group had received radiotherapy (12-18 Gy doses) on the central nervous system (CNS). No correlation wasfound between the radiation exposure event itself, radiation dose to the CNS and thyroid disease in the long-termfollow-up period. Thyroid cancer had developed in a child 11 years upon chemo- and radiotherapy. Hypothyroidismwas more often diagnosed in the patients of prepubertal age (rs = 0.49). There were endocrine diseases in thefamily history in about a half of children, being significantly higher than in the general sample (р0.05). The bodyweight at birth of a child who had later developed hypothyroidism was less than in children having got thyroiditis(rs = 0.57).Disorders in endocrine regulation and of thyroid in particular can affect the prognosis of blood can-cer course in the long-term follow-up in children, especially in prepubertal age, which requires systematic supervi-sion by hematologist and endocrinologist.Meta: otsinyty patologiiu shchytopodibnoï zalozy u diteĭ, iaki otrymuvaly khimio- ta promenevu terapiiu z pryvodugostroï limfoblastnoï leĭkemiï, u viddalenomu periodi sposterezhennia z urakhuvanniam stati, vikovoï periodyzatsiïta variantiv khvoroby.Materialy i metody. U 92 diteĭ z gostroiu limfoblastnoiu leĭkemiieiu, iaki znakhodiat'sia v remisiï vid 6 do 25 rokiv,vyvchaly chastotu ta kharakter patologiï shchytopodibnoï zalozy (gipotyreoz, tyreoïdyt, rak). Rozpodil khvorykh zavariantamy leĭkemiĭ buv takyĭ: «zagal'nyĭ» typ – 67,4 %, pre-V – 23,9 %, pro-V ta T-klitynnyĭ po 4,3 %. Dityotrymuvaly khimio- ta promenevu terapiiu zgidno z protokolom. Shchodo viku khvorykh na chas vstanovlennia diagnozugostroï limfoblastnoï leĭkemiï, to vrakhovuvaly prepubertatnyĭ, pubertatnyĭ ta pislia pubertatnyĭ periody.Otsiniuvaly endokrynni khvoroby v rodovodi, masu tila pry narodzhenni dytyny, vmist vil'nogo tyroksynu, tyre-otropnogo gormonu gipofizu, kortyzolu, zaliza ta ferytynu i antytila do tyreoperoksydazy v syrovattsi krovi. Rezul'taty. Patologiia shchytopodibnoï zalozy u diteĭ vynykala v pershi 2–3 roky pislia kursu terapiï i stanovyla22,8 % (gipotyreoz – 14,1 %, autoimunnyĭ tyreoïdyt – 7,6 %, papiliarnyĭ rak – 1,1 %). Semero diteĭ tsiieï grupyproĭshly promenevu terapiiu v dozakh 12–18 Gr na tsentral'nu nervovu systemu. Ne bulo vstanovleno kore-liatsiĭnogo zv’iazku mizh faktom oprominennia, dozoiu promenevogo navantazhennia na tsentral'nu nervovu systemu ipatologiieiu shchytopodibnoï zalozy u viddalenyĭ period sposterezhennia. Rak shchytopodibnoï zalozy rozvyvsia u dy-tyny cherez 11 rokiv pislia khimio- ta promenevoï terapiï. Gipotyreoz chastishe diagnostuvavsia u khvorykh prepuber-tatnogo viku (rs = 0,49). U polovyny diteĭ v rodovodi bula endokrynna patologiia, shcho virogidno vyshche, nizh u za-gal'niĭ vybirtsi (r0,05). Masa tila pry narodzhenni dytyny, u iakoï v podal'shomu rozvynuvsia gipotyreoz bulamenshoiu, nizh u diteĭ z tyreoïdytamy (rs = 0,57). Vysnovky. Zminy v endokrynniĭ reguliatsiï organizmu, zokrema shchytopodibniĭ zalozi, mozhut' vplyvaty na prognozperebigu zloiakisnykh zakhvoriuvan' systemy krovi u diteĭ, osoblyvo prepubertatnogo viku, u viddalenomu periodisposterezhennia, shcho potrebuie systematychnogo nagliadu likaria gematologa ta endokrynologa.

Estimation of the bone marrow haemopoietic status depending on the reasons and duration of breaks in a standard chemotherapy (BFM-ALL protocol) to predict the course of acute lymphoblastic leukemia (ALL) in chil- dren exposed to low doses of ionizing radiation after the Chornobyl accident.The ALL patients (n = 34) were examined within 5 stages of a program chemotherapy. The clinical symptoms, hemogram and myelogram data were analyzed. The radiation dose on bone marrow, initial leuko- cyte count, variants and prognosis of ALL course were accounted. Days of the stopped chemotherapy, type and fre- quency of complications (septic processes, febrile neutropenia, toxic hepatitis, granulocytopenia degree), and the prognosis of disease course (child living status, i.e. alive or died) were estimated.There were abnormal differentiation processes and high percentage of lymphoblasts (86.2 ± 3.3) % in bone marrow in the 1st acute period. Hematological remission was established in all patients on the 33rd day of chemothe- rapy. In a half of cases the haematopoietic recovery occurred by a granulocyte-monocyte type. One third of patients presenting an erythroid type of haemopoiesis died later. The inverse correlation was found between the number of myelocaryocytes and disease prognosis (rs = -0.49). Breaks in chemotherapy for various reasons were recorded. The number of patients with granulocytopenia was greater at the phase 1 and 2 of protocol I and protocol M application, coinciding with a higher incidence of complications. An inverse correlations between the prediction of ALL course and sum of days of breaks between the protocol M and phase 1 of protocol II (rs = -0.56), as well as the duration of the phase 2 of protocol II (rs = -0.62) were found. The radiation dose on bone marrow was (5.37 ± 1.23) mSv. No relationship was found between the radiation doses, ALL variants and disease course.Prognosis of ALL course in children depends on the type of haemopoietic recovery and reasons of breaks in a standard chemotherapy. Interaction between the haemopoiesis functioning and microenvironment and that of their regulation are the key mechanisms of above-mentioned abnormalities, which is the basis for further research.Meta: otsinyty stan kistkovomozkovogo krovotvorennia zalezhno vid prychyn i tryvalosti pererv pry provedenni standartnoï khimioterapiï za protokolom BFM-ALL dlia prognozu perebigu gostrykh limfoblastnykh ley̆kemiy̆ (GLL) u ditey̆, iaki zaznaly vplyvu malykh doz ionizuiuchogo vyprominiuvannia vnaslidok avariï na ChAES.Materialy i metody. Obstezheno 34 khvorykh na GLL na 5 etapakh programnoï khimioterapiï. Vyvchaly klinichnu symp- tomatyku, pokaznyky gemogram i miielogram. Vrakhovuvaly dozy oprominennia na kistkovyy̆ mozok, initsial'ne chys- lo ley̆kotsytiv, varianty ta prognoz perebigu GLL. Otsiniuvaly kil'kist' dniv zupynok pry provedenni khimioterapiï, vyd i chastotu uskladnen' (septychni protsesy, febryl'nu ney̆tropeniiu, toksychnyy̆ gepatyt, stupin' granulotsyto- peniï) ta prognoz perebigu zakhvoriuvannia (zhyva zhytyna chy pomerla).Rezul'taty. V I gostryy̆ period u khvorykh v kistkovomu mozku maly mistse zminy protsesiv dyferentsiiuvannia i vy- sokyy̆ vidsotok limfoblastiv (86,2 ± 3,3) %. Na 33-y̆ den' khimioterapiï u vsikh khvorykh bulo konstatovano gemato- logichnu remisiiu. U polovyny khvorykh krovotvorennia vidnovliuvalos' za granulotsytarno-monotsytarnym typom. Tretyna khvorykh, u iakykh sposterigavsia erytroïdnyy̆ typ gemopoezu, v podal'shomu pomerly. Vstanovleno zvorot- nyy̆ koreliatsiy̆nyy̆ zv'iazok mizh kil'kistiu miielokariotsytiv i prognozom perebigu zakhvoriuvannia (rs = -0,49). Pry provedenni khimioterapiï u ditey̆ buly perervy v likuvanni z riznykh prychyn. Chyslo khvorykh z granulotsytopeniieiu bulo bil'shym na 1-y̆ i 2-y̆ fazi protokolu I ta protokoli M, i tse spivpadalo z bil'shoiu chastotoiu uskladnen'. Vsta- novleno zvorotni koreliatsiy̆ni zv'iazky mizh prognozom perebigu GLL i sumoiu dniv pererv mizh protokolom M ta 1-iu fazoiu protokolu II (rs = -0,56), a takozh tryvalistiu 2-ï fazy protokolu II (rs = -0,62). Doza na kistkovyy̆ mozok u ditey̆ dorivniuvala (5,37 ± 1,23) mZv. Ne vyznacheno zv'iazku mizh dozamy oprominennia khvorykh, variantamy GLL i perebigom zakhvoriuvannia.Vysnovky. Prognoz perebigu GLL u ditey̆ zalezhyt' vid typu vidnovlennia krovotvorennia ta prychyn pererv pry provedenni standartnoï khimioterapiï. V osnovi vyznachenykh zmin lezhat' mekhanizmy vzaiemodiï mizh funktsionuvan- niam gemopoezu, mikrootochenniam ta ïkh reguliatsiieiu, shcho ie pidgruntiam dlia podal'shogo vyvchennia.

establishing the types and frequency of disembriogenetic stigma in children with joint hypermobility given the clinical and laboratory features, genetic component and endocrine regulation of these disorders in a late period upon the accident.Children (n = 109) inhabiting the radiologically contaminated territories and having the connective tissue dysplasia (CTD) signs were involved in the study. Diseases in family history, ossalgia complaints, fractures in a personal history, bone disembriogenetic stigma, joint hypermobility, type of somatic diseases, blood serum biochemical parameters (namely calcium, alkaline phosphatase, total protein, cholesterol, creatinine, iron, ferritin content), serum cortisol, free thyroxine, pituitary thyroid-stimulating hormone (TSH) levels, free amino acid composition in urine and radiation dose were considered.Radiation doses in children having the CTD ranged from (0.37 ± 0.11) mSv to (0.56 ± 0.10) mSv with no difference from that in those without CTD. Joint hypermobility (JHM) correlated with cancer in family history (rs = 0.53) and lower extremity varicose vein disease (rs = 0.40) (p0.05). Incidence of ossalgia, easy fatigability, and bone fractures was higher in children with CTD. Anomalies of the dentofacial system were first in line (38.5 %) in these children. Proportion of children with grade II JHM and platypodia was lower (rs = 0.42), but with lower extremity deformations was higher (rs = 0.68) (p0.05) vs. in the control group. Iron and ferritin deficiencies both with lymphocytosis were more common in children with CTD than in the comparison group (p0.05). The increased content of oxyproline, lysine, proline both with glycine deficiency were detected in children having the CTD, i.e. an imbalance of amino acids from the collagen content was observed featuring a predominance of catabolic processes over anabolic ones. There was a direct correlation between the TSH level and the JHM grade (rs = 0.49), although the values of hormone concentration in these children did not exceed the reference range (maximum values were 3.3 μIU/ml).The revealed abnormalities in amino acid content, ferrokinetics, and thyroid function indices can affect the collagen formation, organic matrix structure of bone tissue and significantly deregulate the hemato- poiesis. The later can underlie the pathways of haematologic malignancy development.Meta: vstanovyty vydy ta chastotu stygm dyzembriogenezu u ditey̆ z gipermobil'nistiu suglobiv z urakhuvanniam kliniko-laboratornykh osoblyvostey̆, genetychnoï komponenty ta endokrynnoï reguliatsiï tsykh rozladiv u viddale- nyy̆ pisliaavariy̆nyy̆ period.Materialy i metody. Obstezheno 109 ditey̆ – zhyteliv kontaminovanykh radionuklidamy terytoriy̆, z proiavamy dysplaziï spoluchnoï tkanyny (DST). Vrakhovuvaly khvoroby u rodovodi, skargy ditey̆ na osalgiï, perelomy kistok v anamnezi, kistkovi stygmy dyzembriogenezu, naiavnist' gipermobil'nosti suglobiv, vyd somatychnoï patologiï, biokhimichni pokaznyky krovi (riven' kal'tsiiu, luzhnoï fosfatazy, zagal'nogo bilka, kholesterynu, kreatyninu, zaliza, ferytynu), riven' kortyzolu, vil'nogo tyroksynu, tyreotropnogo gormonu gipofizu (TTG), sklad vil'nykh aminokyslot v sechi ta dozy oprominennia.Rezul'taty. Dozy oprominennia ditey̆ z DST kolyvalys' vid (0,37 ± 0,11) mZv do (0,56 ± 0,10) mZv i ne vidriznia- lys' vid doz osib bez DST. Gipermobil'nist' suglobiv (GMS) u ditey̆ koreliuvala z naiavnistiu u rodovodi onko- logichnykh zakhvoriuvan' (rs = 0,53) i varykoznoï khvoroby nyzhnikh kintsivok (rs = 0,40) (r0,05). Chastota osalgiy̆, shvydkoï vtomliuvanosti i perelomiv kistok bula vyshchoiu u ditey̆ z DST. Na pershomu mistsi u tsykh ditey̆ znakhodylys' chastota anomaliy̆ rozvytku zuboshchelepnoï systemy (38,5 %). Chastka ditey̆ z GMS II stupenia z ploskostopistiu bu- la nyzhchoiu (rs = 0,42), a z deformatsiieiu nyzhnikh kintsivok – vyshchoiu (rs = 0,68) (r0,05), nizh u grupi kontroliu. Defitsyt zaliza, ferytynu i limfotsytozy sposterigalys' chastishe u ditey̆ z DST, nizh v grupi porivniannia (r0,05). U ditey̆ z DST buv pidvyshchenym vmist oksyprolinu, lizynu, prolinu i vyiavliavsia defitsyt glitsynu, tobto sposterigav- sia dysbalans aminokyslot, iaki vkhodiat' do skladu kolagenu, perevazhannia katabolichnykh protsesiv nad anabolichny- my. Vstanovleno priamyy̆ koreliatsiy̆nyy̆ zv’iazok mizh rivnem TTG i stupenem GMS (rs = 0,49), khocha znachennia kontse- ntratsiï TTG v krovi tsykh ditey̆ ne perevyshchuvaly referentni (maksymal'ni velychyny stanovyly 3,3 mkME/ml). Vysnovky. Vyznacheni zminy u skladi aminokyslot, ferokinetychnykh protsesakh, pokaznykakh funktsiï shchytopodibnoï zalozy mozhut' vplyvaty na kolagenoutvorennia, strukturu organichnogo matryksu kistkovoï tkanyny ta suttievo de- reguliuvaty protsesy krovotvorennia, shcho mozhe lezhaty v osnovi mekhanizmiv rozvytku onkogematologichnoï patologiï.

to establish the relationship between quantitative and qualitative parameters of peripheral blood cells(lymphocytes, neutrophilic granulocytes, monocytes, platelets) depending on the type of somatic diseases andannual internal radiation doses from 137Cs in children - residents of radiologically contaminated territories in thelate period after the Chornobyl Nuclear Power Plant (ChNPP) accident.There were 175 children included in the study comprising residents of radiologically con-taminated territories (n = 79) aged from 4 to 18 years. Annual internal radiation doses in children from 137Cs rangedfrom 0.004 to 0.067 mSv. Certain blood parameters were assessed in a comparative mode in children having got theradiation doses up to 0.01 mSv and higher. The comparison group (n = 96) included children living in settlementsnot attributed to the radiologically contaminated ones. Incidence and type of somatic diseases and its impact onquantitative and qualitative changes in blood parameters (i.e. lymphocyte, neutrophilic granulocyte, monocyte, andplatelet count) were studied. The cell size, state of nucleus, membranes and cytoplasm, signs of proliferative anddegenerative processes were taken into account.Incidence and type of somatic diseases in children did not depend on the annual internal radiation dose.Number of cases of monocytosis was significantly higher among the children exposed to ionizing radiation than inthe comparison group (16.6 % vs. 7.3 %). There were, however, no correlation between these changes and radiationdoses. Number of activated blood monocytes with cytoplasmic basophilia and residues of nucleoli in nuclei washigher in individuals with internal radiation doses0.01 mSv. A direct correlation between the qualitative param-eters of monocytes and internal radiation doses was established (rs = 0.60; р0.001), as well as a direct correlationof different strength between qualitative parameters of blood cells, indicating their unidirectional pattern depend-ing on the somatic morbid conditions. Regardless of annual internal radiation dose, there was an increase in thenumber of degenerative and aberrant cells vs. the comparison group (р0.05), which could be due to the role ofnon-radiation factors.Results of the assessment of quantitative and qualitative parameters of peripheral blood cells reflect-ed the state of morbid conditions in children and are of a diagnostic value. The identified dose-dependent changesin monocyte lineage of hematopoiesis may be the markers of impact of long-term radionuclide incorporation withfood in children living in environmentally unfavorable conditions after the ChNPP accident.Meta: vstanovyty zv’iazok mizh kil'kisnymy ta iakisnymy pokaznykamy elementiv peryferychnoï krovi (limfotsyta-my, neĭtrofilamy, monotsytamy, trombotsytamy) zalezhno vid vydu somatychnoï patologiï i richnykh doz vnutrishn'o-go oprominennia vid 137Cs diteĭ – meshkantsiv radioaktyvno zabrudnenykh terytoriĭ u viddalenyĭ period pisliaavariï na ChAES. Materialy i metody. Obstezheno 175 diteĭ. 79 diteĭ – meshkantsi radioaktyvno zabrudnenykh terytoriĭ, vikom vid4 do 18 rokiv. Richni dozy vnutrishn'ogo oprominennia diteĭ vid 137Cs kolyvalys' vid 0,004 mZv do 0,067 mZv. Pro-vedena porivnial'na otsinka vyznachenykh pokaznykiv krovi u diteĭ z dozamy oprominennia do 0,01 mZv ta vyshchymy.Grupu porivniannia sklaly 96 diteĭ – z chysla meshkantsiv naselenykh punktiv, iaki ne vidneseni do radioaktyvno zab-rudnenykh. Vyvchaly chastotu ta typ somatychnoï patologiï i ïï vplyv na kil'kisni ta iakisni zminy pokaznykiv krovi(limfotsyty, neĭtrofily, monotsyty, trombotsyty). Braly do uvagy rozmiry klityn, stan iadra, membrany ta tsytop-lazmy, oznaky proliferatyvnykh i degeneratyvnykh protsesiv. Rezul'taty. Chastota ta vyd somatychnoï patologiï u diteĭ ne zalezhaly vid richnoï dozy vnutrishn'ogo oprominennia.Chyslo diteĭ z monotsytozamy bulo dostovirno bil'shym sered oprominenykh diteĭ, nizh v grupi porivniannia (16,6 %proty 7,3 %), khocha tsi zminy ne koreliuvaly z dozamy oprominennia. Kil'kist' aktyvovanykh monotsytiv u krovi z ba-zofiliieiu tsytoplazmy i zalyshkamy nukleol v iadri bula bil'shoiu u osib z dozamy vnutrishn'ogo oprominennia, vy-shchymy za 0,01 mZv. Vstanovleno priamyĭ koreliatsiĭnyĭ zv’iazok mizh iakisnymy oznakamy monotsytiv z dozamyvnutrishn'ogo oprominennia dytyny (rs = 0,60; r0,001), a takozh vyznacheni priami koreliatsiĭni zv’iazky riznogo stu-penia tisnoty mizh iakisnymy oznakamy v elementakh krovi, shcho svidchat' pro ïkhniu odnospriamovanu napravlenist' za-lezhno vid patologichnykh staniv v organizmi. Nezalezhno vid richnoï dozy vnutrishn'ogo oprominennia diteĭ spos-terigalos' zbil'shennia chysla degeneratyvnykh ta aberantnykh klityn, porivniano z grupoiu porivniannia (r0,05),shcho, mozhlyvo, pov’iazano z vplyvom neradiatsiĭnykh chynnykiv. Vysnovky. Rezul'taty otsinky kil'kisnykh ta iakisnykh pokaznykiv v elementakh peryferychnoï krovi vidobrazhaiut'stan patologichnykh protsesiv v organizmi dytyny i maiut' diagnostychnu tsinnist'. Vyznacheni dozozalezhni zminy umonotsytarniĭ lantsi gemopoezu mozhut' buty markeramy vplyvu tryvalogo nadkhodzhennia radionuklidiv z produk-tamy kharchuvannia u diteĭ, iaki prozhyvaiut' v ekologichno nespryiatlyvykh umovakh pislia avariï na ChAES.

Assessment of role of the bone marrow colony-forming efficiency in plasma cell myeloma patients at different stages of treatment as a prognostic criterion for the disease course.The colony forming efficiency (CFE) was assayed in stage I-II plasma cell myeloma (PCM)patients (n = 37) aged 42-73, namely in patients survived after the Chornobyl NPP accident (n = 21) and persons notexposed to ionizing radiation (n = 16). There were 11 males exposed to ionizing radiation and having got stage I PCM,9 males and 3 females exposed and having got stage II PCM, 3 males and 3 females not exposed and having got stageI PCM, 6 males and 2 females not exposed and having got stage II PCM. Healthy persons (n = 20) were included in thecontrol group.Number of the bone marrow (BM) granulocyte-macrophage colony-forming units (CFU-GM) in both exposedand not exposed PCM patients depended on a disease stage. CFU-GM was (16.7 ± 1.2) in the stage I PCM patients vs.(11.1 ± 1.1) in the stage II PCM ones both being lower (p0.05) compared to control (64.5 ± 2.2). Changes in cluster formation were similar, i.e. (37.7 ± 1.6) and (19.4 ± 1.3) correspondingly in the stage I and stage II PCM patients.Respective values in control were (89.8 ± 3.6). The CFE in stage I and stage II PCM patients at the time of diagnosiswas lower (5.7 ± 1.5 and 2.4 ± 1.1 respectively) vs. control (39.5 ± 1.51, p0.05), but has increased in remission upto (29. 6 ± 1.8) and (13.8 ± 1.2) respectively. There was no difference at that between the irradiated and non-irradiated patients. Number of the fibroblast colony-forming units (CFU-F) in the stage I and stage II PCM patients duringdiagnosis, namely (43.9 ± 5.4) and (22.5 ± 3.7), was lower (p0.05) vs. control (110.5 ± 4.9). Upon reaching remission the CFU-F value increased significantly (p0.05), reaching (87.4 ± 4.2) and (55.6 ± 2.7) correspondingly in thestage I and stage II PCM patients.Dependence of the BM cell CFE on the stage of PCM and presence or absence of remission was established. Prognostic value of the CFE of BM CFU-GM in terms of life span of patients was shown (Ro Spearm = 0.39,p0.02), namely in case of CFE20 before the polychemotherapy administration the life span of PCM patients wassignificantly longer vs. cases of CFE20.Meta roboty: na osnovi doslidzhennia efektyvnosti koloniieutvorennia klityn kistkovogo mozku khvorykh na plazmoklitynnu miielomu na riznykh etapakh likuvannia otsinyty ïï znachennia iak prognostychnogo kryteriiu perebigu zakhvoriuvannia.Materialy i metody. Efektyvnist' koloniieutvorennia (EKU) otsineno u 37 patsiientiv vikom 42–73 rokiv z plazmoklitynnoiu miielomoiu (PKM) I–II ct.: 21 patsiienta, postrazhdalogo vnaslidok avariï na Chornobyl's'kiĭ AES, ta16 neoprominenykh khvorykh. Sered oprominenykh z I st. obstezheno 11 cholovikiv, sered khvorykh z II st. – 9 cholovikivta 3 zhinok, sered neoprominenykh z I st. – 3 cholovikiv, 3 zhinok, sered patsiientiv z II st. – 6 cholovikiv ta 2 zhinok.Kontrol'nu grupa sklaly 20 zdorovykh osib.Rezul'taty. Kil'kist' koloniieutvoriuiuchykh granulotsytarno-makrofagal'nykh odynyts' (KUO-GM) kistkovogo mozku (KM) khvorykh na PKM ob’iednanoï grupy (opromineni, neopromineni) zalezhala vid stadiï zakhvoriuvannia. U khvorykh z I st. KUO-GM stanovyla 16,7 ± 1,2 proty 11,1 ± 1,1 pry II st. i bula nyzhchoiu (p0,05), porivniano z kontrolem (64,5 ± 2,2). Podibnymy buly zminy pry utvorenni klasteriv (I st. – 37,7 ± 1,6; II st. – 19,4 ± 1,3; kontrol' –89,8 ± 3,6). U khvorykh z I ta II st. na moment diagnostyky EKU bula nyzhchoiu (5,7 ± 1,5 ta 2,4 ± 1,1 vidpovidno),porivniano z kontrolem (39,5 ± 1,51, p0,05), pry remisiï EKU zrostala (29,6 ± 1,8 ta 13,8 ± 1,2 vidpovidno). Pokaznyky oprominenykh i neoprominenykh patsiientiv ne vidriznialys'. Na etapi diagnostyky kil'kist' koloniieutvoriuiuchykh odynyts' fibroblastiv (KUO-F) bula nyzhchoiu (p0,05), porivniano z kontrolem (110,5 ± 4,9) – 43,9 ± 5,4 ta22,5 ± 3,7 u patsiientiv z I ta II st. PKM vidpovidno. Pry dosiagnenni remisiï KUO-F zrostala (p0,05): u khvorykh zI st. PKM KUO-F siagala 87,4 ± 4,2; u patsiientiv z II st. – 55,6 ± 2,7.Vysnovky. Vstanovlena zalezhnist' EKU klityn KM vid stadiï PKM ta naiavnosti/vidsutnosti remisiï. Pokazanoprognostychne znachennia pokaznyka EKU KUO-GM KM shchodo tryvalosti zhyttia patsiientiv (Ro Spearm = 0,39, p0,02):za naiavnosti EKU20 do provedennia polikhimioterapiï tryvalist' zhyttia khvorykh na PKM bula suttievo dovshoiuporivniano z patsiientamy, u iakykh pokaznyk EKU20.

Patients with acute leukemia were examined before the start of chemotherapy (CT), and after the І-st and ІІ-nd phase of CT. According myelogram data the bone marrow recovery after myelosuppression occured with predominance with one of these links of hematopoiesis: erythroid, granulocyte, granulocyte-monocyte, monocyte and uniform mixed types. It is shown, that in the ІІ-nd examination phase the reduced number of cases with erythroid recovery prevalence were existed and the number of children with activation of granulocyte compound of hematopoiesis were increased compared to the І-st phase of СТ. Indices of megakaryocyte link in both periods of chemotherapy practically were no different. The correlation between the percentage of erythroid cells in myelogram and child survival were established: if the of erythroid cells in the first stage of treatment exceeded 30 %, the survival of patients with acute leukemia decreased (U test. – 39) and it can serve as the additional criterion for detection of high risk patients and correction of further chemotherapy.

OBJECTIVE Determine of the influence of adverse environmental factors, including irradiation, on the survival ofchildren with acute leukemia in the long-term period after the Chornobyl accident (2008-2017). MATERIALS AND METHODS Examined 74 children with acute leukemia (АL): 64 with acute lymphoblastic leukemia(ALL); 10 - acute myeloblastic leukemia (AML). The influence of negative environmental factors was assessed bythe degree of integrated pollution of the atmospheric air, surface waters and soils with pesticides, heavy metals (Pb,Cu, Ni, Cr, Mn, Zn, Fe) and cesium isotope 137Cs. These regions were ranked on a moderately polluted (1), polluted (2),very (3) and extremely (4) polluted territories. Took into account the age of children, blood test, immunophenotyp-ic of variant the acute leukemia, survival of patients and place of residence (city / village), serum ferritin level (SF). RESULTS Exposure doses of children were in the range from 0.4 mSv to 35.0 mSv (average values were (4.25 ± 0.63 mSv)and did not affect the prognosis and variants of AL. 52 children lived in moderately and polluted territories (30 wereresidents of cities, 22 - villages). 22 patients were lived in very and extremely polluted territories (4 were residentsof cities, 18 - villages). Of 74 patients with ALL and AML 24 children died (32.4 %). The smallest number ofchildren, who died, were patients with «general type» В-ALL (18.7 %), most of all children with pro-В-ALL (8 out of10) and Т-ALL (3 of 4). Of the 52 patients, the inhabitants of moderately and polluted regions, 13 patients died (25%), while out of 22 patients, who lived in very and extremely polluted areas, 11 children died (50 % share)(rs = 0.39; p < 0.05). Of the 10 patients with AML, 4 children died. Most often, children died, who were residents ofvillages. Moreover, the level of SF was significantly higher in children over 6 years, the inhabitants of villages -(406.8 ± 40.6) ng/ml, compared to younger patients - (211.2 ± 32.1) ng/ml) and residents of of cities: up to 6years - (297.4 ± 52.3) ng/ml; over 6 years - (275.6 ± 29.8) ng/ml. CONCLUSIONS The obtained data testify to the negative influence of environmental factors, including iron, and canbe the basis for understanding the mechanisms of potentiating influence of metals and their compounds on thedevelopment of malignant diseases of the blood system in children.

OBJECTIVE Determination of serum cortisol level in the initial period of acute leukemia in children, who exposed to ion izing radiation and other factors of Chornobyl accident, depending on their age and prognosis of disease. MATERIALS AND METHODS The study involved 283 children residents of Kyiv, Zhytomyr and Chernihiv regions. There were 90 acute leukemia patients(AL) (ALL - 56, AML - 34), and 193 people of comparison group with anemia, leukemoid reactions and lymphadenopathy. We analyzed the type of comorbid somatic pathology, diseases in the genealogy, hematological parameters, cortisol levels in blood serum and irradiation doses in all children. In patients with AL expected median survival was calculated. RESULTS In 28.9 % of AL children the initial cortisol content was below 200 nmol/l, in 7.8 % - higher than 500 nmol/l (in the comparison group 10.4 % and 17.1 % respectively). Among AL patients with cortisol levels below 200 nmol/l were significantly less amount of persons with chronic bacterial infections and persistent viral infections (CMV, EBV) and in the genealogy of these children allergic reactions, endocrine pathology diagnosed more often compared with patients, whose hormone levels was higher than 200 nmol/l (p < 0.05). Distribution of children from control group by gradations of cortisol, age groups, defined somatic pathology and diseases in genealogy had no difference. It is shown, that lower initial blood serum cortisol level in ALL children correlates to a greater probability of relapse (Rs = -0,67). In patients with AML a direct correlation between cortisol level and median survival was detected (Rs = 0,79). Children radiation doses were ranging from 0.08 mSv to 14.9 mSv, and there were slightly higher among residents of Zhytomyr region (8.4 ± 1.2 mSv) compared to other regions. However, these doses did not affect blood serum cortisol levels in children and the course of AL. CONCLUSIONS These data suggest the need for correction and individualization of corticosteroid doses for optimization of AL patients treatment. Children, who have lower than normative serum cortisol levels are at increased risk of hema tologic pathology and they need for hematologic monitoring.

Experimental study of the effect profile of bortezomib in the plasma cell myeloma (PCM) patients depend- ing on a specific phenotype carrier state and a pharmacochemical characteristics of ABO system glycoproteins.The research was conducted on the 104 PCM patients, including the Chornobyl NPP acci- dent survivors (n = 49) and 65 study subjects in the comparison group. Immunogenetic criteria for positive response to the applied treatment protocols were issued according to the duration of remission, absence of infectious com- plications, and evidence of chronic renal failure as a disease complication.Possibility of glycoproteins A and B participation in the formation of human biological individuality at a level of protein-protein interaction with antineoplastic drug bortezomib, which is widely used in cancer management prac- tice, in particular in the PCM treatment is considered. The glycoprotein B was shown being a selective target for borte- zomib, slowing down the recognition and interaction of antigen B with monoclonal anti-B antibody, while the agglu- tination period lengthens at that by 66 %. Assumption that the formation of bortezomib complex with glycoprotein B provides a background for interaction with the key reaction of proteasome 26S inhibition, which to some extent con- tributes to the drug effect retardation was confirmed through the quantum-chemical calculations. Equilibrium is shift- ed toward the main reaction leading to a higher drug efficacy in patients with blood groups O (I) and A (II).Since the complexation occurs predominantly in alkaline medium the administration of drugs with alkaline reaction should be restricted for at least round the clock after administration of bortezomib according to its half-life in plasma in patients with B (III) blood group and chronic renal failure.Meta roboty – eksperymental'ne doslidzhennia osoblyvostey̆ diï preparatu bortezomib u khvorykh na plazmokli- tynnu miielomu (PKM) zalezhno vid nosiy̆stva konkretnogo fenotypu i farmakokhimichnoï kharakterystyky glikopro- teïniv systemy AVO.Materialy i metody. Doslidzhennia provedeni u 104 khvorykh na PKM, sered nykh – 49 osib, postrazhdalykh vnaslidok avariï na ChAES, ta 65 patsiientiv grupy porivniannia. Imunogenetychni kryteriï pozytyvnoï vidpovidi na likuval'ni programy vyznachaly na osnovi tryvalosti remisiï, vidsutnosti infektsiy̆nykh uskladnen' i stupenia naiavnosti khronichnoï nyrkovoï nedostatnosti iak uskladnennia zakhvoriuvannia.Rezul'taty. Rozglianuta mozhlyvist' uchasti glikoproteïniv A i V u formuvanni biologichnoï indyvidual'nosti liudy- ny na rivni bilok-bilkovoï vzaiemodiï z likars'kym protypukhlynnym preparatom bortezomibom, iakyy̆ shyroko za- stosovuiet'sia v onkologichniy̆ praktytsi, zokrema pry likuvanni PKM. Dovedeno, shcho selektyvnoiu mishenniu dlia bor- tezomibu ie glikoproteïn V, shcho upovil'niuie rozpiznavannia i vzaiemodiiu antygena V z monoklonal'nym anty-V an- tytilom, pry ts'omu termin agliutynatsiï podovzhuiet'sia na 66 %. Kvantovo-khimichni rozrakhunky pidtverdyly prypu- shchennia, shcho reaktsiia utvorennia kompleksu bortezomibu z glikoproteïnom V skladaie pidgruntia formuvannia vzaie- modiï z osnovnoiu reaktsiieiu ingibuvannia proteasomy 26S, shcho, pevnoiu miroiu, spryiaie upovil'nenniu diï preparatu. Dlia patsiientiv z grupamy krovi O (I) i A (II) rivnovaga zmishchuiet'sia v bik osnovnoï reaktsiï, shcho zumovliuie vyshchu efek- tyvnist' preparatu.Vysnovky. Oskil'ky kompleksoutvorennia vidbuvaiet'sia perevazhno v luzhnomu seredovyshchi, patsiientam z grupoiu krovi V (III) ta naiavnoiu khronichnoiu nyrkovoiu nedostatnistiu rekomendovano obmezhuvaty vvedennia preparativ z luzhnoiu reaktsiieiu shchonay̆menshe protiagom doby pislia vvedennia bortezomibu, vidpovidno do periodu y̆ogo napiv- rozpadu v plazmi.

OBJECTIVE Evaluation of proliferation and differentiation processes of progenitor cells in bone marrow by the com position of elements of erythroid, granulocyte and platelet branches of hematopoiesis on the treatment stages in children with acute lymphoblastic leukemia (ALL), who were exposed to radiation from the Chornobyl NPP accident. MATERIALS AND METHODS The 46 children with ALL were studied, who lived in Kyiv, Zhytomyr and Chernihiv regions. Studies were conducted before the start of chemotherapy (ChT), on the 33 day of ChT (phase I), and after the com pletion of ChT (phase II). Exposure doses of patients, hemogram and myelogram parameters both with indices of mat uration of progenitor cells were evaluated. Signs of dysplasia of hematopoietic branch elements were revewed. RESULTS The 46 patients were studied. They have had the B ALL, namely pro B ALL (n=5), «common type» (n=36), pre B ALL (n=3), and T ALL in 2 other cases. In a debut of ALL the bone marrow was represented by lymphoblasts. Along with ChT conduction the bone marrow hematopoiesis recovered by such types, as erythroid, granulocyte, gran ulocyte whith monocytes, and uniform, when the cells number of all branches was within a normal quantity. At the phase ІІ of ChT the number of patients with hematopoiesis recovery by erythroid type decreased and number of chil dren with activation of granulocyte branch of hematopoiesis increased. In children with pro B ALL the number of erythroid elements was higher than normative at both ChT phases. A direct correlation was established between the number of myelokaryocytes (Mkc) and megakaryocytes (Mgkc) in both phase І and phase ІІ of treatment (Rs = +0.72; Rs = +0.56, respectively). There was no correlation between the radiation dose in patients (3.73 ± 0.12 mSv) and studied parameters. CONCLUSIONS Types of bone marrow recovery were established in ALL patients after the ChT indicating to the differ ent kinetic pathways of hematopoietic progenitor cells. Evaluation of reasons of prevalence of some hematopoietic branches will allow to reveal their role in leukemogenesis and to correct the treatment programs.

OBJECTIVE Identification of impact of radiation and non radiation environmental factors on development of hematopoi etic abnormalities in children and justification of criteria for the increased risk groups of hematologic diseases. MATERIALS AND METHODS The results of clinical and hematological survey of 1465 children living in Kyiv, Zhytomyr and Chernihiv regions for the period from 2008 to 2014 were presented. There were 777 children with anemia, 466 with changes in hemogram, 191 with acute leukemia. The irradiation doses, correlation of integrated pollution degree of territories with hematopoietic parameters and course hematologic diseases were estimated. Metal con tent in hair, nails, and blood was determined in 121 children. RESULTS We have found the most common cause of anemia in children and peculiarities of acute leukemia depend ing on the area integrated contamination. Number of children living in contaminated areas with pro B ALL and T ALL having an initial leukocytosis and unfavorable course of the disease was higher compared to the number of patients from moderately polluted regions (r = 0.47). There is a direct correlation between percentage of children with monocytosis and degree of territory contamination: the 20.2 % of such children lived in the intensively polluted areas and 10,3 % in moderately contaminated ones (p < 0.05). Content of Pb, Cu, Cr, Mn, Zn in biological tissues did not exceed the permissible MAC. Level of Zn in all children was at the lower normal threshold. Individual levels of metals in hair, nails and blood did not depend on gender of patients and their radiation doses. Criteria of increased risk of hematologic diseases in children living in ecologically unfavorable regions were grounded. CONCLUSIONS Radiation and non radiation environmental factors influencing the development of changes in hematopoiesis and characteristics of the blood system diseases in children play a role in leukeima development processes. These findings are the basis for a further research in the field of radiobiology and ecology.

Determine of the influence of adverse environmental factors, including irradiation, on the survival ofchildren with acute leukemia in the long-term period after the Chornobyl accident (2008-2017).Examined 74 children with acute leukemia (АL): 64 with acute lymphoblastic leukemia(ALL); 10 - acute myeloblastic leukemia (AML). The influence of negative environmental factors was assessed bythe degree of integrated pollution of the atmospheric air, surface waters and soils with pesticides, heavy metals (Pb,Cu, Ni, Cr, Mn, Zn, Fe) and cesium isotope 137Cs. These regions were ranked on a moderately polluted (1), polluted (2),very (3) and extremely (4) polluted territories. Took into account the age of children, blood test, immunophenotyp-ic of variant the acute leukemia, survival of patients and place of residence (city / village), serum ferritin level (SF).Exposure doses of children were in the range from 0.4 mSv to 35.0 mSv (average values were (4.25 ± 0.63 mSv)and did not affect the prognosis and variants of AL. 52 children lived in moderately and polluted territories (30 wereresidents of cities, 22 - villages). 22 patients were lived in very and extremely polluted territories (4 were residentsof cities, 18 - villages). Of 74 patients with ALL and AML 24 children died (32.4 %). The smallest number ofchildren, who died, were patients with «general type» В-ALL (18.7 %), most of all children with pro-В-ALL (8 out of10) and Т-ALL (3 of 4). Of the 52 patients, the inhabitants of moderately and polluted regions, 13 patients died (25%), while out of 22 patients, who lived in very and extremely polluted areas, 11 children died (50 % share)(rs = 0.39; p0.05). Of the 10 patients with AML, 4 children died. Most often, children died, who were residents ofvillages. Moreover, the level of SF was significantly higher in children over 6 years, the inhabitants of villages -(406.8 ± 40.6) ng/ml, compared to younger patients - (211.2 ± 32.1) ng/ml) and residents of of cities: up to 6years - (297.4 ± 52.3) ng/ml; over 6 years - (275.6 ± 29.8) ng/ml.The obtained data testify to the negative influence of environmental factors, including iron, and canbe the basis for understanding the mechanisms of potentiating influence of metals and their compounds on thedevelopment of malignant diseases of the blood system in children.Meta. Vyznachennia vplyvu nespryiatlyvykh chynnykiv dovkillia, v tomu chysli ĭ oprominennia, na vyzhyvanist' diteĭ,khvorykh na gostri leĭkemiï, u viddalenyĭ period pislia avariï na ChAES (2008-2017 rr.).Materialy i metody. Obstezheno 74 dytyny z gostrymy leĭkemiiamy (GL) (64 – z gostrymy limfoblastnymy leĭ-kemiiamy (GLL)); 10 – z gostrymy miieloblastnymy leĭkemiiamy (GML). Vplyv negatyvnykh chynnykiv navkolyshn'o-go seredovyshcha otsiniuvaly za stupenem integral'nogo zabrudnennia atmosfernogo povitria, poverkhnevykh vod iґruntiv pestytsydamy, vazhkymy metalamy (Pb, Cu, Ni, Cr, Mn, Zn, Fe) ta izotopom tseziiu 137Cs. Tsi regiony ranzhyru-valy na pomirno zabrudnenu (1), zabrudnenu (2), duzhe (3) ta nadzvychaĭno (4) zabrudnenu terytoriiu. Vrakhovu-valy vik diteĭ, pokaznyky krovi, imunofenotypovyĭ variant gostrykh leĭkemiĭ, vyzhyvanist' khvorykh i mistse pro-zhyvannia (misto/selo), riven' syrovatkovogo ferytynu (SF).Rezul'taty. Dozy oprominennia diteĭ z GL znakhodylys' v mezhakh vid 0,4 mZv do 35,0 mZv (seredni velychyny –(4,25 -#177; 0,63) mZv) i vony ne vplyvaly na prognoz perebigu ta varianty GL. 52 dytyny prozhyvaly na pomirno i za-brudnenykh terytoriiakh (30 buly zhyteliamy mist, 22 – sil). 22 khvorykh meshkaly na duzhe ta nadzvychaĭno zabrudne-nykh terytoriiakh (4 buly zhyteliamy mist, 18 – sil). Z 74 khvorykh na GLL ta GML pomerlo 24 dytyny (32,4 %). Naĭ-menshe chyslo diteĭ, iaki pomerly, buly khvorymy na «zagal'nyĭ typ» V-GLL (18,7 %), naĭbil'she – dity z pro-V-GLL(8 z 10) ta T-GLL (3 z 4). Sered 52 khvorykh, zhyteliv pomirno ta zabrudnenykh regioniv, pomerlo 13 patsiientiv (do-lia – 25 %), todi iak z 22 khvorykh, iaki zhyly na duzhe ta nadzvychaĭno zabrudnenykh terytoriiakh, pomerlo 11 diteĭ (do-lia – 50 %) (rs = 0,39; p -#060; 0,05). Sered 10 khvorykh na GML pomerlo 4 dytyny. Chastishe pomyraly dity, iaki buly zhy-teliamy sil. Prychomu, riven' SF buv dostovirno vyshchyĭ u diteĭ starshykh za 6 rokiv, zhyteliv sil – (406,8 -#177; 40,6) ng/ml,porivniano z khvorymy molodshogo viku – (211,2 -#177;32,1) ng/ml i zhyteliv mist: do 6 rokiv – (297,4-#177;52,3) ng/ml;starshi za 6 rokiv – (275,6 -#177; 29,8) ng/ml.Vysnovky. Otrymani dani svidchat' pro negatyvnyĭ vplyv chynnykiv dovkillia, v tomu chysli ĭ zaliza, i mozhut' bu-ty pidґruntiam dlia rozuminnia mekhanizmiv potentsiuiuchogo vplyvu metaliv ta ïkh spoluk na rozvytok zloiakisnykh zakh-voriuvan' systemy krovi u diteĭ.

OBJECTIVE To investigate the aminoacid composition in the stromal fibroblasts of bone marrow and indexes of hemogram in children with acute lymphoblastic leukemias, which exposed to radiation from the Chornobyl accident, for evaluation of the median survival. MATERIALS AND METHODS In the study 54 patients with acute lymphoblastic leukemia, residents of Kyiv, Zhytomyr and Chernihiv regions of Ukraine were involved. Effectiveness of stromal fibroblasts colony forming units of bone marrow and aminoacid composition of fibroblasts were studied. Bone marrow examination was conducted on day33 and after stop of chemotherapy, the median survival of patients and exposure dose were evaluated. RESULTS In children with acute leukemias effectiveness of stromal fibroblasts of bone marrow was 2-2,3 times lower than normative. Correlation (rs = +0,83) between the number of erythroid progenitor cells in the bone marrow and proline content in stromal fibroblasts established . The correlation between patients median survival and number of granulocytes in myelogram (rs = + 0,82) was proven. Mean exposure doses in patients was (5,86 ± 1,11) mSv and it did not correlate with myelogram results, effectiveness of stromal fibroblasts of bone marrow and median survival. CONCLUSIONS The median survival of patients with acute leukemias depends on the content of amino acids in stro mal fibroblasts of bone marrow and recover of hematopoiesis after chemotherapy.

Determination of serum cortisol level in the initial period of acute leukemia in children, who exposed to ion izing radiation and other factors of Chornobyl accident, depending on their age and prognosis of disease.The study involved 283 children residents of Kyiv, Zhytomyr and Chernihiv regions. There were 90 acute leukemia patients(AL) (ALL - 56, AML - 34), and 193 people of comparison group with anemia, leukemoid reactions and lymphadenopathy. We analyzed the type of comorbid somatic pathology, diseases in the genealogy, hematological parameters, cortisol levels in blood serum and irradiation doses in all children. In patients with AL expected median survival was calculated.In 28.9 % of AL children the initial cortisol content was below 200 nmol/l, in 7.8 % - higher than 500 nmol/l (in the comparison group 10.4 % and 17.1 % respectively). Among AL patients with cortisol levels below 200 nmol/l were significantly less amount of persons with chronic bacterial infections and persistent viral infections (CMV, EBV) and in the genealogy of these children allergic reactions, endocrine pathology diagnosed more often compared with patients, whose hormone levels was higher than 200 nmol/l (p0.05). Distribution of children from control group by gradations of cortisol, age groups, defined somatic pathology and diseases in genealogy had no difference. It is shown, that lower initial blood serum cortisol level in ALL children correlates to a greater probability of relapse (Rs = -0,67). In patients with AML a direct correlation between cortisol level and median survival was detected (Rs = 0,79). Children radiation doses were ranging from 0.08 mSv to 14.9 mSv, and there were slightly higher among residents of Zhytomyr region (8.4 ± 1.2 mSv) compared to other regions. However, these doses did not affect blood serum cortisol levels in children and the course of AL.These data suggest the need for correction and individualization of corticosteroid doses for optimization of AL patients treatment. Children, who have lower than normative serum cortisol levels are at increased risk of hema tologic pathology and they need for hematologic monitoring.Meta. Vyznachennia rivniv kortyzolu syrovatky krovi v initsial'nyy̆ period gostrykh ley̆kemiy̆ u ditey̆, iaki zaznaly vplyvu ionizuiuchogo vyprominiuvannia ta inshykh chynnykiv avariï na ChAES, zalezhno vid viku i prognozu perebigu zakh voriuvannia.Materialy i metody. Obstezheno 283 dytyny, zhyteliv Kyïvs'koï, Zhytomyrs'koï ta Chernigivs'koï oblastey̆. Z gostroiu ley̆kemiieiu (GL) bulo 90 khvorykh (gostroiu limfoblastnoiu ley̆kemiieiu – 56, gostroiu miieloblastnoiu ley̆ kemiieiu – 34), 193 osoby z anemiiamy, ley̆kemoïdnymy reaktsiiamy i limfadenopatiiamy sklaly grupu porivniannia. U vsikh ditey̆ analizuvaly vyd komorbidnoï somatychnoï patologiï, zakhvoriuvannia v rodovodi, gematologichni pokaznyky, riven' kortyzolu v syrovattsi krovi ta dozy oprominennia. U khvorykh na GL rozrakhovuvaly medianu vyzhyvanosti. Rezul'taty. U 28,9 % ditey̆ z GL initsial'nyy̆ vmist kortyzolu buv nyzhchyy̆ za 200 nmol'/l, u 7,8 % – vyshchyy̆ za 500 nmol'/l (v grupi porivniannia 10,4 ta 17,1 %, vidpovidno). Sered khvorykh na GL z rivnem kortyzolu nyzhchym za 200 nmol'/l bulo dostovirno menshe osib z khronichnymy bakterial'nymy infektsiiamy ta persystuiuchymy virusnymy infektsiiamy (tsytomegalovirus, virus Epshtey̆na Barr) i u rodovodi tsykh ditey̆ chastishe diagnostuvalys' alergichni reaktsiï ta endokrynna patologiia, porivniano z khvorymy, u iakykh riven' gormonu perevyshchuvav 200 nmol'/l (r0,05). Rozpodil ditey̆ grupy porivniannia za gradatsiiamy kortyzolu, vikovymy grupamy, vyznachenoiu somatychnoiu patologiieiu i khvorobamy u rodovodi riznytsi ne mav. Pokazano, shcho nyzhchyy̆ riven' initsial'nogo kortyzolu v syro vattsi krovi ditey̆ z gostrymy limfoblastnymy ley̆kemiiamy koreliuie z bil'shoiu virogidnistiu rozvytku retsydyvu zakhvoriuvannia (Rs = –0,67). U khvorykh na gostru miieloblastnu ley̆kemiiu vstanovlena priama koreliatsiy̆na za lezhnist' mizh rivnem kortyzolu i medianoiu vyzhyvanosti (Rs = 0,79). Dozy oprominennia ditey̆ znakhodylysia v me zhakh vid 0,08 do 14,9 mZv, i buly deshcho vyshchymy u zhyteliv Zhytomyrs'koï oblasti (8,4 ± 1,2 mZv) porivniano z inshy my regionamy. Odnak zaznacheni dozy ne vplyvaly na riven' kortyzolu v syrovattsi krovi u ditey̆ ta perebig GL. Vysnovky. Otrymani dani svidchat' pro neobkhidnist' korektsiï ta indyvidualizatsiï doz kortykosteroïdnykh prepa rativ u khvorykh na GL z metoiu optymizatsiï likuvannia. Dity, u iakykh riven' syrovatkovogo kortyzolu nyzhchyy̆ za nor matyvnyy̆, stanovliat' grupu pidvyshchenogo ryzyku z onkogematologichnoï patologiï i potrebuiut' gematologichnogo monitoruvannia.

Evaluation of proliferation and differentiation processes of progenitor cells in bone marrow by the com position of elements of erythroid, granulocyte and platelet branches of hematopoiesis on the treatment stages in children with acute lymphoblastic leukemia (ALL), who were exposed to radiation from the Chornobyl NPP accident.The 46 children with ALL were studied, who lived in Kyiv, Zhytomyr and Chernihiv regions. Studies were conducted before the start of chemotherapy (ChT), on the 33 day of ChT (phase I), and after the com pletion of ChT (phase II). Exposure doses of patients, hemogram and myelogram parameters both with indices of mat uration of progenitor cells were evaluated. Signs of dysplasia of hematopoietic branch elements were revewed.The 46 patients were studied. They have had the B ALL, namely pro B ALL (n=5), «common type» (n=36), pre B ALL (n=3), and T ALL in 2 other cases. In a debut of ALL the bone marrow was represented by lymphoblasts. Along with ChT conduction the bone marrow hematopoiesis recovered by such types, as erythroid, granulocyte, gran ulocyte whith monocytes, and uniform, when the cells number of all branches was within a normal quantity. At the phase ІІ of ChT the number of patients with hematopoiesis recovery by erythroid type decreased and number of chil dren with activation of granulocyte branch of hematopoiesis increased. In children with pro B ALL the number of erythroid elements was higher than normative at both ChT phases. A direct correlation was established between the number of myelokaryocytes (Mkc) and megakaryocytes (Mgkc) in both phase І and phase ІІ of treatment (Rs = +0.72; Rs = +0.56, respectively). There was no correlation between the radiation dose in patients (3.73 ± 0.12 mSv) and studied parameters.Types of bone marrow recovery were established in ALL patients after the ChT indicating to the differ ent kinetic pathways of hematopoietic progenitor cells. Evaluation of reasons of prevalence of some hematopoietic branches will allow to reveal their role in leukemogenesis and to correct the treatment programs.Meta. Vyvchyty protsesy proliferatsiï ta dyferentsiiuvannia klityn poperednykiv kistkovogo mozku za skladom elementiv erytroïdnoï, granulotsytarnoï ta trombotsytarnoï lanok gemopoezu na etapakh likuvannia ditey̆ z gostry my limfoblastnymy ley̆kemiiamy (GLL), iaki zaznaly vplyvu ionizuiuchogo vyprominiuvannia vnaslidok avariï na Chornobyl's'kiy̆ AES.Materialy i metody. Obstezheno 46 ditey̆, khvorykh na GLL, iaki prozhyvaly na terytoriiakh Kyïvs'koï, Zhytomyrs'koï ta Chernigivs'koï oblastey̆. Doslidzhennia provedeni pered pochatkom khimioterapiï (KhT), na 33 y̆ den' KhT (I etap) ta pislia zakinchennia kursu KhT (II etap). Otsiniuvaly dozy oprominennia khvorykh, pokaznyky gemogram i miielogram ta indeksy dozrivannia klityn poperednykiv. Analizuvaly oznaky dysplaziï elementiv lanok gemopoezu Rezul'taty. Obstezheno 46 khvorykh na V GLL (5 – pro V GLL, 36 – «zagal'nyy̆ typ», 3 – pre V GLL) ta 2 dytyny z T GLL. V debiuti GLL kistkovyy̆ mozok u khvorykh buv predstavlenyy̆ limfoblastamy. Pry provedenni KhT kistko vomozkove krovotvorennia vidnovliuvalos' za takymy typamy: erytroïdnym, granulotsytarnym, granulotsytar nym z monotsytamy ta rivnomirnym, koly chyslo klityn vsikh parostkiv bulo v mezhakh normatyvnykh velychyn. Na II etapi KhT zmenshuvalos' chyslo khvorykh, u iakykh vidnovlennia krovotvorennia vidbuvalosia za erytroïdnym typom ta zbil'shuvalos' chyslo ditey̆ z aktyvatsiieiu granulotsytarnoï lanky gemopoezu. Za naiavnosti u ditey̆ pro V GLL na obokh etapakh KhT erytroïdni elementy buly vyshchymy za normatyvni. Priamyy̆ koreliatsiy̆nyy̆ zv'iazok vstanovlenyy̆ mizh chyslom miielokariotsytiv ta megakariotsytiv na I ta II etapakh likuvannia (Rs = +0,72; Rs = +0,56, vidpovidno). Koreliatsiy̆nogo zv’iazku mizh dozamy oprominennia khvorykh (3,73 ± 0,12 mZv) i vyznachenymy parametramy vstanov leno ne bulo.Vysnovky. Vstanovleni typy vidnovlennia kistkovogo mozku u khvorykh na GLL pislia KhT svidchat' pro rizni me khanizmy kinetyky klityn poperednykiv gemopoezu. Vyvchennia prychyn prevaliuvannia okremykh lanok krovotvo rennia u khvorykh nadast' zmogu rozkryty ïkh rol' v ley̆kemogenezi ta koryguvaty programy terapiï.

Identification of impact of radiation and non radiation environmental factors on development of hematopoi etic abnormalities in children and justification of criteria for the increased risk groups of hematologic diseases.The results of clinical and hematological survey of 1465 children living in Kyiv, Zhytomyr and Chernihiv regions for the period from 2008 to 2014 were presented. There were 777 children with anemia, 466 with changes in hemogram, 191 with acute leukemia. The irradiation doses, correlation of integrated pollution degree of territories with hematopoietic parameters and course hematologic diseases were estimated. Metal con tent in hair, nails, and blood was determined in 121 children.We have found the most common cause of anemia in children and peculiarities of acute leukemia depend ing on the area integrated contamination. Number of children living in contaminated areas with pro B ALL and T ALL having an initial leukocytosis and unfavorable course of the disease was higher compared to the number of patients from moderately polluted regions (r = 0.47). There is a direct correlation between percentage of children with monocytosis and degree of territory contamination: the 20.2 % of such children lived in the intensively polluted areas and 10,3 % in moderately contaminated ones (p0.05). Content of Pb, Cu, Cr, Mn, Zn in biological tissues did not exceed the permissible MAC. Level of Zn in all children was at the lower normal threshold. Individual levels of metals in hair, nails and blood did not depend on gender of patients and their radiation doses. Criteria of increased risk of hematologic diseases in children living in ecologically unfavorable regions were grounded.Radiation and non radiation environmental factors influencing the development of changes in hematopoiesis and characteristics of the blood system diseases in children play a role in leukeima development processes. These findings are the basis for a further research in the field of radiobiology and ecology.Meta. Vyznachyty vplyv radiatsiy̆nykh ta neradiatsiy̆nykh chynnykiv dovkillia na rozvytok zmin v gemopoezi u ditey̆ ta obґruntuvaty kryteriï formuvannia grupy pidvyshchenogo ryzyku rozvytku gematologichnoï patologiï.Materialy i metody. Predstavleni rezul'taty kliniko gematologichnogo obstezhennia 1465 ditey̆, zhyteliv Kyïvs' koï, Zhytomyrs'koï ta Chernigivs'koï oblastey̆ za period z 2008 r. po 2014 r. Z nykh: 777 ditey̆ z anemiiamy, 466 – zi zminamy v gemogramakh, 191 – z gostrymy ley̆kemiiamy. Otsiniuvaly dozy oprominennia ditey̆, zv’iazok stupenia integ ral'nogo zabrudnennia terytoriy̆ z pokaznykamy gemopoezu ta perebigom gematologichnoï patologiï. U 121 dytyny vyznachaly vmist metaliv u volossi, nigtiakh i krovi.Rezul'taty. Vstanovleni nay̆bil'sh chasti prychyny rozvytku anemiy̆ u ditey̆, osoblyvosti perebigu gostrykh ley̆ kemiy̆ zalezhno vid stupenia integral'nogo zabrudnennia terytoriï. Dolia ditey̆, zhyteliv duzhe zabrudnenykh tery toriy̆ z pro V GLL ta T GLL z initsial'nym ley̆kotsytozom ta nespryiatlyvym perebigom zakhvoriuvannia, bula bil' shoiu porivniano z doleiu khvorykh pomirno zabrudnenykh regioniv (r = –0,47). Vstanovlenyy̆ priamyy̆ koreliatsiy̆nyy̆ zv’iazok mizh vidsotkom ditey̆ z monotsytozamy ta stupenem zabrudnennia terytoriï: na duzhe zabrudnenykh tery toriiakh prozhyvalo 20,2 % takykh ditey̆, na pomirno zabrudnenykh – 10,3 % (r0,05). Vmist Pb, Cu, Cr, Mn, Zn u biologichnykh tkanynakh ditey̆ ne perevyshchuvav dopustymi vidnosno GDK. Riven' Zn v usikh ditey̆ znakhodyvsia na nyzhniy̆ mezhi normatyvnogo. Indyvidual'ni rivni metaliv u volossi, nigtiakh ta krovi ne zalezhaly vid stati khvorykh ta dozy oprominennia. Obgruntovani kryteriï formuvannia grupy pidvyshchenogo ryzyku rozvytku onkogemato logichnoï patologiï u ditey̆, iaki prozhyvaiut' v ekologichno nespryiatlyvykh regionakh.Vysnovky. Radiatsiy̆ni ta neradiatsiy̆ni chynnyky dovkillia vplyvaiut' na rozvytok zmin v gemopoezi ta osoblyvosti perebigu zakhvoriuvan' systemy krovi u ditey̆, vony vidigraiut' rol' v mekhanizmakh ley̆kozogenezu. Otrymani dani ie pidґruntiam dlia podal'shykh doslidzhen' u sferi radiobiologiï ta ekologiï.

Age and sexual indexies of densitometry at patients with acute leukemia (AL) and healthy children are presented. 31% of children with AL during the initial period of disease had manifestations of the osteopenic syndrome. At patients with AL more often than at healthy children anomalies of development of front part of skull are defined. The partial contribution of free and peptides-connencted oxyproline in urine at AL patients differs in comparison with control group that is caused by modification or deficiency of the corresponding enzymes. 30% of patients with AL had raised concentration of free oxyproline in urine, and lowered glycine concentration that testifies to the increased disintegration of collagen and deficiency of tile plastic material necessary for collagene-forming processes. The obtained data should be considered for forming of risk group on oncohematological pathology at children.

Objective. To justify and evaluate the effectiveness of treatment and preventive measures taken to correct the bio-chemical and biophysical changes in the structure of bone in children exposed to ionizing radiation due to Chornobyl accident in the dynamics of leukemic process. Materials and methods. The study involved 144 patients with acute lymphoid and myeloid leukemia. Serum calcium, total protein, alkaline phosphatase, cortisol and thyroid-stimulating hormone were investigated, as well as calcium and phosphate excretion, amino acids composition in the urine, acid-base balance and buffer systems of blood, bone density. Results. A reduction of bone densitometry, calcium and cortisol levels and increase of serum alkaline phosphatase and urine oxyproline were found in children with acute leukemia in acute I phase and during the chemotherapy. In the period of remission the majority of patients did not differ from the comparison group. The signs of osteopenic syndrome that require monitoring of the bone structure status were revealed in 10.0 % of children of the comparison group. Radiation doses of leukemia patients were 3.66 ± 0.11 mSv. No relationship between radiation dose and indicators that reflect the state of the bone tissue structures has been established. The use of complex health care measures in children with acute leukemia in remission, contributed to the positive effect of 62.0 %. Worser effect was observed in patients with an unfavorable course of the disease. Conclusions. Results of the study of bone tissue metabolism prove fore a change in the organic and mineral matrix in patients with acute leukemia exposed to ionizing radiation as a result of the Chonobyl NPP accident, and persons without hematologic diseases, and the need for treatment and prevention.Meta. Obg'runtuvaty ta ocinyty efektyvnist' likuval'no-profilaktychnyh zahodiv, zastosovanyh dlja korekcii' biohimichnyh i biofizychnyh zmin v strukturi kistkovoi' tkanyny u ditej, jaki zaznaly vplyvu ionizujuchogo oprominennja vnaslidok avarii' na ChAES, v dynamici lejkemichnogo procesu. Materialy i metody. Obstezheno 144 ditej, hvoryh na gostri limfota mijeloblastni lejkemii'. Doslidzhuvaly dozy oprominennja hvoryh, vmist kal'ciju, zagal'nogo bilku, luzhnoi' fosfatazy, kortyzolu i tyreotropnogo gormonu gipofizu v syrovatci krovi, kyslotno-luzhnu rivnovagu, ekskreciju fosfativ kal'ciju, sklad aminokyslot v sechi, shhil'nist' kistkovoi' tkanyny. Rezul'taty. U ditej z gostrymy lejkemijamy v I gostryj period ta pry provedenni himioterapii' vyjavleno znyzhennja pokaznyka densytometrii' kistok, rivnja kal'ciju, kortyzolu ta pidvyshhennja luzhnoi' fosfatazy v syrovatci krovi i oksyprolinu v sechi. V period remisii' zahvorjuvannja u bil'shosti hvoryh pokaznyky ne rozriznjalys' z grupoju porivnjannja. U 10,0 % ditej grupy porivnjannja vidmichajut'sja projavy osteopenichnogo syndromu. Dozy oprominennja hvoryh na gostri lejkemii' stanovyly 3,66 ± 0,11 mZv. Ne vstanovleno zv'jazku mizh dozamy oprominennja ta pokaznykamy, jaki harakteryzujut' stan struktury kistkovoi' tkanyny, i medianoju vyzhyvanosti hvoryh. Zastosuvannja kompleksu likuval'no-profilaktychnyh zahodiv u ditej, hvoryh na gostri lejkemii' v period remisii', spryjalo pozytyvnomu efektu u 62,0 %. Girshyj efekt sposterigavsja u pacijentiv z nespryjatlyvym perebigom zahvorjuvannja. Vysnovky. Rezul'taty doslidzhennja pokaznykiv metabolizmu kistkovoi' tkanyny svidchat' pro najavnist' zmin v organichnomu ta mineral'nomu matryksi jak u hvoryh na gostri lejkemii', jaki zaznajut' vplyvu ionizujuchogo oprominennja vnaslidok avarii' na ChAES, tak i osib bez onkogematologichnoi' patologii', ta neobhidnist' zastosuvannja likuval'no-profilaktychnyh zahodiv.

The objective was to study the immunogenetic component contribution to the formation of post-radiation effects in the long-term period after radiation exposure at the level of the human immune response as a prognostic criterion for risk assessment of radiation-associated somatic diseases. Study object was the convalescents of acute radiation syndrome (ARS) of the first grade of severity, 88 patients with a similar radiation history but with unconfirmed ARS, 73 patients being the liquidators of the Chornobyl accident consequences (LCAC) with chronic ischemic heart disease (HIHD), 65 patients LCAC without HIHD, 120 non-exposed patients with HIHD, 256 patients with oncohematological diseases and 500 healthy people - a population control.Markers of risk of realization of genetic predisposition to oncohematological and cardiovascular disease in these groups were identified on the basis of study of immunological, hematological and molecular genetic disorders in relation to immunogenetic factors.These data indicate that realization of HLA-genetic predisposition to the disease is one of the radiation associated multifactorial pathology pathways, and presence of radiosensitivity markers in pheno/genotype enhances the realization risk of pathological process under irradiation.Meta roboty poljagala u vyvchenni vnesku imunogenetychnoi' komponenty v formuvannja postradiacijnyh efektiv u viddalenomu periodi pislja oprominennja na rivni imunnogo reaguvannja organizmu ljudyny, jak prognostychnogo kryteriju ocinky ryzyku realizacii' radiacijno-asocijovanoi' somatychnoi' patologii'. Ob’jektom doslidzhennja buly rekonvalescenty gostroi' promenevoi' hvoroby (GPH) I stupenja tjazhkosti i 88 pacijentiv z analogichnym radiacijnym anamnezom, ale z nepidtverdzhenym diagnozom GPH, 73 pacijenty, jaki majut' status uchasnykiv likvidacii' naslidkiv Chornobyl's'koi' katastrofy (ULNChK) z hronichnoju ishemichnoju hvoroboju sercja (HIHS), 65 pacijentiv – ULNChK bez HIHS, 120 neoprominenyh pacijentiv z HIHS. Pacijenty z onkogematologichnoju patologijeju – 256 osib. 500 praktychno zdorovyh osib – populjacijnyj kontrol'. Rezul'taty. Na osnovi vyvchennja spektru imunologichnyh, gematologichnyh ta molekuljarno-genetychnyh porushen' u spivvidnoshenni z imunogenetychnymy chynnykamy vyznacheni markery ryzyku realizacii' genetychnoi' shyl'nosti do onkogematologichnoi' ta sercevo-sudynnoi' patologii' u zaznachenyh kontyngentiv. Vysnovky. Otrymani dani svidchat' pro te, shho odnym iz mehanizmiv formuvannja radiacijno-asocijovanoi' mul'tyfaktorial'noi' patologii', je realizacija HLA-genetychnoi' shyl'nosti do zahvorjuvannja, jak na rivni rozladiv u gemopoezi ta imunopoezi, tak i na rivni zahvorjuvannja v cilomu, a nosijstvo v feno/genotypi markeriv radiochutlyvosti pidvyshhuje ryzyk realizacii' patologichnogo procesu v umovah oprominennja.

To establish the sources of lymphocytosis in children living in ecologically unfavorable conditions after the Chornobyl Nuclear Power Plant accident aiming the high risk group formation for oncohematological diseases among the children's population.The 226 children with lymphocytosis were surveyed. The of child's life history and kind of somatic morbidity were considered. Quantitative and qualitative parameters of blood cells, biochemical indices including immunoglobulins (A, M, G), circulating immune complexes, phagocytosis indices were assayed.Children with lymphocytosis were more often born with a high bodyweight, they demonstrated manifestations of constitutional lymphatism, lymphadenopathy and more often had respiratory infections. Quantitative and qualitative changes of hemopoietic elements depended on a type of a disease. Activation of lipid peroxidation, dysimmunoglobulinemia and increased level of circulating immune complexes were revealed. Treatment and preventive actions promoted normalization of hemogram indices in 58% of children surveyed.The abnormalities in immune indices, activated lipid peroxidation in membranes of hemopoietic elements, and manifestations of granulocytopoietic disorders were established it children with lymphocytosis. Therefore these children can be attributed tot the group of increased risk on oncohematological disease.Meta – vstanovyty prychyny rozvytku limfocytozu u ditej, jaki prozhyvajut' v ekologichno nespryjatlyvyh umovah pislja avarii' na ChAES, dlja formuvannja grupy pidvyshhenogo ryzyku z onkogematologichnoi' patologii' sered dytjachogo naselennja. Materialy i metody. Obstezheno 226 ditej z limfocytozom. Vrahovuvaly anamnez zhyttja dytyny, harakter somatychnoi' patologii'. Vyvchaly kil'kisni ta jakisni parametry elementiv gemopoezu, biohimichni pokaznyky, imunoglobuliny (A, M, G), cyrkuljujuchi imunni kompleksy, pokaznyky fagocytozu. Rezul'taty. Dity z limfocytozom chastishe narodzhuvalys' z bil'shoju masoju tila, maly projavy konstytucijnogo limfatyzmu, limfadenopatiju ta chastishe hvorily na respiratorni infekcii'. Kil'kisni ta jakisni zminy v elementah gemopoezu zalezhaly vid vydu patologii'. Vyjavleno aktyvaciju procesiv perekysnogo okyslennja lipidiv, dysimunoglobulinemiju ta pidvyshhennja vysokomolekuljarnyh cyrkuljujuchyh imunnyh kompleksiv. Likuval'no-profilaktychni zahody spryjaly normalizacii' pokaznykiv gemogramy u 58% osib. Vysnovky. U ditej z limfocytozom vstanovleni zminy v pokaznykah imunitetu, procesah perekysnogo okysnennja lipidiv membran elementiv gemopoezu, projavy dyzgranulocytopoezu, shho svidchyt' pro prychetnist' cyh ditej do grupy pidvyshhenogo ryzyku z onkogematologichnoi' patologii'.

To study the serum ferritin levels in children with acute leukemia, depending on the number of transfusions of RBC concentrate and period of disease.We studied the red blood count, serum iron and ferritin levels in 54 patients with acute leukemia before chemotherapy, at the time of a standardized treatment protocol, and after transfusions of RBC concentrates.In the debute of acute leukemia just before treatment lauch the serum ferritin in 81.5% of children was 2.3-2.5 higher than normal. The need for transfusion of RBC concentrates was higher under serum ferritin level exceeding 500 ng/mL. The association was established between ferritin content and age of the children, variant of acute leukemia and period of the disease.The level of serum ferritin can be used as a marker of ferrokinetic status for timely diagnosis of iron overload in children with acute leukemias and for application of treatment-and-prophylactic actions.Meta – vyvchyty vmist syrovatkovogo ferytynu u ditej z gostrymy lejkemijamy zalezhno vid chysla transfuzij koncentrativ erytrocytiv krovi ta periodu zahvorjuvannja. Materialy i metody. Vyvchaly pokaznyky erytrocytarnoi' lanky krovi, vmist syrovatkovogo zaliza ta ferytynu u 54 hvoryh na gostri lejkemii' do pochatku polihimioterapii', v period provedennja standartyzovanogo protokolu likuvannja ta pislja transfuzij koncentrativ erytrocytiv krovi. Rezul'taty. V debjuti gostryh lejkemij do likuvannja u 81,5% ditej vmist ferytynu v syrovatci krovi buv v 2,3-2,5 razy vyshhe normatyvnogo. Potreba v transfuzijah koncentrativ erytrocytiv u hvoryh bula bil'shoju pry koncentracii' ferytynu v syrovatci krovi vyshhoju za 500 ng/ml. Vstanovlena zalezhnist' rivnja ferytynu vid viku ditej, variantu gostroi' lejkemii' ta periodu zahvorjuvannja. Vysnovky. Riven' syrovatkovogo ferytynu mozhe vykorystovuvatys' v jakosti markeru stanu ferokinetychnyh procesiv v organizmi dlja svojechasnoi' diagnostyky nadlyshku zaliza u ditej z gostrymy lejkemijamy ta zastosuvannja likuval'no-profilaktychnyh zahodiv.

The results of multidrug resistance determinants expression analysis on leukemic cells of 56 acute myeloid leukemia (AML) patients by immunophenotyping are presented. Of these, there were 21 persons exposed to ionizing radiation due to the Chemobyl accident with radiation-associated AML and 35 patients with spontaneous leukemia. The aim of this study was to determine if transport proteins (P-glycoprotein, LRP, and MDR1), apoptosis-related proteins (Fas, Bcl-2, Bax, p53, and Bcl-X(L)), and topoisomerase IIalpha expression in AML patients with the history of radiation exposure differed from those in spontaneous AML cases. Leukemic cells in patients with radiation-associated diseases compared to spontaneous AML more often overexpressed antiapoptotic oncoprotein Bcl-2 (12/21 vs. 6/35, p0.005) and less often demonstrated expression of Fas receptor (12/21 vs. 30/35, p0.05). Moreover, leukemic cells were simultaneously Fas negative and Bcl-2 positive in 4 out of 21 patients exposed to ionizing radiation but none of spontaneous cases had similar phenotype (p0.05). Leukemic cells in patients with radiation-associated AML compared to spontaneous cases more often were P-glycoprotein positive (12/20 vs 9/31, p0.05). P-glycoprotein overexpression significantly correlated with resistant disease in patients with radiation-associated AML (r = 0.47, p0.05), but was not a prognostic variable for the treatment outcome in terms of overall survival. Defects in pathways of drug-induced apoptosis and function of pump, that actively effluxes drugs could contribute significantly to developing drug resistance in radiation-associated AML.

The article considers the possibility of the use of current infrastructure of specialized population registers of Ukraine to study leukemia and other systemic blood diseases revealed in Chernobyl accident liquidators. Advantage and limitation of such registers in the use are discussed in the article. Ukrainian state register of people who suffered from Chernobyl accident and Ukrainian national cancer registers are the largest population registers in the country, which cover all the territory of Ukraine and contain information on each individual and may serve as source base for epidemiological studies. To solve issues on leukemia and other oncological diseases is recommended to use in complex data of specialized registers of Ukraine. It should be also taken into account necessity of using late registered cases and verifying registered diagnoses.

The results of proper investigations received under the cytogenetic examination of 225 persons (control groups, Chernobyl liquidators exposed to different radiation doses, oncogematology patients) had been summarized and analyzed. The conclusion concerning possibilities and limitations of FISH technique usage for retrospective biodosimetry of human radiation exposure has been presented.

The morphofunctional state of hemopoiesis in patients who suffered from the Chernobyl accident was investigated. The activation of proliferative activity of erythroid progenitor cells simultaneously with a decrease in the resistance of erythrocytes and an increase in the levels of methemoglobin, HbF, and an increase in the number of HbF-containing cells in peripheral blood were detected. Main trends in the development of adaptative processes in the erythron system as a response to affect of low doses of radiation were determined on cellular and molecular levels.

A total of 18 patients with acute leukemia from those exposed to radiation when they had liquidated the consequences of the accident at the Chernobyl Atomic Power Station were examined. Sixteen of them had acute myeloblast cell leukemia, one had acute lymphatic leukemia, and another one had acute promyelocytic leukemia. A complex of hematological, immunocytological, and cytochemical findings, as well as leukocytic and erythrocytic genetically determined antigen typing were used for diagnosis. Signs of severe vegetovascular dystonia was found to be followed by acute leukemia in all the patients. A relationship was established between the therapy resistance and the HLA antigen homozygosity in combination with genetically-determined low reactivity. There were no significant differences between the parameters in question and those in patients with acute leukemia who had been studied in the preaccident period.

The qualitative and quantitative parameters of hemopoiesis and immunocompetent cells were studied in 365 children in the early "iodine" and long-term periods after the accident. In accordance with primary response, a group consisting of 28 subjects with so-called "radiation injury" was distinguished. The early period was marked by unusual qualitative and quantitative hematological changes which, however, did not lead to the development of the hematological syndrome characteristic of acute radiation injury. Certain deviations that corresponded to somatic pathology were detectable at the late periods after the accident.

Immunoassays of the 1st and 2nd levels were investigated in patients with acute radiation disease 12-36 mos. after irradiation. A decrease in the level of helper/inducer T-lymphocytes, a tendency to a decrease in the number of suppressors and an increase in the number of theophylline-stimulated T-cells in patients with acute radiation disease of the 3rd degree were observed. Control of the immune status of this group of patients is recommended.

Der iva t ives of the s y m m e t r i c a l t r i az ines can act as folic acid antagonis ts [19]. The abili ty of such antagonis ts to induce " thymine s tarvat ion" has been descr ibed [12]. A typical f ea tu re of folic acid def ic iency in the body is a d is turbance of nucleic acid me tabo l i sm [18]. Folic acid antagonis ts a re c lassed as exogenous et iological f ac to r s in the development of hypoplast ic and ap las t ic anemias [3]. Toxicoa l le rg ic ( immunoaggress ive) blood d i s ea se s a re included by the authors under the same heading. Fol ic acid av i taminos is is accompanied by g loss i t i s , s tomat i t i s , u lcera t ive gas t r i t i s , and enterocol i t i s [14].

Colony- and cluster-forming ability of bone marrow cells in agar medium was studied in 6 healthy children and 13 children suffering from acute leukosis. During acute stages of the diseases colonies and clusters in agar medium consisted of granulocytic cells and their quantity depended on the safety of predecessors of bone marrow granulopoiesis. In contrast to acute lymphoblastic leucosis, acute myeloblastic leucosis is characterized by a sharp growth of cluster-forming and a less intensive growth of colony-forming ability of hemopoietic cells. The bone marrow remission is marked by the growth of diffusive and mixed colonies and clusters, consisting of granulomonocytic elements. The low level of colony- and cluster-formation in the medium at the last stage of therapy (induction of acute leukosis remission) correlated well with positive indices of treatment effectiveness. The results obtained during the cultivation of blood-forming cells in the agar medium may be also used for diagnosis and prognosis.

Ultrastructural peculiarities of stromal elements from bone marrow and endosteum in 28 children with acute leukaemia during clinical and hematological exacerbations are presented. Investigations are conducted before chemotherapy. Changes in ultrastructure of all stromal components are revealed. Of special significance are the data on variations of reticular cells and rough desorganization of fibrillar structures. Disturbances in intercellular contacts between hemopoietic cells and stromal elements are detected.

Cooperative investigations were conducted in seven Pediatric Hematologic Clinics (in Moscow, Leningrad, Kiev, Minsk and Tbilisi) to study the nature of late (after five years of remission) relapses of acute leukemia that were diagnosed in 21.6% of cases (in 80 out of 371 children) with long-term remissions. Late relapses in most patients occurred on the 6-7th year of remission. In cases when the treatment was abolished, relapses took place 1-2 years after the abolition. Extramedullary foci of leukemic lesions (CNS, sexual glands, etc.) were detected more frequently (41 children). Bone marrow lesions were recorded in 21 combined relapses were observed in 8 patients. It has been stressed that initial risk factors should be taken into consideration, and current diagnostic tests should be applied to individualize therapy at all the stages of the treatment.

An increased content of cytochemically heterogeneous A-RFC (responses to acid phosphatase and acid nonspecific esterase) in peripheral blood of children with T-ALL in comparison with non-T, non-B-ALL has been established. No correlation between A-RFC content and T-cells bearing FcG- and FcM-receptors has been revealed. It is supposed that A-RFC is a heterogeneous group of T-cells differing in the stage of maturity.