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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.

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.

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.

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.

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].