PROGNOSIS OF ACUTE LEUKEMIA DEPENDING ON THE IRON METABOLISM PARAMETERS IN CHILDREN AFTER CHORNOBYL NUCLEAR POWER PLANT ACCIDENT. / PROGNOZ PEREBIGU GOSTRYKh LEIKEMII U DITEI PISLIa AVARIÏ NA ChAES ZALEZhNO VID OBMINU ZALIZA.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: In 295 patients with ALL the following variants of leukemia were established: pro-B-ALL in 23, «common¼type 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 levels > 500 ng/ml (p < 0.05). 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. CONCLUSIONS: 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.

EFFECT OF SOMEUNFAVORABLE FACTORS OF ENVIRONMENT ON THE SURVIVAL OF CHILDREN WITH ACUTE LEUKEMIA IN A LONG6TERM PERIOD AFTER ACCIDENT ON THE CHORNOBYL NPP. / VPLYV DEIaKYKh NESPRYIaTLYVYKh ChYNNYKIV DOVKILLIa NA VYZhYVANIST' DITEI Z GOSTRYMY LEIKEMIIaMY U VIDDALENYI PERIOD PISLIa AVARIÏ NA ChORNOBYL'S'KII AES.

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 type¼ 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.

Cortisol level as risk factor for malignant hematologic pathology in children exposed to ionizing radiation after Chornobyl accident. / STAN ERYTROÏDNOÏ, GRANULOTsYTARNOÏ TA TROMBOTsYTARNOÏ LANOK GEMOPOEZU NA ETAPAKh KhIMIOTERAPIÏ U DITEY̆ Z GOSTRYMY LIMFOBLASTNYMY LEY̆KEMIIaMY, IaKI ZAZNALY VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa VNASLIDOK AVARIÏ NA ChAES.

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.

Effect of radiation and non radiation environmental factors on children hematopoietic system. / VPLYV RADIATsIY̆NYKh TA NERADIATsIY̆NYKh FAKTORIV DOVKILLIa NA STAN SYSTEMY KROVOTVORENNIa DITEY̆.

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.

Rationale treatment and preventive measures for correction of bone structure in children with acute leukemia, exposed to ionizing radiation due to the Chornobyl accident. / Ocinka likuval''no-profilaktychnyh zahodiv dlja korekcii' struktury kistkovoi' tkanyny u ditej z gostrymy lejkemijamy, jaki zaznaly vplyvu ionizujuchogo vyprominennja vnaslidok avarii' na ChAES.

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.

[DEFINITION OF INTERRELATION BETWEEN AMINOACID COMPOSITION OF URINE AND BONE TISSUE DENSITY AT CHILDREN WITH ACUTE LEUKAEMIA FOR ONCOHEMATOLOGICAL PATHOLOGY RISK GROUP FORMATION].

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.

Effect of RBC concentrate transfusions on serum ferritin content in children with acute leukaemia.

OBJECTIVE: To study the serum ferritin levels in children with acute leukemia, depending on the number of transfusions of RBC concentrate and period of disease. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Lymphocytosis in children after the Chornobyl NPP accident.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[The role of radiation and non-radiation factors in the development and progression of acute leukemia in children].

At 278 ALL and AML patients the kind of hereditary pathology in the family; clinikal-laboratory features and a course of acute leukemia and terms of longevity of children were studied. Degree of integrated pollution of territory (air, water, soil) by heavy metals and radionuclides and also the irradiation doses have been considered. Results which have been received testify about the certain contribution of genetic components and adverse factors of environment in of development of acute leukemia and their course at children. The definition of different leukemogenic factors action on the condition of hemopoietic system gives the chance to generate the abnormally high risk groups of oncological hematological pathologies among the children's population and to improve the diagnostic and treatment-and-prophylactic actions.

[State of bone structures in children with acute leukemia, experiencing unfavorable factors from Chernobyl accident].

The authors present an assessment of bone structure condition in children with acute leukemia. The changes in the collagen molecule, amino acid composition of urine and proteins reparation processes were revealed. Calcium phosphate excretion in the patients urine were increased. The serum osteocalcin level and colony formation efficiency of bone marrow fibroblasts in acute leukemia patients are lower than in control group. In the initial period of the disease 32% of patients have disturbancies in their endocrine status. The bone structure violation is combined with unfavorable disease outcome. The effectiveness of the treatment and prevention steps in acute leukemia patients depends on the leukemic process stage.