Background. Endothelial dysfunction (ED) is common in acute leukemia patients. The study of ED can provide more information about pathological processes in lungs of children with acute lymphoblastic leukemia (ALL). The purpose of the study is to assess the levels of vascular endothelial growth factor A (VEGF-A) and its prognostic value for pulmonary complications in children with ALL. Materials and methods. The control group consisted of 15 healthy children. The level of VEGF-A in serum was assessed by enzyme-linked immunosorbent assay. Results. Pulmonary complications were common in the examined children with ALL, among them: аcute bronchitis (23), recurrent episodes of acute bronchitis (5), pneumonia (18), wheezing (9), bronchial asthma (3), interstitial pneumonia (1), pleurisy (1), pneumothorax (3), lung fibrosis (2), respiratory failure (6). The frequency of pulmonary complications was 82.5 % during chemotherapy protocols and 20.0 % in ALL survivors after a complete course of chemotherapy. Statistically significant increase in VEGF-A level in groups 1 (180.41 (158.16; 200.00) pg/ml) and 2 (165.61 (131.65; 198.45) pg/ml) compared to controls (130.65 (129.45; 132.15) pg/ml) has been detected (p1-C = 0.000011; p2-C = 0.007009). There were no significant differences in VEGF-А levels between children from experimental groups (p1–2 = 0.338394). According to receiver operator characteristic (ROC) analysis, the level of VEGF-A > 198.34 pg/ml after the complete course of chemotherapy can predict the presence of pulmonary complication in ALL survivors (area under the ROC curve 0.965; sensitivity 100.00 %; specifi­city 89.47 %). Conclusions. Children with ALL have significant ED. The level of serum VEGF-A can be predictive for pulmonary complications in ALL survivors.

Objective. Monocyte chemoattractant protein-1 (MCP)-1 and soluble vascular cell adhesion molecule-1 (sVCAM-1) are key regulators of the inflammation sites infiltrated with monocytes. The aim of the study was to investigate the role of these molecules in children with asthma. Methods. The levels of MCP-1 and sVCAM-1 during asthma exacerbation on the background of therapy in children with various degrees of asthma severity as well as correlation relationships between MCP-1, sVCAM-1 and parameters of respiration function were determined. Results. The level of MCP-1 and sVCAM-1 in all groups of the examined patients at the period of exacerbation of the disease was significantly higher than in children of the control group. On the background of therapy the levels of MCP-1 and sVCAM-1were decreased in patients of all groups, regardless of asthma severity. Negative correlation relationships between MCP-1 and FEV1, PEF, VC, FVC, FEV1/FVC were revealed before and after the therapy. Conclusions. The increased levels of the abovementioned biomarkers were preserved on the seventh day of therapy. This testifies to the involvement of these chemokines into the formation and prolongation of the inflammatory process. The revealed negative correlation between MCP-1 and the main parameters of pulmonary function testified to participation of chemoattractant MCP-1 in chronic inflammation of the airways.

DISORDERS OF HAEMOSTASIS, COMPLICATIONS AND THEIR CORRECTION IN CHILDREN WITH ACUTE LEUKEMIAMakieieva N. I., Gubar S.O., Koval V. A., Zharkova T. S.Purpose. To study the significance of capillarotrophic disorders in the development of complications of chemotherapy in children with acute leukemia and the effectiveness of the treatment and prevention of these complications. Patients and methods. Parameters of haemostasis system (plasma, platelet and vascular chains) have been studied in 86 children aged 1 - 17 years with acute leukemia in the dynamics of the disease, before the start and on the background of chemotherapy during the development of infectious and non-infectious complications. The patients received standard therapy according to the BFM protocols were divided into two groups according to the difference in the substitution therapy: group 1 - patients did not receive platelet replacement therapy, group 2 - ones received replacement therapy, including preventive platelet transfusion. The effectiveness of therapy was accessed by comparing the number of complications in patients of both groups.  Results. In 100% of patients, severe myelosuppression was observed. A decrease in the number of platelets in the blood lower than 20*109/l was found to be in 43% of patients, agranulocytosis was found in 35%. Patients of the 1st group had bleeding  in 33% of cases, anemia of II-III stage of severity  in 76%, gastroenterologic inflammation  in 21%, respiratory distress syndrome in 33% , pneumonia  in 47% , sepsis  in 14%, other localization of infection in 13%. In patients of the 2nd group the incidence of complications of chemotherapy and their severity decreased in 2–6 times. The concept of the leading role of thrombocytopenia in the development of stages of capillarotrophic disorders is presented. Conclusions. The results indicate the important role of severe thrombocytopenia and capillarotrophic disorders in the occurrence of infectious and non-infectious complications of chemotherapy in patients with acute leukemia. Adequate replacement therapy with donor platelets reduces the number and severity of complications, increases the effectiveness of treatment.Key words:  acute leukemia, children,  complications, correction, haemostasis Порушення гемостазу,  ускладненнята їх корекція у хворихна гостру лейкемію дітей.Макєєва Н.І., Губар С.О., Коваль В.А., Жаркова Т.С.Мета: вивчити значимість капілляротрофічних порушень в розвитку ускладнень хіміотерапії у дітей хворих на гостру лейкеміюй ефективність лікування і профілактики цих ускладнень. Пацієнти і методи. У 86 дітей у віці 1 - 17 років хворих на гостру лейкемію вивчені показники системи гемостазу (плазмового, тромбоцитарного та судинної ланок) в динаміці захворювання, до початку і на тлі застосування хіміотерапії при розвитку інфекційних і не інфекційних ускладнень. Хворі отримували стандартну терапію за протоколами BFM були розділені на дві групи за відмінностями в терапії супроводу: 1 група - хворі не отримували замісну терапію тромбоконцентратом, 2 група - отримувала замісну терапію, в тому числі, і превентивну трансфузию тромбоцитів. Ефективність терапії оцінювали порівняням числа ускладнень у пацієнтів обох груп. Результати. У 100% хворих виявлена тяжка мієлосупресія зі зниженням числа тромбоцитів у крові нижче 20 * '10 9 / л у 43%, агранулоцитоз - у 35%. У хворих 1 групи реєстрували кровотечу - у 33%, анемію II-III ступеня тяжкості - у 76%, стоматоезофагоентероколіт - у 21%, респіраторний дистрес-синдром - у 33%, пневмонію - в 47%, сепсис - у 14%, інші локалізації інфекції – у 13% випадків. У хворих 2 групи в 2 - 6 разів зменшилася частота розвитку ускладнень хіміотерапії та їх тяжкість. Представлена концепція провідної ролі тромбоцитопенії в розвитку стадій капілляротрофічних порушень. Висновки. Отримані результати свідчать про важливу роль важкої тромбоцитопенії і капілляротрофічних порушень у виникненні інфекційних і неінфекційних ускладнень хіміотерапії у хворих на гостру лейкемію. Адекватна замісна терапія донорським тромбоконцентратом знижує число і тяжкість ускладнень, підвищує ефективність лікування.Ключові слова: гемостаз, гостра лейкемія, діти, корекція, ускладнення Нарушения гемостаза, осложнения и их коррекция у детей сострым лейкозом.Макеева Н.И., Губарь С.О., Коваль В.А., Жаркова Т.С. Цель: изучить значимость капилляротрофических нарушений в развитии осложнений химиотерапии у детей больных острым лейкозом  и эффективность лечения  и профилактики этих осложнений. Пациенты и методы. У 86 детей в возрасте 1 – 17 лет больных острым лейкозом изучены показатели системы гемостаза (плазменного, тромбоцитарного и сосудистого звеньев) в динамике заболевания, до начала  и на фоне применения химиотерапии при развитии инфекционных и не инфекционных осложнений. Больные получали стандартную терапию по протоколам BFM были разделены на две группы по различию в проводимой терапии сопровождения: 1 группа – больные не получали заместительную терапию тромбоконцентратом, 2 группа -  получала заместительную терапию, в том числе, и превентивную трансфузию тромбоцитов. Эффективность терапии оценивали сравнением числа осложнений у пациентов обеих групп.Результаты. У 100% больных выявлена тяжелая миелосупрессия со снижением числа тромбоцитов в крови ниже 20*10 9/л у 43%, агранулоцитоз – у 35%. У больных І группы регистрировали кровотечение - в 33%, анемия II-III степени тяжести - в 76%, стоматоэзофагоентероколит - в 21%,  респираторный дистресс-синдром – в 33%, пневмония – в 47%, сепсис – в 14%, иные локализации инфекции – 13% случаев.  У больных II группы  в 2 – 6 раз уменьшилась частота развития осложнений химиотерапии и их тяжесть. Представлена концепция ведущей роли тромбоцитопении в развитии стадий капилляротрофических нарушений. Выводы. Полученные результаты свидетельствуют о важной роли тяжелой тромбоцитопении и капилляротрофических нарушений в возникновении инфекционных и неинфекционных осложнений химиотерапии у больных острым лейкозом. Адекватная заместительная терапия донорским тромбоконцентратом снижает число и тяжесть осложнений, повышает эффективность лечения.Ключевые слова:  гемостаз, дети,коррекция, осложнения, острый лейкоз

Background. Damage markers of blood-air barrier are important for studding pathological process in lungs in children with acute lymphoblastic leukemia (ALL). Purpose is to analyses pulmonary complications and to assess IL-6 and TGF-β levels in the exhaled breath condensate (EBC) in children with ALL and its prognostic value. Materials and Methods. 40 children with ALL aged 6–17 years were examined. 1st group included newly diagnosed ALL (n = 18). 2nd group involved ALL survivors who had completed course of ALL IC BFM 2009 protocols (n = 22). The control group consisted of 15 healthy children. The levels of IL-6 and TGF- β in the EBC were analyzed by ELISA. Results and discussion. Pulmonary complications presented in 82.5% of children with ALL during chemotherapy and in 15.8% of ALL survivors. IL-6 and TGF-β levels in EBC were significantly higher in both ALL groups than control: IL-6 p1-C = 0,000001; p2-C = 0,000000; TGF-β p1-C = 0.000014; p2-C = 0.009364. 1st group had higher levels of IL-6 and TGF-β in the EBC than 2nd group: IL-6 p1-2 = 0,000000; TGF-β p1-2 = 0.000141. There was a positive correlation between IL-6 and TGF-β levels (r = 0.681176, p = 0.000001). According to ROC analysis, IL-6 level in EBC collected during Protocol 1 > 47.64 pg/ml can be prognostic for pulmonary complications during chemotherapy (AUC 0.875; Sensitivity 75.0%; Specificity 100,0%). Level of IL-6 > 49.96 pg/ml can predict pneumonia during chemotherapy (AUC 0,883; Sensitivity 100.00%; Specificity 81.82%). IL-6 level after the total course of chemotherapy > 23.64 pg/ml can predict pulmonary complications in ALL survivors (AUC 0.819; Sensitivity 75.00%; Specificity 81.82%). TGF-β level in EBC after the completion of chemotherapy > 19.93 pg/ml can be prognostic for pulmonary complications in ALL survivors (AUC 0.896; Sensitivity 100.00%; Specificity 77.78%). Conclusions. IL-6 and TGF-β levels in EBC can be prognostic for pulmonary complications in children with ALL.

Introduction. Pulmonary complications are common in children with acute lymphoblastic leukemia (ALL). The assessment of phospholipids (PL) in the exhaled breath condensate can provide more information about pathological processes in the lungs in children with ALL. Purpose - to assess the level of PL in the exhaled breath condensate (EBC) in children with ALL and its prognostic value. Materials and methods. 40 children with ALL aged 6-17 years were examined. 1st group included newly diagnosed children with ALL (n=18). 2nd group involved ALL survivors, who had completed the total course of chemotherapy (n=22). The control (С) group consisted of 15 healthy children. The levels of PL in the EBC were investigated by spectrophotometric thin-layer chromatography using an SPh 46 spectrophotometer. Results. The frequency of pulmonary complication was 82.5% during chemotherapy protocols and 18.4% in ALL survivals. The statistically significant increase in the level of phospholipids in 1st (150.75 (137.62; 158.45) mmol/l) and 2nd (130.12 (120.59; 138.34) mmol/l) ALL groups compared with the group C (54.80 (48.30; 60.80) mmol/l) has been detected (p1-C=0.0000; p2-C=0.0000). Children of the 1st group had significantly higher levels of PL in the EBC than children of the 2nd group (p1-2=0.002911). PL level in EBC collected during induction phase of chemotherapy >132.15 mmol/l can be prognostic for the development of acute pulmonary complications (Sensitivity 93.75%; Specificity 100%). PL level in EBC collected after a complete course of chemotherapy >133.28 mmol/l can be predictive for persistent pulmonary complications (Sensitivity 100.00%; Specificity 83.33%). Conclusions. PL level in EBC can be prognostic for the development of pulmonary complications, both during chemotherapy and in long-term remission after completed chemotherapy course. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.