1. What is the relationship between endothelial dysfunction (ED) and pulmonary complications in children with acute lymphoblastic leukemia (ALL) during the acute phase of chemotherapy?
Endothelial dysfunction (ED) is a common feature of various early complications of chemotherapy and can influence the prognosis of leukemia despite the optimization of treatment protocols. Researchers have studied biomarkers such as selectins E and P, plasminogen activator inhibitor type 1, soluble intercellular adhesion molecule 1, soluble vascular adhesion molecule 1, and vascular endothelial growth factor (VEGF) concentrations to determine the levels of ED in children with ALL during the acute phase of chemotherapy. Increased levels of ED can be indicative of poorer short-term prognosis in children with ALL. Studies have found increased serum thrombomodulin and von Willebrand factor levels as a marker of significant endothelial dysfunction during the acute period of ALL, which can be considered as an additional prognostic factor for unfavorable outcome. ED is present not only in the acute period of leukemia but also persists in the remission period. The study of Masopustova A., Jehlicka P. et al. (2018) considers ED in ALL survivors, and significantly decreased reactive hyperemia index, elevated levels of high-sensitivity C-reactive protein, and E-selectin in plasma prove the presence of endothelial dysfunction in patients with ALL in remission at least 2 years after successful chemotherapy. The study of Sadurska E., Zaucha-Prazmo A. et al. (2018) detected increased circulatory levels of intercellular adhesion molecule 1 and mean carotid intima-media thickness in the remission period of ALL, demonstrating the presence of endothelial damage in blood vessels. Most studies of ED in leukemic survivors deal with the relationship between endothelial damage markers and a higher risk of developing cardiovascular complications. The blood-air barrier consists of an alveolar epithelium, a continuous capillary endothelium, and connective tissue. Studies have proven the presence of endothelial dysfunction in patients with respiratory distress syndrome, pneumonia, and bronchial asthma, indicating that the formation of chronic inflammation of the respiratory system is related to the functioning of the endothelial layer of the blood-air barrier. However, there is a lack of studies on the status of the blood-air barrier and its endothelial layer in leukemic children. The study of ED and its damage markers can be useful for a more detailed understanding of the development of pathological processes in the lungs and its connection with pulmonary complications in children with ALL. In this study, the levels of VEGF-A were determined to find correlation with blood-air barrier damage and potential prognostic value for the formation of pulmonary complications in children with ALL.
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2. What is the age range of children with ALL in the study?
The age range of children with ALL in the study is 6-17 years. The researchers examined 40 children, including 26 boys and 14 girls, who were diagnosed with Acute Lymphoblastic Leukemia (ALL). The children were treated in the hematological department of the Kharkiv Municipal Clinical Children's Hospital 16 in Ukraine. The inclusion criteria for the study were a verified diagnosis of ALL, age between 6-17 years, signed consent from parents, and/or patients. The exclusion criteria included relapsed or secondary ALL, diagnosed chronic pulmonary diseases, disorders of endothelial function, hereditary diseases affecting the respiratory system, and proven hereditary immune deficiency. The children were divided into two groups: newly diagnosed ALL (n=18) and ALL survivors (n=22) who had completed the total course of chemotherapy and had a remission for at least two years. The study aimed to assess the level of VEGF-A in children with ALL to understand endothelial dysfunction.
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3. How is VEGF-A assessed in serum?
VEGF-A levels in serum are assessed by collecting venous blood in the fasting state, centrifuging it, and freezing the serum samples. The enzyme-linked immunosorbent assay (ELISA) using commercial kits is then used to analyze VEGF-A levels. Statistical analysis is performed using Statistica 8, with non-parametric Mann-Whitney U-test for comparing two independent samples. Ethics approval and informed consent were obtained for the study.
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4. What is the relationship between VEGF-A levels and pulmonary complications in ALL survivors?
The study found a statistically significant increase in VEGF-A levels in children with ALL in remission, even after completing chemotherapy. There were no significant differences in VEGF-A levels between groups 1 and 2. However, among ALL survivors in group 2 with persistent pulmonary complications, children had significantly higher levels of VEGF-A. ROC-analysis showed that a VEGF-A level > 198.34 pg/ml could predict the presence of pulmonary complications in ALL survivors. The AUC was 0.965, with a sensitivity of 100% and specificity of 89.47%. The positive likelihood ratio was 9.50, and the negative likelihood ratio was 0.00. This suggests that VEGF-A levels can be used as a predictor for pulmonary complications in ALL survivors.
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