Endothelial Function in Children with Acute Lymphoblastic Leukemia (ALL) May Reflect the Clinical Outcome

Abstract

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

Markers of Endothelial Dysfunction and Their Prognostic Value in Children With Acute Lymphoblastic Leukemia

“…For example, asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NO synthase and is increased in patients with ALL. ADMA is a product of tumor cell degradation, oxidative stress, manifestation of liver failure and inflammation of the endothelial wall [5,8,9]. It should be noted that there are a number of scientific studies on the levels of nitric oxide in ALL, which have shown the results of increasing total NO [7,14,15].…”

“…Reduction of biological activity of nitric oxide (NO) leads to stimulation of vasoconstriction, inflammation and thrombosis, damage to tissue structures, plays a crucial role in the pathogenesis of ED [5,8,16]. The role of nitric oxide in disorders of cardiovascular function under conditions of endotoxic shock has been proved [16].…”

“…Infectious-toxic complications are particularly severe as they are more often lethal than relapse of leukemia [4]. The survival rate of children diagnosed with ALL has been improved due to anthracycline agents, but their use is accompanied by vascular endothelial damage with subsequent development of endothelial dysfunction (ED) [5,6]. Moreover, it has been proved that ED is part of ALL phenotype in children [5,[7][8][9], which also explains the effect of anthracycline agents.…”

“…The survival rate of children diagnosed with ALL has been improved due to anthracycline agents, but their use is accompanied by vascular endothelial damage with subsequent development of endothelial dysfunction (ED) [5,6]. Moreover, it has been proved that ED is part of ALL phenotype in children [5,[7][8][9], which also explains the effect of anthracycline agents. Studies have shown that there are functional cross-links between hematologic malignancies and vascular endothelium [10].…”

“…To date, it has been proven that ED is a common feature of many early complications of chemotherapy, which are a significant cause of morbidity and mortality, despite optimization of treatment protocols [5]. However, there is insufficient data on the role of ED markers in the treatment and remission of ALL in children [8].…”