The Profile of Endothelial Function in Children with ALL Is Associated with the Risk Stratification Determining the Outcome – a Pilot Study

Endothelial dysfunction (ED) is characterized by impaired balance between pro- and anti-aggregatory, pro- and anti-inflammatory factors as well as vasodilative and vasoconstrictive action of numerous metabolic and signaling pathways. ED is an important factor worsening the outcome in severe diseases. The aim of this study was to assess if the profile of endothelial function during the treatment of ALL might be associated with the risk stratification and with the outcome.

N=18 children at age of 4–18 years with ALL, treated with the ALLIC- BFM 2002 protocol were investigated. Plasma levels of the NO pathway metabolites (L-Arginine, ADMA – an endogenous competive eNOS inhibitor), markers of endothelial inflammatory and aggregatory function (VCAM-1, ICAM-1, E-selectin, P-selectin and PAI-1), lipid peroxidation (MDA – malonyldialdehyde) were analyzed at baseline, then during the 33^rd and 78^th day of treatment. Results were compared between three subgroups: standard risk, intermediate risk and high risk.

Subjects in the high risk groups were characterized by increased baseline lipid peroxidation, as assessed by the MDA levels in comparison to those in the standard risk group (8.56±2.14U/ml vs. 3.57±0.81U/ml, respectively, p<0.05). In the high risk group low E-selectin levels at baseline (32.1±6.1ng/ml vs. 101.3±11.8ng/ml in the standard risk group, respectively, p<0.05), as well as high NO production at the beginning of the M protocol, assessed by the L-Arg/ADMA ratio (88.6±11.6ng/ml vs. 41.7±6.4ng/ml, respectively, p<0.05) were observed. Moreover, increase in the PAI-1 level during the therapy was associated with smaller risk for poor outcome.

Conclusions: Increased lipid peroxidation, low E-selectin at baseline, as well as increased NO bioavailability, decreased PAI-1 levels at the beginning of the M protocol are common feature in children classified to the high risk group. Low NO bioavailability at baseline and high at the beginning of the M protocol as well as decreased anti-inflammatory and antiaggregatory function of endothelium at the beginning of the M protocol are associated with higher risk for poor prognosis.

No relevant conflicts of interest to declare.