ESPE Abstracts (2019) 92 RFC3.5

Evaluation of Endothelial Function in Childhood Standard Risk Acute Lymphoblastic Leukemia Survivors: Role of Subclinical Markers and Identification of Preventable Factors

Patrizia Bruzzi1, Elena Bigi2, Francesca Felici3, Beatrice Righi3, Carmen Cano2, Monica Cellini2, Barbara Predieri1, Lorenzo Iughetti1


1Pediatric Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy. 2Oncology and Hematology Pediatric Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy. 3Post Graduate School of Pediatrics, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy


Background: Adult survivors from childhood malignancy are prone to accelerated atherogenesis and cardiovascular (CV) complications. In this population reliable tools are needed to detect preclinical onset of CV disease.

Aim: To assess subclinical markers of inflammation and endothelial dysfunction in young survivors from acute lymphoblastic leukemia (ALL) treated with chemotherapy without cranial irradiation (AIEOP 2000 and 2009 standard risk protocols).

Methods: Anthropometric parameters [height (H), body mass index (BMI), waist circumference (WC), hip circumference (HC), WC/H and WC/HC ratio], blood pressure, glucose and lipid profile, serum CV markers [Interleukin 6 (IL-6), Vascular Cell Adhesion Molecule (VCAM), Intercellular Adhesion Molecule (ICAM), Tumor Necrosis Factor-alfa (TNF-a), Endogenous secretory Receptor for Advanced Glycation Endproducts (Es-RAGE)]and ultrasound parameters of endothelial function (carotid intima–media thickness, c-IMT) were assessed in 28 ALL survivors (71% male, 18% prepubertal, aged 15.98±4.41 years) at least two years after the end of chemotherapy (mean follow-up 8.57±3.14 years) and in 22 sex- and age-matched controls (64% male, aged 16.59±5.60 years).

Results: ALL survivors exhibited low levels of Es-RAGE than controls (0.18±0.07 vs. 0.27±0.08 ng/ml, P<0.001). No other differences in serum CV markers were detected between survivors and controls. Among survivors, Es-RAGE values significantly correlated with BMI-SDS off-therapy (R2-0.42), WC/H ratio (R2-0.41), WC/HC ratio (R2-0.38) and with low-density-lipoprotein cholesterol (LDL-c; R2-0.43). IL-6 and TNF-a levels directly correlated with WC/H ratio (R20.41), WC/HC ratio (R20.51), triglycerides values (R20.40) and with diastolic blood pressure (DBP; R20.50), respectively. Moreover, in ALL survivors, mean c-IMT was within the normal range for age (0.55±0.14 mm, range 0.4-0.85) and correlated with systolic blood pressure (SBP; R20.56), DBP (R20.66) and LDL-c levels (R20.56). According to Weiss' definition, metabolic syndrome (MetS) was fully detected only in one ALL survivor. Nevertheless, 18% ALL survivors presented more than one MetS diagnostic criteria: 14% showed insulin-resistance, 25% dyslipidemia and 17.8% hypertension.

Conclusions: We demonstrated that in ALL survivors, as in general population, all the investigated CV markers correlate with modifiable clinical and biochemical parameters. Therefore, a healthy lifestyle should be encouraged soon after chemotherapy.The detection of low levels of Es-RAGE in ALL survivors could be due to their consumption in a chronic endothelial inflammatory condition that seems to be only partially reversible after chemotherapy.

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