(1529) NT-proBNP as a Biomarker of Endotheliopathy in Pediatric Hematopoietic Cell Transplantation

Introduction: Hematopoietic stem cell transplantation (HSCT) can lead to endotheliopathy, such as thrombotic microangiopathy (TMA), sinusoidal-obstructive syndrome (SOS), and diffuse alveolar hemorrhage (DAH). Natriuretic peptides, NT-proBNP and BNP, have been studied as markers of endotheliopathy and elevation has been associated with critical care utilization in pediatric HSCT patients. Based on this, we hypothesized elevation in NT-proBNP would be associated with developing endotheliopathy within 100 days after HSCT in pediatric and young adult (YA) patients.

Methods: Our retrospective case-control study reviewed allogenic or autologous HSCT at St. Jude Children’s Research Hospital from 2016-2020. Cases were selected based on having an endotheliopathy event TMA, SOS, or DAH in the first 100 days after HSCT. Cases were matched with controls based on transplant protocol, age group, and transplant time-period. Baseline and near-event NT-proBNP levels in cases were compared to corresponding measures in the matched controls. The effect of the NT-proBNP levels on developing endotheliopathy was estimated using a conditional logistic regression.

Results: Sixty-two patients were included (31 cases, 31 controls). The near-event NT-proBNP was significantly higher in cases compared to controls (Mean: 3190, SD: 7152 vs. Mean: 729, SD: 1158, p-value=0.03, Wilcoxon Rank-sum), in contrast to baseline NT-proBNP (p-value=0.51). For every 1000 pg/mL increase in near event NT-proBNP, the odds of developing endotheliopathy within 100 days after HSCT increased by 35.9% (OR: 1.36, 95% CI: 0.97-1.91, p-value=0.08) adjusting for baseline NT-proBNP, baseline and near-event ejection fraction, and transplant number. Renal function and presence of pulmonary hypertension were similar between both groups and not included as covariates.

Conclusions: Pediatric and YA patients who received HSCT and had elevated NT-proBNP were more likely to develop endotheliopathy. Cardiac or renal factors did not explain this effect. The use of non-invasive accessible biomarkers, such as NT-proBNP, predictive of endotheliopathy could allow earlier diagnosis, intervention, and potentially prevent HSCT morbidity such as critical illness. NT-proBNP should be further validated as a potential biomarker of endotheliopathy in pediatric patients receiving HSCT.