Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation

Abstract

BACKGROUND. Currently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differences between practices across institutions. Herein, we aimed to define risk groups for SOS occurrence using three proteins: L-Ficolin, Hyaluronic Acid (HA), and Stimulation-2 (ST2). METHODS.Between 2017 to 2021, we prospectively accrued 80 pediatric patients across 4 US centers. Biomarkers were tested by ELISA blind to patient groupings and associated with SOS incidence at day 35 post-HCT, and overall survival (OS) at day 100 post-HCT. Cutpoints were identified using retrospective cohorts and applied to the prospective cohort. RESULTS.Combination of the three biomarkers measured at day 3 post-HCT in the prospective cohort provided 80% (95%CI, 55-100%) sensitivity and 73% (95%CI, 62-83%) specificity for risk of SOS occurrence. Patients with low L-Ficolin were 9 times (95%CI 3-32) more likely to develop SOS, while patients with high HA and ST2 were 6.

How to prevent sinusoidal obstruction syndrome/veno-occlusive disease?

“…Patients with low L-ficolin concentrations had a 9-fold higher risk of developing SOS/VOD, while patients with high hyaluronic acid and ST-2 concentrations had a 6.5-fold (95% CI: 1.9-22.0) and a 5.5-fold (95% CI: 2.3-13.1) higher risk of developing SOS/VOD, respectively. These three markers also had prognostic significance for poorer survival in the period up to day +100 after HSCT [45]. Another study demonstrated that increased levels of IL-6 and tumor necrosis factor-alpha (TNF-α) after HSCT were associated with an increased risk of SOS/VOD [46,47].…”

“…Other biomarkers identified by various research groups include increased concentrations of vWF, thrombomodulin, soluble intercellular adhesion molecule 1 (sICAM-1), as well as decreased concentrations of vascular cell adhesion molecule 1 (VCAM-1), angiotensin 2 and L-ficolin [42][43][44]. Han et al [45] recently published the results of a study in which on day +3 after HSCT, they measured the concentrations of three proteins: L-ficolin, hyaluronic acid, and stimulation 2 (ST-2) protein belonging to the interleukin (IL) 1 receptor family. The use of a panel of these three biomarkers showed 80% [95% confidence interval (CI): 55-100%] sensitivity and 73% (95% CI: 62-83%) specificity in predicting the occurrence of SOS/VOD.…”

Decision curve analysis based on summary data

“…We conducted DCA/gDCA to assess the utility of using a sinusoidal obstruction syndrome (SOS) biomarkers-derived Cox regression predictive model to individualize SOS preemption in patients undergoing allogeneic stem cell transplant (n = 80). 29 Unlike the other three models where power was formally calculated, this model was preliminary without formal sample size calculation. AUC was 0.71, but CI regarding risk group predictions indicated large uncertainties in the calibration.…”