Discussion
MOF, GVHD, bleeding
BLEEDING, MOF, PATHOGENESIS, GVHD, COMPLICATIONS
Early identification with objective proteomic risk biomarkers may improve monitoring and management of SOS, with the goal to decrease risk of MOF. Because we have previously identified and validated L-ficolin, HA, and ST2 as SOS risk biomarkers, we next conducted measurements of L-ficolin, HA, and ST2 on days 3 and 7 after HCT in a prospective cohort of 80 pediatric patients to evaluate NPV and PPV of these risk biomarkers for SOS occurrence, as recommended in the 2014 NIH Consensus Development Project on biomarkers (To our knowledge, this is the only prospective pediatric study conducted to assess SOS risk biomarkers. Identification of optimal cutpoints for the 3 biomarkers was performed solely in 1 retrospective cohort (These 3 biomarkers do not predict other early complications. Notably, ROC analyses for the 3 biomarkers showed higher AUCs on day 3 compared with day 7, particularly for ST2, which might be explained by the fact that ST2 is a confounding marker of GVHD risk when measured on or after day 7 (Pathogenesis of the 3 markers, although multifactorial, includes endothelial injury. Indeed, L-ficolin, a major plasma complement-activating pattern-recognition lectin, is synthesized in the liver, secreted into the bloodstream, and is involved in homeostatic clearance of mitochondria (We also interrogated the markers as predictors of OS within 100 days after HCT. L-ficolin, HA, and ST2 were also found to be prognostic markers of OS using cutpoints as risk biomarkers. Although the SOS incidence was low, the severity and development to MOF in SOS patients was high. Using the 3-biomarker score, recipients with a positive score were 5.5 times more likely to die by day 100 (95% CI 1.1–28.4, Six out of the 10 patients diagnosed with SOS received defibrotide, while the other patients were not able to receive the treatment due to contraindications, particularly bleeding. This highlights the importance of early diagnosis based on revised criteria and early intervention (This study has its limitations, however. In this contemporary prospective cohort of 80 pediatric patients with known pre-HCT risk factors for SOS, 10 patients developed SOS, resulting in a 12.5% incidence that is lower than the 20% reported in the placebo group from the defibrotide prophylaxis study, which might be explained by more the permissive inclusion criteria as compared with the defibrotide study (We conclude that in this prospective cohort study, 3 plasma biomarkers of endothelial damage measured noninvasively, 3 days after HCT, were associated with SOS occurrence and OS. Assessing these markers could stratify patients at high risk for SOS who may benefit from preemptive intervention with defibrotide.