Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
JCI Insight. 2023 May 22;8(10):e168221. doi: 10.1172/jci.insight.168221.
BACKGROUNDCurrently, 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 3 proteins: L-ficolin, hyaluronic acid (HA), and stimulation 2 (ST2). METHODSBetween 2017 and 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 on day 35 after HCT, and overall survival (OS) on day 100 after HCT. Cutpoints were identified using retrospective cohorts and applied to the prospective cohort.RESULTSCombination of the 3 biomarkers measured on day 3 after 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 6.5 (95% CI 1.9-22.0) and 5.5 (95% CI 2.3-13.1) times more likely to develop SOS. These 3 markers also predicted worse day 100 OS - L-ficolin: HR, 10.0 (95% CI 2.2-45.1), P = 0.0002; HA: HR, 4.1 (95% CI 1.0-16.4), P = 0.031; and ST2: HR, 3.9 (95% CI 0.9-16.4), P = 0.04.CONCLUSIONL-ficolin, HA, and ST2 levels measured as early as 3 days after HCT improved risk stratification for SOS occurrence and OS and may guide risk-adapted preemptive therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT03132337.FUNDINGNIH.
目前，尚无实验室检测方法可用于分层造血细胞移植（HCT）后发生窦状隙阻塞综合征（SOS）的风险，SOS 是一种早期的内皮并发症。SOS 的风险生物标志物尚未在考虑到机构间实践差异的前瞻性队列中得到验证。在此，我们旨在使用 3 种蛋白（ficolin 蛋白 L、透明质酸（HA）和 ST2）定义 SOS 发生的风险组。
2017 年至 2021 年，我们在 4 个美国中心前瞻性地纳入了 80 例儿科患者。通过 ELISA 盲法检测生物标志物，并将其与 HCT 后 35 天的 SOS 发生率以及 HCT 后 100 天的总生存率（OS）相关联。使用回顾性队列确定临界点，并将其应用于前瞻性队列。
在前瞻性队列中，HCT 后第 3 天检测到的 3 种生物标志物的组合对 SOS 发生的风险提供了 80%（95%CI，55%-100%）的敏感性和 73%（95%CI，62%-83%）的特异性。低 ficolin 蛋白 L 的患者发生 SOS 的可能性高 9 倍（95%CI，3-32），而高 HA 和 ST2 的患者发生 SOS 的可能性高 6.5 倍（95%CI，1.9-22.0）和 5.5 倍（95%CI，2.3-13.1）。这 3 种标志物还预测了第 100 天较差的 OS- ficolin 蛋白 L：HR，10.0（95%CI，2.2-45.1），P=0.0002；HA：HR，4.1（95%CI，1.0-16.4），P=0.031；和 ST2：HR，3.9（95%CI，0.9-16.4），P=0.04。
HCT 后最早 3 天测量的 ficolin 蛋白 L、HA 和 ST2 水平提高了 SOS 发生和 OS 的风险分层，并可能指导风险适应的预防性治疗。
ClinicalTrials.gov NCT03132337。
NIH。
