Hematology, University Hospital of Geneva, Switzerland.
Hematology, Hospital La Paz Institute for Health Research, Madrid, Spain.
Dis Markers. 2023 Apr 17;2023:7589017. doi: 10.1155/2023/7589017. eCollection 2023.
Sinusoidal obstructive syndrome (SOS) is a potentially fatal complication secondary to hematopoietic stem cell transplant (HSCT) conditioning. Endothelial damage plasma biomarkers such as plasminogen activator inhibitor-1 (PAI-1), hyaluronic acid (HA), and vascular adhesion molecule-1 (VCAM1) represent potential diagnostic tools for SOS.
We prospectively collected serial citrated blood samples (baseline, day 0, day 7, and day 14) in all adult patients undergoing HSCT at La Paz Hospital, Madrid. Samples were later analyzed by ELISA (enzyme-linked immunosorbent assay) for HA, VCAM1, and PAI-1 concentrations.
During sixteen months, we prospectively recruited 47 patients. Seven patients (14%) were diagnosed with SOS according to the EBMT criteria for SOS/VOD diagnosis and received treatment with defibrotide. Our study showed a statistically significant elevation of HA on day 7 in SOS patients, preceding clinical SOS diagnosis, with a sensitivity of 100%. Furthermore, we observed a significant increase of HA and VCAM1 levels on day 14. Regarding risk factors, we observed a statistically significant association between SOS diagnosis and the fact that patients received 3 or more previous lines of treatment before HSCT.
The early significant increase in HA levels observed opens the door to a noninvasive peripheral blood test which could have the potential to improve diagnosis and facilitate prophylactic and therapeutic management of SOS before clinical/histological damage is established.
窦状隙阻塞综合征(SOS)是造血干细胞移植(HSCT)预处理后潜在致命的并发症。内皮损伤的血浆生物标志物,如纤溶酶原激活物抑制剂-1(PAI-1)、透明质酸(HA)和血管细胞黏附分子-1(VCAM1),代表 SOS 的潜在诊断工具。
我们前瞻性地收集了马德里拉帕尔马医院所有接受 HSCT 的成年患者的枸橼酸盐血样(基线、第 0 天、第 7 天和第 14 天)。随后通过 ELISA(酶联免疫吸附测定)分析样品中 HA、VCAM1 和 PAI-1 的浓度。
在 16 个月的时间里,我们前瞻性地招募了 47 名患者。根据 EBMT 制定的 SOS/VOD 诊断标准,7 名患者(14%)被诊断为 SOS,并接受了 defibrotide 治疗。我们的研究表明,SOS 患者在第 7 天 HA 水平显著升高,早于临床 SOS 诊断,其敏感性为 100%。此外,我们还观察到第 14 天 HA 和 VCAM1 水平显著升高。关于危险因素,我们观察到 SOS 诊断与患者在 HSCT 前接受 3 次或更多次先前治疗之间存在统计学显著关联。
早期观察到 HA 水平的显著升高,为非侵入性外周血检测打开了大门,这可能有助于在临床/组织学损伤确立之前改善 SOS 的诊断,并促进其预防和治疗管理。