Ravaioli Federico, Colecchia Antonio, Peccatori Jacopo, Pagliara Daria, Grassi Anna, Barbato Francesco, Masetti Riccardo, Sarina Barbara, Sica Simona, Cesaro Simone, Nozzoli Chiara, Assanto Giovanni Manfredi, Prezioso Lucia, Santarone Stella, Saglio Francesco, Vanni Ester, Olivieri Attilio, Delia Mario, Benedetti Edoardo, Zallio Francesco, Pane Fabrizio, Skert Cristina, Menconi Mariacristina, Benedetti Fabio, De Felice Francesco, Colecchia Luigi, Belotti Tamara, Alemanni Luigina Vanessa, Ursi Margherita, Marasco Giovanni, Roberto Marcello, Vestito Amanda, Dajti Elton, Garcovich Matteo, Bramanti Stefania, Taurino Daniela, Quagliarella Francesco, Ciceri Fabio, Prete Arcangelo, Pession Andrea, Festi Davide, Bonifazi Francesca
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Bone Marrow Transplant. 2025 Apr 19. doi: 10.1038/s41409-025-02570-w.
Hepatic Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a severe complication following hematopoietic stem cell transplantation (HSCT), traditionally diagnosed based on clinical criteria. This study aimed to evaluate the diagnostic performance of liver stiffness measurement (LSM) as a non-invasive tool for non invasive diagnosis of VOD/SOS. A multicentre clinical trial was conducted in Italy from April 2018 to December 2021, screening 1089 patients across 25 centers. VOD/SOS diagnosis followed established clinical guidelines, and patients underwent comprehensive clinical, laboratory, and imaging evaluations up to +100 days post-HSCT or until VOD/SOS diagnosis. LSM was measured pre-HSCT and on specific post-transplant days (ClinicalTrials.gov: NCT03426358). The study enrolled 774 adults and 167 children. The +100-day incidence of VOD/SOS HSCT was 5.53 and 5.26 in the overall and allo-HSCT population, higher in children (14.3%) than in adults (3.68%). The 100-day overall survival (OS) probability was 89.5% (overall) and 89.0% (allo-HSCT) while one-yr OS 79% and 78%, respectively, with outcomes varying by VOD/SOS occurrence and severity. LSM significantly differed between VOD/SOS patients and non-affected individuals at all post-HSCT time points, correlating with disease severity. A diagnostic algorithm was proposed, achieving ≥95% sensitivity and specificity, with a 6 kPa rule-out and 25 kPa rule-in cut-off, enhanced by the "three-time pre-HSCT rule." Survivors showed declining LSM over time, while non-survivors did not. Fully recovered patients had lower LSM than non-improvers. LSM also distinguished VOD/SOS from other liver complications within +100 days post-HSCT in both adults and children. In conclusion, LSM is a reliable, non-invasive diagnostic tool for VOD/SOS. LSM contribute to differential diagnosis and to treatment response as well. This study underscores the potential of LSM, combined with multidisciplinary expertise, to guide VOD/SOS diagnosis and management in HSCT patients, improving potentially the clinical outcomes.
肝静脉闭塞病/窦性阻塞综合征（VOD/SOS）是造血干细胞移植（HSCT）后的一种严重并发症，传统上依据临床标准进行诊断。本研究旨在评估肝脏硬度测量（LSM）作为一种用于VOD/SOS无创诊断的非侵入性工具的诊断性能。2018年4月至2021年12月在意大利开展了一项多中心临床试验，在25个中心筛查了1089例患者。VOD/SOS诊断遵循既定的临床指南，患者在HSCT后100天内或直至VOD/SOS诊断前接受全面的临床、实验室和影像学评估。在HSCT前以及移植后的特定日期测量LSM（ClinicalTrials.gov：NCT03426358）。该研究纳入了774例成人和167例儿童。在总体和异基因HSCT人群中，VOD/SOS HSCT的100天发病率分别为5.53和5.26，儿童（14.3%）高于成人（3.68%）。100天总体生存（OS）概率在总体人群中为89.5%，在异基因HSCT人群中为89.0%，而1年OS分别为79%和78%，其结局因VOD/SOS的发生和严重程度而异。在HSCT后的所有时间点，VOD/SOS患者与未受影响个体的LSM存在显著差异，且与疾病严重程度相关。提出了一种诊断算法，并实现了≥95%的敏感性和特异性，排除标准为6kPa，纳入标准为25kPa，通过“HSCT前三次测量规则”得到增强。幸存者的LSM随时间下降，而非幸存者则不然。完全康复的患者的LSM低于未改善者。LSM在成人和儿童中也能在HSCT后100天内将VOD/SOS与其他肝脏并发症区分开来。总之，LSM是一种用于VOD/SOS的可靠的非侵入性诊断工具。LSM有助于鉴别诊断和治疗反应评估。本研究强调了LSM结合多学科专业知识在指导HSCT患者VOD/SOS诊断和管理方面的潜力，有可能改善临床结局。
