Using Ultrasound Elastography to Predict Which Pediatric HSCT Patients Will Develop Severe Sinusoidal Obstruction Syndrome

Abstract

Introduction Hepatic sinusoidal obstruction syndrome (SOS) is a complication of hematopoietic stem cell transplantation (HSCT). Severe and very severe SOS is associated with multi-organ failure and has ∼60% mortality. SOS is classified into mild, moderate, severe and very severe based on new European Society for Blood and Marrow Transplantation (EBMT) criteria. Defibrotide treatment is recommended for severe and very severe patients. Objective Our primary objective was to determine if hepatic ultrasound shear wave elastography (SWE) can predict SOS severity in pediatric HSCT patients. Methods This is a multi-site prospective cohort study evaluating the use of SWE in pediatric HSCT patients (0-21 years) from 10/2015 to 3/2018 at 2 pediatric institutions. Site 1 subjects underwent 1 SWE within 10-days prior to start of conditioning regimen and at days +5 and +14 after HSCT. Site 2 enrolled subjects at the time of clinical suspicion for SOS and subjects received SWE examinations every other day up to 10 exams during their inpatient stay. We examined 11 time-varying variables including weight, hepatomegaly, ascites, SWE and various Doppler ultrasound variables as predictors of maximum EBMT criteria severity grade. We used the median to summarize the SWE values. Missing data on explanatory variables ( Results 55 subjects were enrolled. Most patients were male (n=33, 55%) with a median age of 8 (range 0-20) years. 21 (35%) patients developed SOS, 15 (25%) had severe or greater disease by EBMT criteria. Busulfan use is associated with an average increase of 0.6 in EBMT grade, and a 100 cm/s decrease in main portal vein velocity is associated with an average increase of 1.3 in EBMT grade. Hepatomegaly, ascites, and higher SWE stiffness also appear to be associated with greater SOS severity (p 1.95 m/s was 87.5% sensitive and 85% specific for severe or very severe SOS. Seven of eight patients with severe or very severe SOS had SWE >1.95 m/s two to thirteen days before the date of severe SOS grading. Conclusion In a group of 12 clinical and ultrasound variables, SWE velocity was an excellent predictor of the patient developing severe SOS. SWE was able to predict severe SOS 2 to 13 days before the EBMT criteria with 87.5% sensitivity and 85% specificity.