Validating Ultrasound Biomarkers for Hepatic Sinusoidal Obstruction Syndrome in Pediatric Hematopoietic Cell Transplant Patients

• Status: Withdrawn
• Trial end date: 2025-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Hepatic veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) is a potentially fatal complication of hematopoietic cell transplant (HCT). Historically VOD/SOS has been clinically diagnosed using the modified Seattle criteria or the Baltimore criteria. The modified Seattle Criteria define VOD/SOS diagnosis is made when two of the following three criteria are present in a patient within 21 days of transplantation: hyperbilirubinemia (total serum bilirubin > 2 mg/dL), hepatomegaly or right upper quadrant liver pain, and weight gain (> 2% of baseline) or ascites. Other conditions like graft versus host disease, sepsis syndrome (fever and hypotension), cardiac failure, or tumor infiltration) have to be excluded. This definition was from a well-designed retrospective cohort study on 255 adult and pediatric HCT patients in which the VOD/SOS incidence was 21%. McDonald et al followed up this work with a prospective cohort study of 355 patients noting an incidence of VOD/SOS of 54%. These seminal studies have had a major impact on the field by defining clinical diagnostic criteria. An alternative diagnostic criteria (Baltimore criteria) was proposed by Jones et al as a part of a well-designed retrospective review of 235 HCT patients finding a VOD/SOS incidence of 22%. Jones defined VOD/SOS as the presence of hyperbilirubinemia (total serum bilirubin > 2 mg/dL) along with at least 2 of 3 other findings: hepatomegaly, ascites, and weight gain (> 5% of baseline).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Mercy Hospital Kansas City
• Collaborators: Children's Hospital Colorado; National Institutes of Health (NIH); Nationwide Children's Hospital; St. Jude Children's Research Hospital

Criteria

Inclusion Criteria:

• HCT patient under 25 years of age with

• myeloablative conditioning,

• prior liver damage or

• other high risk factor:

• Neuroblastoma,

• HLH,

• Osteopetrosis,

• Thalassemia,

• Treatment with inotuzumab or gemtuzumab within 3 months prior to HCT admission,

• Hepatic iron overload,

• Steatohepatitis,

• Active inflammatory or infection hepatitis or

• Any other condition which puts the patient at a higher risk of developing VOD).

Exclusion Criteria:

• Any patient who has contraindication to any of the ultrasound procedures (e.g. unable to hold still).