Single-Center Experience of a Triple Drug Prophylaxis Regimen for Sinusoidal Obstructive Syndrome (SOS) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Abstract

Purpose Hepatic veno-occlusive disease (VOD) or SOS is a serious and potentially fatal complication of HSCT. Due to the limited amount of data regarding prophylactic agents for VOD, the goal of this study is to determine the efficacy of the triple prophylactic regimen utilized at North Shore University Hospital (NSUH), in preventing VOD until engraftment in patients undergoing allogeneic HSCT. Methods This retrospective cohort study included patients 18 years and older admitted to NSUH for an allogeneic HSCT during 2015-18. Patients that had known hypersensitivity to any of the prophylactic agents and/ or who were hemodynamically unstable within 24 hours of starting VOD prophylaxis were excluded. All patients received the standard regimen of continuous infusion heparin at a dose of 100 units/kg/day, Ursodiol 300 mg by mouth twice a day, and glutamine 15 gram in two divided doses. Patients were monitored closely for any weight changes and aggressive management with diuretics was utilized to avoid fluid overload and hepatic congestion. The primary outcome measure was to achieve VOD-free survival at engraftment and secondary outcomes was any adverse effects due to the regimen. Results The study included 109 patients, 61 male, 48 female, average age of 54 years (range 20-75 years) and average weight of 81.2 kg (range 42.8-155.5kg). The patients were in the hospital for an average of 31 days (range 20-93; median 28 days). None of the patients experienced fulminant SOS/VOD as per European Society for Blood and Marrow Transplantation (EBMT) criteria. Ultrasounds were done in 3 patients, with no abnormalities suggestive of VOD. Prior to engraftment 1 patient had ascites, 2 painful hepatomegaly, 1 right upper quadrant pain, and 23 (21.1%) concurrent organ dysfunction requiring supportive care such as oxygen supplementation (5.5%) and/or Intravenous fluids (6.4%). Patient's weight, bilirubin, AST, ALT, and serum creatinine were monitored at baseline and daily for any abnormalities. Patients experienced an average weight increase of 4% (0-7%), 11 patients (10%) had a bilirubin of greater then 2mg/dl but had no other criteria for SOS. Majority of the patients returned to their baseline (95%). Only 3 patients required discontinuation of heparin, no other adverse effects were reported. All patients received diuretics for an average of 7 days (range 1-42 days) and mean dose was 46mg/day (range 20- 160mg). Of note one patient died before engraftment with possible late onset VOD, patient had elevated bilirubin and weight gain of 18.6% with trace ascites. Patient had received Inotuzumab Ozogamicin as salvage treatment prior to HSCT. Conclusion No instances of classical SOS/VOD were reported in the 109 patients undergoing allogeneic HSCT receiving the triple therapy regimen. One patient had possible late onset VOD. The data suggests an efficacious role of the triple prophylactic drug combination in this setting.