Risk Factors, Mortality & Cost Analysis of Sinusoidal Obstructive Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Multi-Institutional Review

Background:

Sinusoidal obstructive syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplant (HSCT) characterized by hepatomegaly, jaundice, weight gain, and hyperbilirubinemia. SOS can be associated with prolonged hospitalizations and significantly increased health care costs in HSCT patients. However, studies evaluating the healthcare burden associated with SOS are limited. In this study we used a large inpatient Pediatric Health Information System database (PHIS) to complete a comprehensive review of pediatric patients undergoing HSCT to identify risk factors for SOS development and morbidity, mortality and healthcare resource utilization associated with this complication.

Methods:

PHIS is an administrative database containing data from 49 US children’s hospitals. We identified patients under 21 years admitted between 01/01/2016 - 12/30/2019 with a primary or secondary ICD-10 diagnosis of SOS and procedure code for HSCT. We collected the following: 1) Demographics: age, sex, race, geographic location; 2) Length of stay (LOS); 3) ICU admission; 4) Infections; 5) Graft-versus-host disease (GVHD); 6) Mortality; 7) Hospitalization costs; 8) Hospital resource utilization; and 9) Medications including defibrotide use. Differences in outcomes between patients with and without SOS were assessed by Chi-square tests or Wilcoxon nonparametric test for categorical and continuous variables respectively. Univariate and multivariate regression models were used to identify risk factors associated with SOS and the association of SOS on outcomes. P-values <0.05 were considered significant.

Results:

In 6,153 patients undergoing HSCT 263 patients (4.3%) experienced SOS. Median age at diagnosis was 5 years and males represented 60.8% of patients with SOS. The majority of patients experiencing SOS identified as white, though patients identifying as Asian or American Indian disproportionately experienced SOS. Allogeneic HSCT represented 81.75% of patients with SOS. Patient age, gender and race were not associated with significantly increased odds of SOS, the odds of SOS were 3 times greater in patients undergoing allogeneic transplantation (OR 3.0, 95% CI 2.2-4.1). Average LOS was significantly higher in patients diagnosed with SOS (71 days vs 43 days, p<0.001). ICU admission was more common in patients with SOS (68% vs 22%) with significantly longer ICU LOS as well (16.6 days vs 4.3 days, p<0.001). Mean hospitalization costs were greater in patients diagnosed with SOS ($803,956 vs $326,853, p < 0.001). Patients who experienced SOS had increased odds of developing GVHD (OR 2.7, 95%CI 1.9-3.8) and infection (OR 4.4, 95% CI 3.4-5.7). Mortality was greater in patients who developed SOS (17.5% vs 3.7%, p<0.001). However, SOS was not associated with a significant increase in mortality after adjusting for GVHD, infection and ICU admission (OR 1.4, 95% CI 0.9-2.1). In patients with medication data available (n=1956), defibrotide was administered to 67.1% of patients who experienced SOS and 5.8% of patients who did not. There was no significant difference in mortality between patients who received defibrotide and those who did not in patients with SOS (p=0.4).

Conclusions:

In this largest inpatient cohort of pediatric HSCT recipients to date, morbidity and healthcare resource utilization remain high among patients who experience SOS. This stresses the importance of early recognition and treatment of SOS, and the importance of novel therapeutic approaches to decrease the morbidity and improve quality of life in these patients.