Risk Factors Associated with Liver Injury and Impact of Liver Injury on Transplantation-Related Mortality in Pediatric Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

In adults, hepatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with significant morbidity and transplantation-related mortality (TRM). However, there is a paucity of parallel data on the incidence of, and risk factors for, liver injury (LI) and the impact of LI on TRM in pediatric allo-HSCT recipients. We compared total bilirubin, direct bilirubin, and alanine aminotransferase values before allo-HSCT and at 1 month, day +100, and 12 months after allo-HSCT in 248 patients who received either a myeloablative conditioning (MAC) regimen (n = 109) or a reduced-toxicity/reduced-intensity conditioning (RTC/RIC) regimen (n = 139). LI was defined as grade >= 2 hyperbilirubinemia according to the National Cancer Institute's Common Terminology Criteria for Adverse Events 3.0/4.0 (total bilirubin, >1.95 mg/dL, 1.5 times above the upper limit of normal for our laboratory). Univariate and multi-variate logistic regression models were used to identify risk factors for LI and TRM. The incidence of LI at 1 month after allo-HSCT was 14.1%. The median bilirubin level was 3.5 mg/dL (range, 1.97 to 32.2 mg/dL). Only LI as defined by total bilirubin level, but not by direct bilirubin or alanine aminotransferase level, was found to be a significant predictor for TRM. The 1-year TRM was 60.7% (95% confidence interval, 42.6% to 78.7%) in patients with LI at 1 month after allo-HSCT, compared with 14.6% (95% confidence interval, 9.9% to 19.4%) (P<.0001) in patients those who did not have liver injury. Multivariate analysis identified age (P = .03), total body irradiation (P = .007), bacterial bloodstream infection (BBSI) (P = .001), and invasive fungal infection (IFI) (P = .002) as significant risk factors for developing LI at 1 month. On multivariate analysis for risk factors for TRM, only LI at 1 month after allo-HSCT (P < .0001), primary graft failure (P = .001), BBSI (P = .003), and systemic viral infection (P = .04) were identified as significant risk factors for TRM. LI before allo-HSCT conditioning was not associated with higher TRM. Although the incidence of LI in pediatric allo-HSCT recipients is low, LI is associated with very high TRM. BBSI and IFI are the primary risk factors for LI. (C) 2013 American Society for Blood and Marrow Transplantation.