title: Risk factors associated with liver injury and impact of liver injury on transplantation-related mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation.
abstract: 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 multivariate 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.
authors: Department of Pediatrics, New York-Presbyterian Morgan Stanley Children's Hospital, Columbia University, New York, New York 10032, USA.
authors: Kavita
authors: K
authors: Radhakrishnan
authors: Jacquelyn
authors: J
authors: Bishop
authors: Zhezhen
authors: Z
authors: Jin
authors: Komal
authors: K
authors: Kothari
authors: Monica
authors: M
authors: Bhatia
authors: Diane
authors: D
authors: George
authors: James H
authors: JH
authors: Garvin
authors: Mercedes
authors: M
authors: Martinez
authors: Nadia
authors: N
authors: Ovchinsky
authors: Steven
authors: S
authors: Lobritto
authors: Yasmin
authors: Y
authors: Elsayed
authors: Prakash
authors: P
authors: Satwani
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D016470:Bacteremia / Q000150:complications / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D016469:Fungemia / Q000150:complications / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000293:injuries* / Q000382:microbiology; D008111:Liver Function Tests; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists; D000410:Alanine Transaminase; D001663:Bilirubin