Risk factors associated with liver injury and impact of liver injury on transplantation-related mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation

Kavita Radhakrishnan, Jacquelyn Bishop, Zhezhen Jin, Komal Kothari, Monica Bhatia, Diane George, James Jr H Garvin, Mercedes Martinez, Nadia Ovchinsky, Steven Lobritto, Yasmin Elsayed, Prakash Satwani

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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.

Original languageEnglish (US)
Pages (from-to)912-917
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

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Hematopoietic Stem Cell Transplantation
Transplantation
Pediatrics
Mortality
Liver
Wounds and Injuries
Bilirubin
Bacterial Infections
Alanine Transaminase
Incidence
Transplantation Conditioning
Multivariate Analysis
Chronic Idiopathic Jaundice
Logistic Models
Confidence Intervals
National Cancer Institute (U.S.)
Whole-Body Irradiation
Virus Diseases
Terminology
Liver Transplantation

Keywords

  • Bone marrow transplantation
  • Children
  • Hepatic injury
  • Hyperbilirubinemia
  • Reduced intensity conditioning regimen

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Risk factors associated with liver injury and impact of liver injury on transplantation-related mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation. / Radhakrishnan, Kavita; Bishop, Jacquelyn; Jin, Zhezhen; Kothari, Komal; Bhatia, Monica; George, Diane; Garvin, James Jr H; Martinez, Mercedes; Ovchinsky, Nadia; Lobritto, Steven; Elsayed, Yasmin; Satwani, Prakash.

In: Biology of Blood and Marrow Transplantation, Vol. 19, No. 6, 06.2013, p. 912-917.

Research output: Contribution to journalArticle

Radhakrishnan, Kavita ; Bishop, Jacquelyn ; Jin, Zhezhen ; Kothari, Komal ; Bhatia, Monica ; George, Diane ; Garvin, James Jr H ; Martinez, Mercedes ; Ovchinsky, Nadia ; Lobritto, Steven ; Elsayed, Yasmin ; Satwani, Prakash. / 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: Biology of Blood and Marrow Transplantation. 2013 ; Vol. 19, No. 6. pp. 912-917.
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T1 - Risk factors associated with liver injury and impact of liver injury on transplantation-related mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation

AU - Radhakrishnan, Kavita

AU - Bishop, Jacquelyn

AU - Jin, Zhezhen

AU - Kothari, Komal

AU - Bhatia, Monica

AU - George, Diane

AU - Garvin, James Jr H

AU - Martinez, Mercedes

AU - Ovchinsky, Nadia

AU - Lobritto, Steven

AU - Elsayed, Yasmin

AU - Satwani, Prakash

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - Bone marrow transplantation

KW - Children

KW - Hepatic injury

KW - Hyperbilirubinemia

KW - Reduced intensity conditioning regimen

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