Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries following reduced-intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation, and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to the report by Hogan et al. (

Blood. 2004;103:78–84
). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease related to GVHD or sepsis (CLD) (n=15), GVHD (n=7), cholangitis lenta (n=5) and others (n=9). Median onsets of CLD, GVHD and cholangitis lenta were day 37, 40 and 22, respectively. Frequencies of grade 3–4 ALT elevation were comparable among the three types of hepatic injuries. Serum GTP was not elevated in any patients with cholangitis lenta, while 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3–4 GTP elevation. Multivariate analysis identified two risk factors for hyperbilirubinemia; grade II–IV acute GVHD (relative risk 2.23, 95% confidential interval (95% CI) 1.11–4.47, p=0.024) and blood stream infection (relative risk 3.77, 95% CI 1.91–7.44, p=0.00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems following RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Topics:
hematological diseases, liver injuries, umbilical cord blood transplantation, graft-versus-host disease, cholangitis, bloodstream infections, hyperbilirubinemia, toxic effect, allogeneic hematopoietic stem cell transplant, cholestasis

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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