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 after 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, and 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 a 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 (CLD) related to GVHD or
sepsis (n = 15), GVHD (n = 7),
cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and
cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4
alanine aminotransferase elevation were comparable across the 3 types of hepatic
injuries. Serum gamma-glutamil
transpeptidase was not elevated in any patients with
cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil
transpeptidase elevation. Multivariate analysis identified 2 risk factors for
hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream
infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic
injuries are significant problems after RICBT, and that GVHD and blood stream
infection contribute to their pathogenesis.