Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases.
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.
Kusumi
Eiji
E
Department of Hematology, Toranomon Hospital, Tokyo, Japan. kusumi-tora@umin.ac.jp
Kami
Masahiro
M
Kanda
Yoshinobu
Y
Murashige
Naoko
N
Seki
Kunihiko
K
Fujiwara
Masayo
M
Koyama
Rikako
R
Komatsu
Tsunehiko
T
Hori
Akiko
A
Tanaka
Yuji
Y
Yuji
Koichiro
K
Matsumura
Tomoko
T
Masuoka
Kazuhiro
K
Wake
Atsushi
A
Miyakoshi
Shigesaburo
S
Taniguchi
Shuichi
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001424:Bacterial Infections / Q000453:epidemiology; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology; D002761:Cholangitis / Q000453:epidemiology / Q000209:etiology; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000150:complications / Q000601:surgery*; D019337:Hematologic Neoplasms / Q000150:complications / Q000601:surgery; D006504:Hepatic Veno-Occlusive Disease / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D006932:Hyperbilirubinemia / Q000453:epidemiology / Q000209:etiology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007231:Infant, Newborn; D008107:Liver Diseases / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan; D016559:Tacrolimus