melphalan and Cholangitis

Light-chain deposition disease (LCDD) is a multisystemic disorder associated with plasma cell dyscrasias and multiple myeloma. It is histologically characterized by the deposition of a homogeneous, in electron microscopy granular, slightly eosinophilic material showing positivity usually for kappa light chains. In contrast to AL-amyloidosis, the material is negative for Congo red. LCDD mainly involves the kidneys as the predominant organ manifestation resulting in a nephrotic syndrome. However, involvement of other tissues such as liver and heart have been described. Here we report a case of severe ischemic cholangitis in a patient with multiple myeloma receiving chemotherapy with melphalan, prednisone, and lenalidomide. Histopathological analysis revealed LCDD of the hepatic arteries as the underlying cause. This is to our knowledge the first case of LCDD of terminal liver arteries as a cause of intrahepatic ischemic cholangitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangitis; Hepatic Artery; Humans; Immunoglobulin Light Chains; Ischemia; Lenalidomide; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone; Thalidomide

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.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Busulfan; Chemical and Drug Induced Liver Injury; Cholangitis; Cord Blood Stem Cell Transplantation; Cyclosporine; Female; Hematologic Diseases; Hematologic Neoplasms; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Immunosuppressive Agents; Incidence; Infant, Newborn; Liver Diseases; Liver Function Tests; Male; Melphalan; Middle Aged; Postoperative Complications; Risk Factors; Tacrolimus; Tissue Donors; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

Topics: Acute Disease; Amyloidosis; Cardiomyopathies; Cholangitis; Cholestasis; Female; Humans; Liver Diseases; Melphalan; Middle Aged