title: Does early treatment with high-dose methylprednisolone alter the course of hepatic regimen-related toxicity?
abstract: Hepatic regimen-related toxicity (RRT) is a serious complication of stem cell transplantation. Cytokine activation may be involved in the pathogenesis. Corticosteroids are potent inhibitors of cytokine production, and, therefore could play a role in the treatment of hepatic RRT. Between January 1994 and June 1998, 28 of 782 consecutive transplant patients (3.6%) developed hepatic RRT (20 veno-occlusive disease (VOD) and eight liver dysfunction of uncertain etiology (LDUE) as defined by Seattle criteria), and were treated with high-dose methylprednisolone (MP, 500 mg/m2 i.v. every 12 h for six doses), initiated upon increase in serum total bilirubin to > or =4 mg/dl. Other causes of liver dysfunction were excluded. Response to therapy with high-dose MP was defined as reduction in total bilirubin by 50% within 10 days of initiation of MP. Overall, 17 patients (61%) responded to treatment (12 patients with VOD, five patients with LDUE). The bilirubin in responding patients decreased from a mean of 8.6 mg/dl (range, 4-17.9) at the start of MP to 4.1 mg/dl (range, 0.5-17.9) 10 days later. There were no statistically significant differences between responders and non-responders in the day treatment with high-dose MP was initiated (P = 0.38), total serum bilirubin (P = 0.17) and percent weight gain at the time high-dose MP was started (P = 0.10) or the calculated probability of fatal outcome from VOD (18% for responders, 23% for non-responders; P = 0.30). A lower pre-transplant DLCOc was observed among non-responders (P = 0.04). At 100 days post-transplant, hepatic RRT resolved in all 13 survivors who responded to high-dose MP, and in one non-responding patient. No serious toxicities due to high-dose MP were observed. We conclude that resolution of hepatic RRT occurred in the majority of patients treated with high-dose MP in this study; however, randomized controlled trials are required to determine the efficacy of high-dose MP for treatment of hepatic RRT.
authors.affiliation: Washington University School of Medicine, Division of Bone Marrow Transplantation and Stem Cell Biology, St Louis, MO 63110-1093, USA.
authors.forename: H
authors.initials: H
authors.lastname: Khoury
authors.forename: D
authors.initials: D
authors.lastname: Adkins
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: K
authors.initials: K
authors.lastname: Trinkaus
authors.forename: R
authors.initials: R
authors.lastname: Vij
authors.forename: G
authors.initials: G
authors.lastname: Miller
authors.forename: L T
authors.initials: LT
authors.lastname: Goodnough
authors.forename: J
authors.initials: J
authors.lastname: DiPersio
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008107:Liver Diseases / Q000209:etiology* / Q000517:prevention & control; D017093:Liver Failure / Q000209:etiology / Q000517:prevention & control; D008111:Liver Function Tests; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D012189:Retrospective Studies; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents; D001663:Bilirubin; D008775:Methylprednisolone