The role of ursodeoxycholic acid (UDCA) in the prevention of hepatic complications after allogeneic stem cell transplantation was studied in a prospective randomized open-label multicenter trial. A total of 242 patients were allocated to receive (n ؍ 123) or not to receive (n ؍ 119) UDCA in the dose of 12 mg/kg/d orally from the day preceding the conditioning until day 90 after transplantation. In the UDCA-treated group a significantly smaller proportion of patients developed a serum bilirubin level exceeding 50 M (18 of 123 versus 31 of 119, P ؍ .04), and similarly a smaller proportion of patients exceeded the alanine aminotransferase level of 100 U/L. There was no difference in the incidence of veno-occlusive disease of the liver. Compared to the control group, in the UDCA-treated group there was a nonsignificant trend toward a lower overall incidence of acute graft-versushost disease (GVHD) and a significantly lower incidence of grade III to IV acute GVHD (5 of 123 versus 17 of 119, P ؍ .01), stage II to IV liver and intestinal GVHD, and stage III to IV skin GVHD. There was no difference in the incidence of chronic GVHD or in the relapse rate. Among the patients given UDCA, the survival at 1 year was significantly better, 71% versus 55% (P ؍ .02), and the nonrelapse mortality rate was lower, 19% versus 34% (P ؍ .01), than in the control group. There were significantly more deaths in GVHD in the control group. In conclusion, UDCA administration reduced hepatic problems and severe acute GVHD and improved survival. These results suggest a role for UDCA in the prevention of transplantrelated complications in allogeneic transplantation.
Summary:Among 551 consecutive recipients of allogeneic bone marrow transplants, 451 survived more than 3 months and were evaluated for chronic graft-versus-host disease (GVHD). Most of the donors were HLA-identical siblings or parents (n = 334). Patients with HLA-mismatched donors (n = 30) and matched unrelated donors (MUD) (n = 87) were also included in the study. In the analysis of all patients, the 5-year cumulative incidence of chronic GVHD was 45%. We analysed 34 risk factors. High recipient age was the single most important risk factor (P Ͻ 0.001). Other significant risk factors in multivariate analysis were: acute GVHD grades I-IV (P Ͻ 0.001), immune female donor to male recipient (P = 0.006) and chronic myelogenous leukaemia (CML), compared with all other diagnoses (P = 0.014). The cumulative 5-year incidence of chronic GVHD, with no significant risk factors present, was 9%, 29% with one risk factor, 53% with two, 68% with three and 75% with all four risk factors present. In patients with HLAidentical sibling donors and GVHD prophylaxis consisting of a combination of methotrexate (MTX) and cyclosporin A (CsA) (n = 208), increasing recipient age (P Ͻ 0.001) and CML (P = 0.007), were found to be significant risk factors for chronic GVHD. Finally, a multivariate analysis in recipients of bone marrow from unrelated donors (n = 89) showed recipient age alone (P = 0.006) to be significantly associated with chronic GVHD.
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