Improved Survival with Ursodeoxycholic Acid Prophylaxis in Allogeneic Stem Cell Transplantation: Long-Term Follow-up of a Randomized Study of the Nordic Bone Marrow Transplantation Group
Abstract Abstract 488FN2 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 at the dose of 12 mg/kg/day from the day preceding the conditioning until day 90 post-transplantation. The median age was 39, range 1–59 years. 231 patients had a malignant hematological disease. 140 patients had a low-risk disease (acute leukemia in CR1, CML in CP1, or non-malignant disorder), 102 high-risk disease (all other). Of the donors 132 were siblings, 2 other related and 108 unrelated. TBI-containing conditioning was given to 219 patients. 190 patients received a bone marrow graft and 52 a blood stem cell graft. As GvHD prophylaxis 235 patients were given cyclosporine and methotrexate with (n=112) or without (n=123) corticosteroid. There were no significant differences in patient characteristics between the study groups. The results were reported after 1-year follow-up (Blood 100: 1977–1983, 2002). In the group given UDCA prophylaxis the survival was significantly better, the incidence of acute GvHD was lower, there were fewer patients with high bilirubin and ALAT levels, the non-relapse mortality was lower, and there were fewer deaths in GvHD. We report here the long-term outcome. The median follow-up of living patients was 155 (range 37–184) months. Two patients were lost early (12–15 months) for follow-up. The survival difference seen at one year remained similar in the long-term follow-up. At 10 years, 48 % of the patients given UDCA and 38 % of the control patients survived (p=0.037). The survival difference was highly significant among the low-risk patients (63 % vs. 46 %, p=0.019) but there was no difference among the high risk patients (25 % vs. 29 %). In the total patient material, the cumulative incidence of non-relapse mortality was significantly lower among the patients given UDCA (28 % vs. 41 %, p=0.031). There was no significant difference in the cumulative incidence (58 % in the UDCA group vs. 68 % in the control group among patients at risk, p=0.47) or severity of chronic GvHD. In the long-term follow-up there were no significant differences in liver problems between the study groups. The cumulative incidence of relapse did not differ significantly between the arms. In the UDCA group 23 % and in the control group 20 % of the patients had a relapse; among low risk patients 14 % vs. 12 %, respectively. There were seven secondary cancers in both study arms. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.