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
Authors: Ruutu Tapani , Juvonen Eeva , Remberger Mats , Remes Kari , Volin Liisa , Mattsson Jonas , Nihtinen Anne , Hagglund Hans , Ringden Olle 
Published: October 2019

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.