title: Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study.
abstract: We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. Electronic address: tapani.ruutu@hus.fi.
authors.forename: Tapani
authors.initials: T
authors.lastname: Ruutu
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Finnish Red Cross Blood Transfusion Service, Helsinki, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Juvonen
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Departments of Clinical Immunology and Medicine, Karolinska Hospital, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.affiliation: Department of Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Remes
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Departments of Clinical Immunology and Medicine, Karolinska Hospital, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Nihtinen
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Departments of Clinical Immunology and Medicine, Karolinska Hospital, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Hägglund
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Departments of Clinical Immunology and Medicine, Karolinska Hospital, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000328:Adult; D001663:Bilirubin / Q000097:blood; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D019653:Myeloablative Agonists; D014580:Ursodeoxycholic Acid; D001663:Bilirubin
keywords: Allogeneic stem cell transplantation; Survival; Transplant-related mortality; Ursodeoxycholic acid; Ursodiol