Ruutu Tapani, Eriksson Britta, Remes Kari, Juvonen Eeva, Volin Liisa, Remberger Mats, Parkkali Terttu, Hägglund Hans, Ringdén Olle
Department of Medicine, Division of Hematology, Helsinki University Central Hospital, POB 340, FIN-00029 HUS, Helsinki, Finland.
Blood. 2002 Sep 15;100(6):1977-83. doi: 10.1182/blood-2001-12-0159.
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 microM (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-versus-host 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 transplant-related complications in allogeneic transplantation.
在一项前瞻性随机开放标签多中心试验中,研究了熊去氧胆酸(UDCA)在预防异基因干细胞移植后肝脏并发症中的作用。共有242例患者被分配接受(n = 123)或不接受(n = 119)UDCA,剂量为12 mg/kg/d,口服,从预处理前一天开始,直至移植后90天。在UDCA治疗组中,血清胆红素水平超过50 microM的患者比例显著较低(123例中的18例 vs 119例中的31例,P =.04),同样,超过丙氨酸转氨酶水平100 U/L的患者比例也较低。肝静脉闭塞病的发生率没有差异。与对照组相比,UDCA治疗组急性移植物抗宿主病(GVHD)的总体发生率有降低的非显著趋势,III至IV级急性GVHD的发生率显著降低(123例中的5例 vs 119例中的17例,P =.01),II至IV期肝脏和肠道GVHD以及III至IV期皮肤GVHD的发生率也显著降低。慢性GVHD的发生率或复发率没有差异。在接受UDCA的患者中,1年生存率显著更高,为71% vs 55%(P =.02),非复发死亡率更低,为19% vs 34%(P =.01),优于对照组。对照组因GVHD死亡的人数显著更多。总之,给予UDCA可减少肝脏问题和严重急性GVHD,并提高生存率。这些结果表明UDCA在预防异基因移植中与移植相关的并发症方面具有作用。