Essell J H, Schroeder M T, Harman G S, Halvorson R, Lew V, Callander N, Snyder M, Lewis S K, Allerton J P, Thompson J M
Wilford Hall Medical Center, Lackland Air Force Base, Texas, USA.
Ann Intern Med. 1998 Jun 15;128(12 Pt 1):975-81. doi: 10.7326/0003-4819-128-12_part_1-199806150-00002.
Hepatic complications are a major cause of illness and death after bone marrow transplantation.
To confirm the results of a pilot study that indicated that ursodiol prophylaxis could reduce the incidence of veno-occlusive disease of the liver.
Randomized, double-blind, placebo-controlled study.
Tertiary care teaching hospital.
67 consecutive patients undergoing transplantation with allogeneic bone marrow (donated by a relative) in whom busulfan plus cyclophosphamide was used as the preparative regimen and cyclosporine plus methotrexate was used to prevent graft-versus-host disease.
Before the preparative regimen was started, patients were randomly assigned to receive ursodiol, 300 mg twice daily (or 300 mg in the morning and 600 mg in the evening if body weight was > 90 kg), or placebo.
Patients were prospectively evaluated for the clinical diagnosis of veno-occlusive disease, the occurrence of acute graft-versus-host disease, and survival.
The incidence of veno-occlusive disease was 40% (13 of 32 patients) in placebo recipients and 15% (5 of 34 patients) in ursodiol recipients (P = 0.03). Assignment to placebo was the only pretransplantation characteristic that predicted the development of veno-occlusive disease. The most significant predictor of 100-day mortality was the diagnosis of veno-occlusive disease. The difference in actuarial risk for hematologic relapse in patients with chronic myelogenous leukemia and nonhepatic toxicities between the two groups was not statistically significant (13% in the ursodiol group and 20% in the placebo group; P > 0.2).
Ursodiol prophylaxis seemed to decrease the incidence of hepatic complications after allogeneic bone marrow transplantation in patients who received a preparative regimen with busulfan plus cyclophosphamide.
肝脏并发症是骨髓移植后发病和死亡的主要原因。
证实一项初步研究的结果，该研究表明熊去氧胆酸预防可降低肝静脉闭塞性疾病的发生率。
随机、双盲、安慰剂对照研究。
三级医疗教学医院。
67例连续接受异基因骨髓移植（由亲属捐献）的患者，预处理方案采用白消安加环磷酰胺，并用环孢素加甲氨蝶呤预防移植物抗宿主病。
在预处理方案开始前，患者被随机分配接受熊去氧胆酸，每日两次，每次300mg（如果体重>90kg，则早晨300mg，晚上600mg），或安慰剂。
对患者进行前瞻性评估，以诊断肝静脉闭塞性疾病、急性移植物抗宿主病的发生情况及生存率。
安慰剂组肝静脉闭塞性疾病的发生率为40%（32例患者中的13例），熊去氧胆酸组为15%（34例患者中的5例）（P=0.03）。分配到安慰剂组是预测肝静脉闭塞性疾病发生的唯一移植前特征。100天死亡率的最显著预测因素是肝静脉闭塞性疾病的诊断。两组慢性粒细胞白血病患者血液学复发的精算风险差异及非肝脏毒性差异无统计学意义（熊去氧胆酸组为13%，安慰剂组为20%；P>0.2）。
对于接受白消安加环磷酰胺预处理方案的患者，熊去氧胆酸预防似乎可降低异基因骨髓移植后肝脏并发症的发生率。
