Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: Prophylaxis and treatment controversies

Table 2 Randomized controlled trials of ursodeoxycholic acid for hepatic veno-occlusive disease

Trial reference	Essell et al[26] 1998	Ohashi et al[27] 2000	Ruutu et al[28] 2002	Park et al[29] 2002
Blinding	Double-blind	Non-blind	Non-blind	Non-blind
Type of transplants	Allogeneic	Allogeneic or autologous	Allogeneic	Allogeneic or autologous
Donor	Related	Variable	Variable	NA
Stem cell source	Bone marrow	NA	Variable	NA
Conditioning	Busulfan and cyclophosphamide or busulfan alone	Variable	Variable	Variable
No. of patients (treatment vs control)	35 vs 32	71 vs 65	124 vs 120	82 vs 83
Treatment regimen	Ursodeoxycholic acid 300 mg BD (< 90 kg) or 300/600 mg BD (> 90 kg), given before conditioning till Day+80	Ursodeoxycholic acid 600 mg daily, given from Day-21 till Day+80	Ursodeoxycholic acid 6 mg/kg per day BD, given 1 d before conditioning till Day+90	Ursodeoxycholic acid 300 mg BD, heparin 5 units/kg per hour, given 12-24 h before conditioning till Day+30
Control	Placebo	No drug	No drug	Heparin alone
Age of patients (yr, treatment vs control)	Mean 38 (22-56) vs 37 (21-56)	Mean 34.5 vs 35.7	Median 38 (5-59) vs 40 (1-58)	Median 39 vs 38
VOD criteria	Seattle	Seattle	Baltimore, Seattle	Modified Seattle
Frequency of VOD (treatment vs control)	14.3% vs 40.6%	2.8% vs 18.5%	Baltimore 2.4% vs 4.2%; Seattle 11.3% vs 11.7%	15.9% vs 19.3%
Mortality at Day+100 (treatment vs control)	22.9% vs 40.6%	NA	NA	11.0% vs 10.8%

NA: Data not available; VOD: Veno-occlusive disease.