Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation.

Systematic review and meta-analysis of randomized trials in people undergoing hematopoietic stem cell transplantation, including both autologous and allogeneic transplants and both adults and children. The review compared prophylactic medications against placebo, no treatment, or alternative prophylactic regimens and assessed hepatic veno-occlusive disease incidence, survival, mortality, quality of life, and adverse events.

This systematic review evaluated prophylactic regimens used around hematopoietic stem cell transplantation, most notably ursodeoxycholic acid, heparin or low molecular weight heparin, defibrotide, glutamine, antithrombin III, prostaglandin E1, and fresh frozen plasma. Regimens varied widely across trials, including oral ursodeoxycholic acid started before conditioning or around day -21 through day 80, intravenous heparin or LMWH during conditioning through engraftment or day 28 to 30, and intravenous defibrotide 6.25 mg/kg every 6 hours from conditioning through day 30.

Overall, ursodeoxycholic acid showed the clearest benefit and may reduce hepatic veno-occlusive disease and mortality after hematopoietic stem cell transplantation, although the evidence was low or very low quality. Across four trials, ursodeoxycholic acid reduced hepatic veno-occlusive disease incidence, RR 0.60 (0.40 to 0.88), all-cause mortality, RR 0.70 (0.50 to 0.99), and mortality attributable to veno-occlusive disease, RR 0.27 (0.09 to 0.87); overall survival was not clearly improved, HR 0.83 (0.59 to 1.18). Defibrotide showed a possible reduction in veno-occlusive disease incidence, 12.2% vs 19.6%, RR 0.62 (0.38 to 1.02), but not mortality, and adverse events were higher, RR 18.79 (1.10 to 320.45). Evidence was insufficient to support heparin, low molecular weight heparin, glutamine, fresh frozen plasma, antithrombin III, or prostaglandin E1 for prophylaxis.

The evidence base was low to very low quality, with many small trials, wide confidence intervals, and heterogeneous prophylactic regimens, doses, and comparators. Several outcomes were inconsistently reported, and harms data were limited or imprecise. The optimal ursodeoxycholic acid regimen was not defined, and findings may not generalize well across transplant types, ages, or centers.