Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation

A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997-2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1-21 days after HSCT (median 13 days). Age <= 2 years at transplant (odds ratio (OR) = 5.25, P = 0.011), BU-CY conditioning (OR = 5.16, P = 0.001), thalassemia major (OR = 3.97, P = 0.015), platelet engraftment beyond day +21 (OR = 8.67, P = 0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30-421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5-9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P = 0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR) = 23.6, P = 0.006), hepatic and cutaneous GVHD (HR = 8.15, P = 0.038), maximal weight gain >9% (HR = 6.81, P = 0.023), pleural effusion, intensive care unit admission, peak bilirubin >300 mu mol l(-1) (HR = 13.6, P = 0.016), day +21 bilirubin >200 mu mol l(-1) (HR = 33.9, P = 0.001), and rise of bilirubin >15 mu mol l(-1) per day within the first week (HR = 19.8, P = 0.006). Mortality was substantially higher if >3 predictors were present (HR = 33.9, P = 0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage.