Hepatic Veno-Occlusive Disease (VOD) after Hematopoietic Stem Cell Transplantation in Children: Retrospective Analysis in a Single Institution.

Introduction: Hepatic VOD, a potential life-threatening complication, occurs early after stem cell transplantation (SCT). Reliable predictive factors, effective prophylaxis and treatments need to be established in case of severe VOD. To better understand clinical findings in children, we evaluated clinical and laboratory characteristics of hepatic VOD undergoing SCT in children. Methods: We retrospectively reviewed the medical records of all patients (n=116) receiving SCTs in Pediatric BMT unit between May, 1991 to June, 2004. The definition of VOD required two of the following three clinical findings before D+21 following SCT: hyperbilirubinemia (>2 mg/dL), ascites or sudden weight gain, and painful organomegaly. Ursodeoxycholic acid was started before conditioning. No routine heparin prophylaxis was used. Lipo-prostaglandin E1 (0.5 ng/kg/min) was used in most of unrelated transplants (20/23). Results: VOD developed in 11 patients (12.8%). The median age was 9.8 years (range, 2 to 13.9 years). Underlying diagnoses were ALL (n=3), AML (n=2), acute biphenotypic leukemia, severe aplastic anemia, neuroblastoma, and myelodysplastic syndrome (n=1, each). The median day of onset of VOD was D+9 (range, D-3 to D+19). VOD was classified as moderate in 5 (45%) and severe in 6 (55%) cases. At the median of D+12 (range, D-5 to D+56), total serum bilirubin elevated over 2 mg/dL, with the peak bilirubin level at D+18 (range, D-5 to D+59). Maximum level of serum bilirubin was 2.9 mg/dL (range, 2.1 to 9.2) in moderate VOD and 7.3 mg/dL (range, 2.0 to 24.2 mg/dL) in severe cases. Various treatment modalities have been applied. Successful control of VOD was possible with tissue plasminogen activator and heparin (2/5, 40%), ursodeoxycholic acid (2/5, 40%), N-acetylcysteine (3/5, 60%), and defibrotide (1/2, 50%). All of 5 patients with moderate VOD survived (range, 6+ to 67+ months). Five of 6 (83%) patients with severe VOD died of VOD before D+100 (range, D+7 to D+64). Conclusion: This retrospective study showed that the incidence of VOD in children was 12.8%, and the mortality of severe VOD is still unacceptably high, necessitating further development of effective treatment.