ABSTRACTS: Oral Presentation Abstracts
Introduction: Veno-occlusive disease (VOD) is an early and potentially severe complication of bone marrow transplantation (BMT). In order to better control it, we tried to determine its incidence and risk factors.
Methods: Between 1995 and 2000, 171 children received 206 BMT, 96 boys (66%) and 75 girls, at a median age of 1.7 year (1 m-16 y). Primary diagnosis was immune deficiency in 75 (45%), leukemia in 22 (13%), macrophage activation syndrome in 19 (11%), and others in 43. 45 children had abnormal liver function tests before BMT. The graft was HLA-identical in 107 (67 intrafamilial, 40 unrelated donor), haploidentical in 90. The conditioning regimen was busulfan in 160 BMT (mean dose 18 mg/kg), with cyclophosphamide in 83%.
Results: Forty episodes of VOD occurred (20% of BMT), 40% in children younger than 6 months of age. Main symptoms were hepatomegaly (93%), weight gain (83%), ascites (67%), jaundice (65%). A significant decrease in prothrombin time was observed in 47%, a significant increase in creatinine in 38%.
The evolution was benign in 39% (no treatment), moderate in 31% (diuretics or pain killers), severe in 31% (persisting after day 100 or death). The survival of the whole group was 60% at 2 and 4 years. It was significatively different without (80% at 6 months, 61% at 4 years) and with (59% at 6 months, 51% at 4 years) VOD.
By multivariate analysis, two main risk factors were identified: age less than 6 months, and a dose of busulphan more than 16 mg/kg. The use of cyclophosphamide was a significant risk factor only in the univariate analysis.
Conclusion: Young age was not previously described as a risk factor and may be dependent on the large proportion of immune deficiencies in our population. The responsability of busulphan is probably related to the different pharmakokinetics of the drug in the very young child, and a smaller area under the curve. Interactions with cyclophosphamide may also play a role. The abnormal liver tests were not a risk factor like in other series, but no child here had a clinically significant liver disease before BMT.
As the survical is decreased when VOD occurs, a therapeutic intervention is needed and possible, especially in the very young children: close monitoring of the blood level of busulfan, and separation (24h) from the administration of cyclophosphamide to avoid interaction. The addition of other drugs, such as ursodeoxycholic acid or N-acetylcysteine, deserves further studies.