A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation

Background and Objectives. Veno-occlusive disease (VOD) is one of the most frequent complications after stem cell transplantation. We conducted a prospective survey of 244 hematopoietic stem cell transplants in children to determine the incidence of VOD, its main risk factors, treatment and effect on the transplant. Design and Methods. Two hundred and forty-four hematopoietic stem cell transplants (HSCT) performed in 220 pediatric patients from 1993 to 2003 were evaluated. The series included 127 males and 93 females with a median age of 6.7 years at the time of transplantation. Results. VOD was diagnosed following 26 of the 244 transplants (cumulative incidence 11%), but a higher incidence was found in patients with at least one known risk factor for VOD (cumulative incidence 20%). In multivariate analysis, risk factors for VOD were age < 6.7 years; type of VOD prophylaxis, and busulphan-containing conditioning regimens. Routine treatment of VOD was based on supportive care and, starting from 1999, defibrotide was used. All patients were monitored with daily Doppler ultrasound-(US) for early diagnosis of inversion of portal blood flow. Twelve patients developed inversion of portal flow (9 had severe VOD; 3 had moderate VOD) and were promptly started on fibrinolytic and anticoagulant therapy with heparin and recombinant tissue plasminogen activator (rt-PA). Hepatic flow reverted to normal in all 12 patients; only 4 patients ultimately developed multiorgan failure and died. The transplant-related-mortality (TRM) rate in patients with or without inversion of portal flow was 33% vs 7%, (p=0.1). The TRM in patients with or without VOD was 19% vs 8% (p=0.001). Interpretations and Conclusions. This study showed that younger age, type of VOD prophylaxis, and busulphan-based conditioning regimens are independent risk factors for VOD. Inversion of portal flow was found in 9 of 10 patients with severe VOD. Doppler US monitoring may be helpful in early identification of the patients with VOD-induced inversion of portal flow who might benefit from therapy with heparin and rt-PA.