Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy.
نویسندگان
چکیده
BACKGROUND AND OBJECTIVES Hepatic veno-occlusive disease (VOD) remains a serious complication after hematopoietic stem cell transplantation (HSCT). Based on a protective effect of antithrombin III (ATIII) on endothelial cells, we assessed the incidence of VOD after pre-emptive ATIII replacement and the outcome of VOD after combined high dose defibrotide (DF) and ATIII therapy. DESIGN AND METHODS This prospective case series comprised two phases. In the first phase 71 children did not receive any specific VOD prophylaxis or therapy (controls). In the second phase 91 children were given pre-emptive ATIII replacement in case of decreased ATIII activity (< or =70%). If VOD was diagnosed clinically (according to modified Seattle criteria), high dose defibrotide (60 mg/day) and ATIII replacement therapy were combined. The severity of VOD was determined according to the degree of multiple organ dysfunction. RESULTS The incidence of VOD was similar in both groups (13/71, 18% vs. 14/91, 15%). All 14 patients in the second group who developed VOD showed decreased ATIII activity not more than 1 day prior to the clinical diagnosis of VOD. The resulting short duration of pre-emptive ATIII therapy failed to prevent VOD (OR 0.96). None of the patients (n=72) maintaining normal ATIII levels developed VOD. All 14 patients with VOD who received combined therapy achieved complete remission and 93 % (13/14) survived until day +100, compared to six survivors (46%) in the first group. INTERPRETATION AND CONCLUSIONS Pre-emptive ATIII administration did not alter the incidence of VOD. Combination treatment with ATIII and defibrotide was safe and yielded excellent remission and survival rates.
منابع مشابه
Long-awaited news for hepatic veno-occlusive disease.
In this issue of Blood, Palomo et al provide new insight into the mechanism of action of defibrotide as an endothelial protective agent, while Richardson et al present the encouraging final results of the phase 3 clinical study of defibrotide for the treatment of severe hepatic veno-occlusive disease (VOD), showing a 23% improvement in day +100 survival after hematopoietic cell transplantation ...
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Safety and efficacy of defibrotide for the treatment of severe hepatic veno-occlusive disease.
Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). VOD may occur in up to 62% of patients undergoing SCT, with onset generally within the first month after SCT. In severe cases, 100-day mortality is in excess of ...
متن کاملDefibrotide for Prevention and Treatment of Veno-Occlusive Disease in Adults: Single-Center Experience
Background: Hepatic veno-occlusive disease (VOD) has been reported at a rate up to 50% following intensive conditioning regimens used in allogeneic hematopoietic stem cell transplantation (AHSCT). Studies on the prophylactic effect of defibrotide to prevent hepatic VOD in adults are rare. Purpose: The research presented here aimed to evaluate whether propylactic defibrotide use can reduce incid...
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Hepatic sinusoidal obstruction syndrome (HSOS), also known as veno-occlusive disease, is a well-recognized toxic complication after autologous and allogeneic hematopoietic stem cell transplant, during treatment of Wilms tumor and rhabdomyosarcoma associated with actinomycin-D, and during acute lymphoblastic leukemia therapy due to oral 6-thioguanine. However, its occurrence in the context of ch...
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عنوان ژورنال:
- Haematologica
دوره 91 6 شماره
صفحات -
تاریخ انتشار 2006