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[DewDiligence]

GENT GTCB
Hepatic veno-occlusive disease in pediatric
stem cell transplantation: impact of pre-emptive
antithrombin replacement and combined
antithrombin/defibrotide therapy

[The conclusion is that combo treatment with defibrotide and antithrombin was effective but preemptive antithrombin monotherapy was not. Defibrotide is being developed by GENT for the treatment of VOD.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_...

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Haematologica. 2006 Jun;91(6):795-800.

Haussmann U, Fischer J, Eber S, Scherer F, Seger R, Gungor T.

Division of Immunology/Hematology/BMT, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.

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 (<=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 [control] 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.
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