“Pre‐emptive strike”—the case for early treatment of hepatic sinusoidal obstruction syndrome with defibrotide

Abstract

The initial signs of hepatic sinusoidal obstruction syndrome (HSOS) can be challenging to recognize in children, especially outside the hematopoietic stem cell transplantation setting. To assist clinicians to promptly identify HSOS, the European Society for Blood and Marrow Transplantation has proposed pediatric HSOS diagnostic criteria which emphasize unexplained consumptive and transfusion-refractory thrombocytopenia. To highlight the importance of these "bellwether" early signs of HSOS and the efficacy of pre-emptive treatment with defibrotide, we describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment.

Use of inotuzumab‐ozogamicin in a child with Down syndrome and refractory B‐cell precursor acute lymphoblastic leukemia

“…A conditioning regimen with two alkylating agents and pre‐HSCT bilirubin concentration above the normal level were found to be predictive factors of SOS . Our case received successful prophylaxis with defibrotide, as reported in other settings …”

“…13,14 Our case received successful prophylaxis with defibrotide, as reported in other settings. 15 Our patient did not show relevant toxicity during IO treatment and he reached CR with MRD negativity, allowing him to undergo…”

Treatment of Sinusoidal Obstruction Syndrome With Defibrotide in Pediatric Cancer Patients Following Nontransplant-associated Chemotherapy: A Case Report and Review of the Literature

“…In contrast, the current standard for nontransplantassociated SOS/VOD, is supportive care, including blood products, sodium restriction, and diuretics. 7 Defibrotide, or defibrotide sodium, is a polydisperse mixture of single-stranded polydeoxyribonucleotides sourced from porcine and bovine mucosal DNA. 2,8 Its downstream effects include: increased tissue plasminogen activator and thrombomodulin expression; decreased von Willebrand factor and plasminogen activator inhibitor-1 expression; and reduced endothelial cell activation.…”

“…2 In another study, early severe consumptive thrombocytopenia, refractory to platelet transfusion, was shown to be an early clinical risk factor for SOS/VOD, and defibrotide was initiated preemptively with success. 7 Early treatment with defibrotide following an episode of nontransplant-associated SOS/VOD is a worthy consideration as it is well-tolerated, efficacious, and halts the progression of SOS/ VOD to MOD affording patients better outcomes. Furthermore, for post-HSCT SOS/VOD, ursodeoxycholic acid remains the prophylactic therapy of choice, however, prophylactic defibrotide is recommended for high-risk pediatric patients.…”

“…2 This therapy aids in restoring the balance between thrombosis and fibrinolysis, in addition to providing endothelial cells with protection from sustained injury during conventional chemotherapy treatment. 2,7 Defibrotide efficacy and safety has been scrutinized in several pediatric studies. In a recent phase 3 trial, the use of defibrotide as a therapy for SOS/VOD yielded a 23% survival improvement at day 100 in post-HSCT patients with MOD.…”