Fatal hepatic sinusoidal obstruction syndrome in a child with primary CNS lymphoma during induction therapy

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

“…The incidence of HSOS in children outside the HSCT setting has been reported to range between 1.2% to 8% for Wilms tumor, 12% for patients with ALL, and 1.2–5.3% for rhabdomyosarcoma; moreover, there are several case reports of children with medulloblastoma . There is a single case report of HSOS in recurrent yolk sac tumor, primary central nervous system lymphoma, idiopathic pulmonary hemosiderosis with autoimmune thrombocytopenia, and paraspinal PNET …”

“…Supportive care measures using blood products, sodium restriction, and diuretics remain the cornerstone in the management of HSOS . Treatment strategies using a number of different drugs, including heparin, antithrombin, recombinant human tissue plasminogen activator, N‐acetylcysteine, protein C concentrate, gabexate mesylate, and high‐dose methylprednisolone alone or in combination have demonstrated variable success and made no difference in outcome compared to defibrotide alone . Defibrotide modulates platelet activity, promotes fibrinolysis, decreases thrombin generation and activity, and reduces the circulating levels of plasminogen activator inhibitor type 1.…”

“…4,5,8,9 There is a single case report of HSOS in recurrent yolk sac tumor, primary central nervous system lymphoma, idiopathic pulmonary hemosiderosis with autoimmune thrombocytopenia, and paraspinal PNET. [14][15][16][17] The standardized Baltimore and modified Seattle criteria allow diagnosis of HSOS with good specificity (89% and 95%, respectively) but low sensitivity (56%). 5,12 This is exemplified by a report following a single-center retrospective study of 91 patients with Wilms tumor, who had undergone liver biopsy during nephrectomy after preoperative chemotherapy; 41 patients (45.1%) had histological evidence of HSOS but only 12 (13.2%) of them were clinically diagnosed with HSOS based on Seattle criteria.…”

“…7 Treatment strategies using a number of different drugs, including heparin, antithrombin, recombinant human tissue plasminogen activator, N-acetylcysteine, protein C concentrate, gabexate mesylate, and high-dose methylprednisolone alone or in combination have demonstrated variable success and made no difference in outcome compared to defibrotide alone. 5,7,9,15,20 Defibrotide modulates platelet activity, promotes fibrinolysis, decreases thrombin generation and activity, and reduces the circulating levels of plasminogen activator inhibitor type 1. Defibrotide lacks systemic anticoagulant activity, and severe hemorrhage or serious toxicities have not been reported in the literature.…”

Hepatic Sinusoidal Obstruction Syndrome During Chemotherapy for Childhood Medulloblastoma

“…There is a single report of HSOS occurring in a 2-year-old boy with recurrent yolk sac tumor receiving VAC chemotherapy20 and a report of HSOS after 2 doses of actinomycin-D in a 14-year-old girl with a paraspinal primitive neuroectodermal tumor who had received prior combination chemotherapy with etoposide, ifosfamide, cyclophosphamide, doxorubicin, vincristine, and external beam radiation partly involving the liver 20. In addition, HSOS is a well-reported complication of oral 6-thioguanine during acute lymphoblastic leukemia (ALL) therapy,21,22 while there have been anecdotal reports of HSOS during induction therapy for pediatric ALL23,24 and induction therapy for primary CNS lymphoma 25…”