Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide

Abstract

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.

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

“…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.…”

“…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. 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%).…”

“…Hepatic sinusoidal obstruction syndrome (HSOS), also termed veno‐occlusive disease of the liver, is a life‐threatening complication associated with hematopoietic stem cell transplantation (HSCT). However, HSOS is also well described outside the HSCT setting in children with Wilms tumor, rhabdomyosarcoma, medulloblastoma, and acute lymphoblastic leukemia (ALL) treated with conventional chemotherapy containing actinomycin‐D, cyclophosphamide, vincristine, 6‐thioguanine, and radiotherapy . HSOS in children is associated with significant morbidity, and mortality rates range from 7% to 100%.…”

“…However, HSOS is also well described outside the HSCT setting in children with Wilms tumor, rhabdomyosarcoma, medulloblastoma, and acute lymphoblastic leukemia (ALL) treated with conventional chemotherapy containing actinomycin-D, cyclophosphamide, vincristine, 6-thioguanine, and radiotherapy. [1][2][3][4][5][6][7][8][9] HSOS in children is associated with significant morbidity, and mortality rates range from 7% to 100%. The diagnosis of HSOS is based on two sets of guidelines known as the Baltimore and modified Seattle criteria, which have been used for the past three decades in pediatric and adult patients with HSCT (Table 1).…”

Defibrotide in the treatment of hepatic veno-occlusive disease

“…Due to toxicity, dose reduction was more often necessary at 110 mg/kg/day than at lower doses 62. A case of severe SOS has been reported in a child undergoing chemotherapy (vincristine, actinomycin D, and cyclophosphamide) for rhabdomyosarcoma: the child was successfully treated with DF without sequelae to the liver 63. A review of the current clinical findings concerning DF, primarily regarding its safety in the treatment and prophylaxis of SOS, together with relevant safety data regarding its use in other diseases, shows that DF is generally well tolerated.…”