Hepatic Sinusoidal Obstruction Syndrome During Chemotherapy for Childhood Medulloblastoma

Abstract

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 chemotherapy regimens for other childhood malignancies is rare. We report a 5-year-old girl with high-risk anaplastic medulloblastoma, who developed severe HSOS during her second cycle of maintenance chemotherapy, consisting of vincristine, cisplatin, and cyclophosphamide. She was treated with defibrotide with complete resolution of the HSOS. These findings and a review of the literature, highlight the occurrence of HSOS in children outside the established settings of hematopoietic stem cell transplantation, Wilms tumor, rhabdomyosarcoma, and acute lymphoblastic leukemia.

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

“…Few cases of SOS that were not in the HSCT setting, in patients with Wilms tumor, acute lymphoblastic leukemia and medulloblastoma have been reported [4,5]. Some conventional chemotherapeutic agents are associated with the development of SOS, including actinomycin-D and cyclophosphamide.…”

“…The doses of chemotoxic agents, their schedules, and the age of the patient are directly related to the risk of SOS. Actinomycin-D is used in the treatment of Wilms tumor and rhabdomyosarcoma, usually in combination with vincristine, anthracyclines, or alkylating agents [4]. Wilms tumor located at the right kidney, use of halothane as an anesthetic, and pre-existing liver diseases such as viral hepatitis have been suggested as risk factors for development of SOS [4,6].…”

“…Actinomycin-D is used in the treatment of Wilms tumor and rhabdomyosarcoma, usually in combination with vincristine, anthracyclines, or alkylating agents [4]. Wilms tumor located at the right kidney, use of halothane as an anesthetic, and pre-existing liver diseases such as viral hepatitis have been suggested as risk factors for development of SOS [4,6]. The use of 6-tioguanine is an important risk factor for SOS in acute lymphoblastic leukemia [7].…”

“…The use of 6-tioguanine is an important risk factor for SOS in acute lymphoblastic leukemia [7]. A fatal case of SOS was reported in a medulloblastoma patient after receiving a single course of chemotherapy comprised of vincristine, carboplatin, and lomustine [4]. …”

“…The following actions of defibrotide can help resolve the symptoms of SOS: (1) increasing the release of nitric oxide, prostacyclin, and prostaglandin E2; (2) decreasing the release of plasminogen activator inhibitor 1; and (3) decreasing the thrombin generation, tissue factor expression, and endothelin activity [12]. The therapeutic potential of defibrotide has largely been studied in patients who developed severe SOS after HSCT [4]. Regarding patients treated with conventional chemotherapy, successful treatment with defibrotide for SOS in childhood medulloblastoma, and adult patients with acute leukemia has been reported [4,13].…”