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Bone Marrow Transplant. 2018 May;53(5):591-599. doi: 10.1038/s41409-017-0066-4. Epub 2018 Jan 15.

Sinusoidal obstruction syndrome/veno-occlusive disease after high-dose intravenous busulfan/melphalan conditioning therapy in high-risk Ewing Sarcoma.

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Chemotherapy Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
Chemotherapy Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.
PhD, Istituto Ortopedico Rizzoli, Bologna, Italy.
Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
Unit of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.


This mono-institutional observational study was conducted to determine incidence, severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell transplantation (ASCT). During the past 10 years, 75 consecutive ES patients resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide therapy was started as soon as the medication was available. The variables analyzed as potential risk factors were: gender, patient's age at diagnosis, primary tumor site, disease stage, and prior radiation therapy (RT) given, focusing on RT liver exposure. The median age at diagnosis was 18.8 years. Five patients developed moderate to severe SOS/VOD (cumulative incidence, 6.67%). None of 32 pediatric patients (≤17 years) developed SOS/VOD (p = 0.0674). In univariate analysis, prior RT liver exposure resulted statistically significant (p = 0.0496). There was one death due to severe SOS/VOD. This study reports the largest series of high-risk ES patients treated with intravenous BU-MEL before ASCT. The incidence of SOS/VOD was lower when compared with other studies that used oral busulfan. Any prior RT liver exposure should be avoided. Earlier defibrotide treatment confirms to be effective.

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