Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood

Abstract Background Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT). Methods We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included. Results Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post‐DF era (2020–2023, n = 58) than in the pre‐DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post‐DF era than in the pre‐DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS ( p < .01) in comparison to non‐early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR] = 10.4, p = .01) and juvenile myelomonocytic leukemia (OR = 8.98, p = .04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS. Conclusions Early DF therapy improves the severity and survival outcomes of post‐transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.