Incidence of sinusoidal obstruction syndrome/veno-occlusive disease and treatment with defibrotide in allogeneic transplant: A multicentre Australasian registry study.

Abstract

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic haemopoietic stem cell transplantation. Defibrotide is an effective and safe pharmacological option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centres from Australia and New Zealand, this study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020. Patients who underwent allogeneic HSCT between 2016 and 2020 were identified from the ABMTRR. Data was extracted for a total of 3346 patients, 2692 from adult centres and 654 from paediatric centres, with a median follow up of 21.5 months and 33.3 months respectively. Descriptive statistics were used to describe the patient population, including the incidence of SOS/VOD and defibrotide use. Comparisons were made between patients not experiencing SOS/VOD, and those with the diagnosis, divided into defibrotide and no-defibrotide cohorts. Associations with overall survival and day 100 survival with variables such as gender, age, disease at transplant, source of stem cells, conditioning agents, SOS/VOD diagnosis and use of defibrotide were determined. The reported incidence of SOS/VOD was 4.1% in adult centres and 11.5% in paediatric centres. Defibrotide was administered to 74.8% of adult patients with SOS/VOD and 97.3% of paediatric patients. Significant variability of use, dose and duration of defibrotide was seen across the adult centres. Day 100 survival rate and median overall survival (OS) for patients managed with defibrotide was 51.8% and 103 days respectively for adult patients, and 90.4% and not reached for paediatric patients. In adults, older age at transplant, an HLA matched donor who was a non-sibling relative, and a diagnosis of SOS/VOD treated with defibrotide, were all associated with reduced OS. In paediatrics, the patient and transplant characteristics that were associated with a reduced OS were a diagnosis of SOS/VOD and donor relation as 2 or more HLA mismatched relative. A collaborative approach across Australasia to diagnose and manage SOS/VOD, in particular with respect to consistent defibrotide use, is recommended.