Incidence of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease and Treatment with Defibrotide in Allogeneic Transplantation: A Multicenter Australasian Registry Study

John Coutsouvelis; Carl M Kirkpatrick; Michael Dooley; Andrew Spencer; Glen Kennedy; Maggie Chau; Gillian Huang; Richard Doocey; Tandy-Sue Copeland; Louis Do; Peter Bardy; Ian Kerridge; Theresa Cole; Chris Fraser; Travis Perera; Stephen R Larsen; Kate Mason; Tracey A O'Brien; Peter J Shaw; Lochie Teague; Andrew Butler; Anne-Marie Watson; Shanti Ramachandran; Jodie Marsh; Zulekha Khan; Nada Hamad

doi:10.1016/j.jtct.2023.03.014

Incidence of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease and Treatment with Defibrotide in Allogeneic Transplantation: A Multicenter Australasian Registry Study

Transplant Cell Ther. 2023 Jun;29(6):383.e1-383.e10. doi: 10.1016/j.jtct.2023.03.014. Epub 2023 Mar 18.

Authors

John Coutsouvelis¹, Carl M Kirkpatrick², Michael Dooley³, Andrew Spencer⁴, Glen Kennedy⁵, Maggie Chau⁶, Gillian Huang⁷, Richard Doocey⁸, Tandy-Sue Copeland⁹, Louis Do¹⁰, Peter Bardy¹¹, Ian Kerridge¹², Theresa Cole¹³, Chris Fraser¹⁴, Travis Perera¹⁵, Stephen R Larsen¹⁶, Kate Mason¹⁷, Tracey A O'Brien¹⁸, Peter J Shaw¹⁹, Lochie Teague²⁰, Andrew Butler²¹, Anne-Marie Watson²², Shanti Ramachandran²³, Jodie Marsh²⁴, Zulekha Khan²⁵, Nada Hamad²⁶

Affiliations

¹ Pharmacy Department, Alfred Health, Melbourne, Victoria, Australia; Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. Electronic address: John.coutsouvelis@monash.edu.
² Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
³ Pharmacy Department, Alfred Health, Melbourne, Victoria, Australia; Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia; Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁴ Department of Malignant Haematology and Stem Cell Transplantation, Alfred Health-Monash University, Melbourne, Victoria, Australia.
⁵ Cancer Care Services, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia; University of Queensland Medical School, St Lucia, Queensland, Australia.
⁶ Pharmacy Department, Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁷ Blood Transplant and Cellular Therapies, Department of Clinical Haematology & BTCT, Westmead Hospital, Westmead, New South Wales, Australia.
⁸ Auckland City and Starship Hospitals Stem Cell Transplant Programme, Auckland, New Zealand.
⁹ Pharmacy Department, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
¹⁰ Haematology Department, St Vincent's Hospital & The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
¹¹ Department of Haematology and Bone Marrow Transplantation, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹² Haematology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Blood Research Centre, Kolling Institute, St Leonards, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.
¹³ Children's Cancer Centre, Royal Children's Hospital, Parkville, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
¹⁴ Blood and Marrow Transplant Program, Queensland Children's Hospital, South Brisbane, Queensland, Australia.
¹⁵ Wellington Blood and Cancer Centre, Wellington Hospital, Newtown, Wellington, New Zealand.
¹⁶ Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
¹⁷ Clinical Haematology, Austin Health, Heidelberg, Victoria, Australia.
¹⁸ Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia; School of Clinical Medicine, UNSW Medicine and Health, Randwick Clinical Campus, Discipline of Paediatrics, University of New South Wales, Sydney, Australia.
¹⁹ Blood Transplant and Cell Therapies Program, The Children's Hospital, Westmead, New South Wales, Australia; Clinical Professor, Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
²⁰ Starship Blood and Cancer Centre, Starship Hospital, Grafton, Auckland, New Zealand.
²¹ Haematology Department, Christchurch Hospital, Christchurch, New Zealand.
²² Haematology Department, Liverpool Hospital, Liverpool, New South Wales, Australia.
²³ Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation, Perth Children's Hospital, Nedlands, Western Australia, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
²⁴ Townsville University Hospital, Douglas, Queensland, Australia.
²⁵ Australasian Bone Marrow Transplant Recipient Registry, Level 6, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
²⁶ Haematology Department, St Vincent's Hospital & The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia; Australasian Bone Marrow Transplant Recipient Registry, Level 6, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia; University of New South Wales, Sydney, Australia; University of Notre Dame Australia, Sydney, Australia.

PMID: 36934993
DOI: 10.1016/j.jtct.2023.03.014

Abstract

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT). Defibrotide is an effective and safe pharmacologic option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centers in 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 hemopoietic stem cell transplantation between 2016 and 2020 were identified from the ABMTRR. Data were extracted for a total of 3346 patients, 2692 from adult centers and 654 from pediatric centers, 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 without SOS/VOD and those with SOS/VOD, divided into defibrotide and no defibrotide cohorts. Associations with overall survival (OS) and day 100 survival with such variables as sex, age, disease at transplantation, stem cell source, conditioning agents, SOS/VOD diagnosis, and use of defibrotide, were determined. The reported incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. Significant variability in the use, dosage, and duration of defibrotide was seen across the adult centers. The day 100 survival rate and median OS for patients managed with defibrotide was 51.8% and 103 days, respectively, for adult patients and 90.4% and not reached, respectively, for pediatric patients. In adults, older age at transplantation, an HLA-matched nonsibling relative donor, and a diagnosis of SOS/VOD treated with defibrotide were associated with reduced OS. In pediatric patients, the patient and transplantation characteristics associated with reduced OS were a diagnosis of SOS/VOD and a ≥2 HLA-mismatched related donor. A collaborative approach across Australasia to diagnosing and managing SOS/VOD, particularly with respect to consistent defibrotide use, is recommended.

Keywords: ABMTRR; Allogeneic Transplantation; Defibrotide; SOS/VOD; Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease.

Publication types

Multicenter Study

MeSH terms

Adult
Cardiovascular Abnormalities* / complications
Cardiovascular Abnormalities* / drug therapy
Child
Female
Hepatic Veno-Occlusive Disease* / drug therapy
Hepatic Veno-Occlusive Disease* / epidemiology
Hepatic Veno-Occlusive Disease* / etiology
Humans
Incidence
Male
Registries
Syndrome
Transplantation, Homologous / adverse effects