Non-hematopoietic cell transplant-related veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in solid tumor and hematologic malignancies: A systematic review.

Abstract

e24094 Background: VOD/SOS is a serious liver injury caused by toxic damage to sinusoidal endothelial cells. It has been linked to conditioning regimens preceding hematopoietic cell transplant (HCT) but little is known about its epidemiology and characteristics outside the HCT setting. We conducted a systematic review to examine the incidence, burden of illness, and management of non-HCT VOD/SOS. Methods: We searched MEDLINE, Embase (2002–2022), and relevant congress proceedings (2019–2022) for studies reporting incidence, diagnosis, clinical and patient characteristics, humanistic and economic burden, and treatments in non-HCT VOD/SOS. All study designs were eligible except case series of < 5 patients. Pyrrolizidine alkaloid-induced VOD/SOS was excluded. Results: We identified 3,544 records and included 80 studies; 58% were retrospective cohort studies. Sample sizes ranged from 5 to 12,941; 38% of the studies included > 100 patients. The highest incidences of non-HCT VOD/SOS were in patients with colorectal liver metastases (CLM) (median 41%) and Wilms tumor (median 14%) (table). Diagnostic criteria were heterogenous. Rubbia-Brandt histological criteria were used in CLM. In other disease settings, diagnosis varied and was based on clinical criteria (eg, McDonald, Seattle, or Baltimore). Management of VOD/SOS included defibrotide, supportive therapy (eg, fluid restriction, blood products) and switching/pausing chemotherapy. No usable data were found on humanistic/economic burden. Conclusions: Non-HCT VOD/SOS occurs in diverse disease areas, including hematologic and solid tumor cancers. Lack of consensus regarding diagnosis of non-HCT VOD/SOS may indicate underdiagnosis. Clinicians should be vigilant for VOD/SOS even in non-HCT patients. Defibrotide is approved for post-HCT VOD/SOS but there is no approved therapy for non-HCT VOD/SOS; future trials should focus on diagnosis and treatment outside the HCT setting, which represents a significant unmet need. A limitation of the current work is the suboptimal reporting and low methodological quality in some primary studies.[Table: see text]