Pb1875: non-hematopoietic cell transplant-related veno-occlusive disease/sinusoidal obstruction syndrome (vod/sos) in solid tumor and hematologic malignancies: a systematic review

Topic: 4. Acute myeloid leukemia - Clinical Background: VOD/SOS is a serious liver injury caused by toxic damage to sinusoidal endothelial cells. It has historically been associated with conditioning regimens preceding hematopoietic cell transplant (HCT), but little is known about its epidemiology and characteristics outside the HCT setting. Aims: 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. Two authors independently screened titles/abstracts and full-text articles and assessed the methodological quality of studies. Data for predefined outcomes were extracted by one author and validated by a second author. Results: We identified 3544 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) treated with oxaliplatin-based chemotherapy (median 41%) and in patients treated with vincristine plus actinomycin D for Wilms tumor (median 14%). Non-HCT VOD/SOS cases were also identified in hematologic malignancies, including acute lymphoblastic leukemia (ALL) and acute myeloid lymphoma (AML) (Table 1). The proportion of cases described as moderate or severe ranged from 50%–100%. Diagnostic criteria were heterogenous. Rubbia-Brandt histological criteria were used in CLM. In other disease settings, including ALL and AML, 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. Summary/Conclusion: 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. Given the seriousness of VOD/SOS, clinicians should be vigilant for VOD/SOS even in patients who have not undergone HCT. 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.Keywords: Veno-occlusive disease, Chemotherapy