Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a severe and potentially fatal complication following allogeneic hematopoietic cell transplantation (alloHCT), traditionally considered an early post-transplant event occurring within the first three weeks. However, emerging evidence suggests that a significant proportion of cases present later, challenging the conventional diagnostic window and contributing to underdiagnosis. This study focuses on late-onset VOD/SOS—defined as onset beyond 21 days post-transplant—and its role as a critical yet unrecognized cause of multi-organ failure (MOF) in adult acute leukemia patients.
Using data from the EBMT registry, we analyzed 202 alloHCT recipients who died of MOF between 2010 and 2018. Applying revised diagnostic criteria, including the late EBMT scoring system, we identified 41 patients (20.3%) with late-onset VOD/SOS, all of whom had no prior diagnosis. These patients developed symptoms more than three weeks after transplantation, with median onset at day 37 (range: 22–96). Notably, 68% of these late cases were not recognized during clinical follow-up, despite clear signs such as rising bilirubin, progressive ascites, hepatomegaly, and unexplained weight gain.
Among patients with late VOD/SOS, 59% had advanced disease status beyond first complete remission (CR1), and 24% had pre-existing hepatic comorbidities. The use of gemtuzumab before transplant was significantly associated with late VOD/SOS (p = 0.Caldesmon Antibody Epigenetic Reader Domain 003), as were haploidentical or cord blood grafts (p = 0.013). Moreover, nearly all patients receiving mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis were transplanted with non-matched donors, suggesting a strong confounding effect of both graft source and immunosuppressive regimen.
Despite the absence of hyperbilirubinemia in some cases—presenting as “anicteric” VOD/SOS—the majority exhibited elevated bilirubin (>3 mg/dL) at death. Ascites was observed in 51%, hepatomegaly in 36%, and weight gain exceeding 2% of body weight in 43%. These findings indicate that late VOD/SOS can mimic other post-transplant complications, such as GVHD or infection, leading to misdiagnosis.TZEP7 Epigenetic Reader Domain
Survival after diagnosis was extremely poor, with a median survival of only 61 days in the VOD/SOS group versus 128 days in non-VOD/SOS-related MOF.PMID:35185601 This stark difference underscores the aggressive progression of untreated VOD/SOS and the narrow therapeutic window available for intervention.
Our results demonstrate that late-onset VOD/SOS is not rare but rather systematically underreported due to outdated diagnostic thresholds and lack of awareness. The revised EBMT criteria, which extend the diagnostic window beyond 21 days and accommodate non-icteric presentations, are essential tools for improving detection. Early recognition enables timely treatment with defibrotide, which has been shown to improve Day+100 survival rates by up to 55% in treated patients.
In conclusion, late-onset VOD/SOS is a major hidden driver of mortality in alloHCT recipients. Its delayed presentation and overlap with other conditions make it difficult to identify without deliberate clinical suspicion. Integrating updated diagnostic guidelines into routine practice, particularly in high-risk populations, is crucial for reducing preventable deaths. Increased vigilance, especially beyond the first month post-transplant, could transform outcomes for thousands of patients undergoing life-saving transplantation.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com