TRANSPL CELL THER

Background: Hepatic sinusoidal obstruction syndrome (SOS) is a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) driven by endothelial injury. Post-transplant cyclophosphamide (PTCy) is widely used for graft-versus-host disease prophylaxis, but data on SOS incidence, risk factors, and outcomes in this setting are limited.

Objective: The present study investigates the incidence and outcomes of SOS in adults undergoing allo-HCT with PTCy-based prophylaxis.

Methods: This retrospective single-center study included 374 consecutive adult patients who underwent allo-HCT with PTCy between January 2014 and January 2025. SOS was diagnosed and graded according to established criteria. Endothelial activation was assessed using the Endothelial Activation and Stress Index (EASIX) at predefined peri-transplant time points.

Results: SOS occurred in 12 patients (3.2%), with a 100-day cumulative incidence of 2.7%. Six cases (50%) were moderate and six (50%) severe. Patients with myelofibrosis were markedly overrepresented (41.7% vs. 4.1%; P<0.001) and had an increased risk of SOS (HR 14.38, P<0.001). Median hospitalization was longer in SOS patients (46 vs. 29 days; P=0.01), and 16.6% required ICU admission. Ten patients (83.3%) received defibrotide and one underwent TIPS placement. Clinical response was observed in 91.7%, but seven patients (58.3%) died during follow-up, primarily from non-relapse mortality (NRM) (median 60 days). Two-year overall survival and NRM were 33.3% and 31.2% in SOS patients versus 71.8% and 12.6% in non-SOS patients. SOS was independently associated with higher NRM (HR 8.4, P<0.001) and inferior OS (HR 3.3, P=0.001). During the first 100 days, median EASIX values were higher in SOS patients. Higher log2-EASIX at pre-transplant evaluation (EASIX-PRE) and day 0 independently predicted SOS (HR 4.6; P=0.003).

Conclusion: SOS remains an uncommon but clinically significant complication following allo-HCT with PTCy, substantially impacting survival. EASIX is a readily available biomarker that may enable early risk stratification and support individualized preventive strategies in this setting.