Endothelial syndrome as a life-threatening complication in haematopoietic stem cell transplantation

Background Endothelial syndromes (ES), including sinusoidal obstruction syndrome (SOS) and transplant-associated thrombotic microangiopathy (TA-TMA), contribute to hemopoietic stem cell transplantation (HSCT) failure. Some forms of acute graft-versus-host disease (aGVHD) have also been identified as severe ES complications. However, the impact of ES on HSCT outcomes has not been systematically studied. Methods We retrospectively analyzed the incidence and clinical impact of ES in 163 consecutive HSCT patients (median age: 58 years, IQR: 50-64) treated at a single center from February 2015 to May 2021. Patients still alive were censored at their last follow-up (November 30, 2022). The primary endpoint was cumulative incidence of non-relapse mortality (NRM), with relapse mortality (RM) and overall survival (OS) as secondary endpoints. Cox regression univariate models were used to test the association between ES and primary and secondary outcomes (NRM, relapse, and OS), comparing the effect of the covariates by the Wald test. A multivariate global model was then developed testing all independent covariates at univariate analysis for each endpoint (NRM, relapse, OS). Results Over a median follow-up of 23 months (IQR: 6-49 months), 81 patients (49.7%) died—36 (60.0%) with ES and 45 (43.7%) without. Relapse-related mortality occurred in 15% of ES patients and 22.3% of non-ES patients. NRM was significantly higher in ES patients (45.0% vs. 21.4%; Figure 1). Survival from NRM was worse in ES patients (51.8% vs. 76.7%; p=0.001), with 12- and 24-month survival estimates of 62.5% and 54.6% (vs. 84.0% and 78.1%). Cox regression (Table 1) confirmed ES as an independent predictor of NRM (OR 2.328; 95% CI 1.139-4.758; p=0.021), along with bone marrow as the stem cell source (OR 3.187) and aGVHD (OR 0.473). RM rates were comparable between groups (66.9% vs. 70.2%; p=0.732), but overall survival was lower in ES patients (34.7% vs. 53.9%; p=0.022), primarily due to increased NRM. However, ES was not independently predictive of OS in multivariable analysis. Conclusion ES significantly increases NRM and negatively impacts OS in HSCT patients, emphasizing the need for early recognition and targeted interventions. Future research should focus on identifying high-risk patients, optimizing prophylactic strategies, and developing targeted therapies to mitigate endothelial damage. Improved management of ES could enhance post-transplant survival and overall treatment success in HSCT recipients.Figure 1.Estimated survival rates (NRM) Table 1.Cox regression model for NRM