Early vascular toxicity after pediatric allogeneic hematopoietic stem cell transplantation

Treatment-related mortality and morbidity remain a challenge in hematopoietic stem cell transplantation (HSCT). In this retrospective, single-center study, we analyzed endothelial damage as a potential, common denominator and mechanism for the adverse effects. We evaluated the prevalence of key vascular complications and graft-versus-host disease among 122 pediatric patients with an allogeneic HSCT between 2001 and 2013. The spectrum and frequency of acute adverse events emerging ≤100 days post transplant were graded according to the CTCAE 4.03 and analyzed. We identified a total of 19/122 (15.6%) patients with vascular complications, fulfilling the criteria of capillary leak syndrome, veno-occlusive disease/sinusoidal obstruction syndrome or thrombotic microangiopathy. The patients had a poorer overall survival (77% versus 26%, p < 0.001). Nearly one half (56/122, 45.9%) had at least one, severe (grade 3 or 4) adverse event. Patients with vascular complications had more often edema/effusions (p = 0.023), thrombocytopenia (p = 0.001), gastrointestinal bleeding (p < 0.001), acute kidney injury (p < 0.001), ascites (p < 0.001) or bilirubin increase (p = 0.027). These endotheliopathy-related adverse events appeared early post HSCT, varied in their clinical phenotype and predicted a poor outcome. An unrelated donor but not previous exposure to leukemia or irradiation-based conditioning was identified as a risk factor for vascular complications and endotheliopathy.