Higher angiopoietin-2 and VEGF levels predict shorter EFS and increased non-relapse mortality after pediatric hematopoietic SCT.

The roles of angiogenesis and angiogenic factors after allogenic hematopoietic SCT (HSCT) and during acute GVHD (aGVHD) are not known. Studies on pediatric patients are extremely scarce. Levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) were analyzed from blood samples of 67 consecutive patients. The levels were correlated with aGVHD grades, routine laboratory parameters and outcome. Pre-transplant Ang2 values correlated with the occurrence of intestinal aGVHD (P=0.009), whereas post-transplant measurements correlated with the severity of skin and liver aGVHD (P=0.03, P=0.04, respectively). Pre-transplant levels of VEGF were associated with the occurrence of skin aGVHD (P=0.04), whereas post-transplant levels correlated to the severity of intestinal aGVHD (P=0.04). High Ang2 levels were associated with shorter EFS (P=0.039) and increased non-relapse mortality (NRM) (P=0.009). In conclusion, higher Ang2 levels predict higher NRM and, with coexisting high VEGF, also shorter EFS after pediatric HSCT. Our results suggest that both pre- and post-transplant levels of Ang2 and VEGF seem to correlate to the clinical state of the patient. However, the pathophysiology of this connection needs further studies.