Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children.

Transplant associated thrombotic microangiopathy (TA-TMA) and sickle cell disease (SCD) share features of endothelial and complement activation. Thus, we hypothesized that SCD is a risk factor for TA-TMA and that pre-hematopoietic cellular transplantation (HCT) markers of endothelial dysfunction and complement activation would be higher in SCD patients. Children who underwent haploidentical or matched sibling donor (MSD) first HCT between January 2015- June 2020 were included in this IRB approved, single institution, retrospective study. Of 115 children, 52 had SCD and 63 underwent HCT for non-SCD indications. There were no significant differences in severe grade III-IV acute graft versus host disease (GVHD) in SCD vs. non-SCD HCT recipients. The non-SCD cohort had significantly more CMV positive recipients, radiation containing preparative regiments, and PBSC graft sources (p=0<0.05); all described risk factors for developing TA-TMA. Despite this, 7/52 (13%) of SCD patients developed TA-TMA compared to 1/63 (2%) non-SCD patients (p=0.015). Risk was highest in those who underwent haploidentical HCT (OR 33, 95% CI 1.4 - 793.2). Adjusting for HLA match, GVHD, post HCT viral infection, stem cell source and myeloablation, SCD remained a risk for developing TA-TMA (OR 12.22, 95% CI 1.15- 129.6). In available pre-HCT samples, there were no differences in complement biomarkers in those with SCD and those without, though SCD patients did have significantly higher markers of endothelial activation, sVCAM-1 and p-selectin levels. In conclusion, children with SCD merit careful screening for TA-TMA post HCT, particularly those receiving a haploidentical HCT.