Allogeneic HSCT outcomes and impact of defibrotide prophylaxis on SOS after inotuzumab in pediatric B-ALL

Abstract Inotuzumab ozogamicin (InO) is a humanized, anti-CD22 antibody–drug conjugate with demonstrated use in the treatment of children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Sinusoidal obstruction syndrome (SOS), a life-threatening complication of hematopoietic stem cell transplant (HSCT), arises from injury to the sinusoidal endothelium and occurs at higher frequency and severity after treatment with InO. Defibrotide is widely used in the treatment of transplant-associated SOS; however, its role in prophylaxis is less clear. In this single-center retrospective analysis, we evaluated all children, adolescents, and young adults with relapsed or refractory B-ALL who underwent HSCT at our institution from 2016 to 2024 and compared outcomes between those who received InO during reinduction before HSCT with those who did not. In addition, we evaluated our institutional practice of employing defibrotide as SOS prophylaxis during HSCT for those with prior receipt of InO. Among children treated with InO, we found that 81% of this heavily pretreated population received InO as the last therapy before HSCT. We found no increase in nonrelapse mortality during HSCT in patients with previous receipt of InO. Among those who received defibrotide prophylaxis, we observed an incidence of transplant-related SOS similar to that observed among patients who did not receive InO during reinduction. Defibrotide prophylaxis was well tolerated, with low rates of adverse events and discontinuation. These results support the use of InO for children with relapsed or refractory B-ALL and suggest that defibrotide prophylaxis may reduce the incidence of SOS during HSCT after InO.