Third Allogeneic Stem Cell Transplantation in Children: A Multicenter Analysis From the Spanish <scp>GETH</scp> ‐ <scp>TC</scp> Pediatric Group

Third allogeneic hematopoietic stem cell transplantation (HSCT3) is rarely performed in pediatric patients and is associated with high toxicity and mortality. Data on outcomes in this setting remain scarce. We conducted a retrospective multicenter study within the Spanish GETH-TC Pediatric group including 29 children and adolescents who underwent HSCT3 between 2011 and 2024 for malignant (n = 21) or nonmalignant (n = 8) diseases. Patient-, disease-, and transplant-related variables were analyzed, and survival outcomes were estimated using Kaplan-Meier methods. Engraftment was achieved in 22 patients (75.8%). Grade III-IV acute GvHD occurred in 7% and chronic GvHD in 11%. Severe viral infections were frequent (48%), as were bacterial (34%) and fungal infections (21%). By day +100, TRM was 31%, and overall mortality at last follow-up was 66%, predominantly transplant-related. Estimated 12-month overall survival (OS) and event-free survival (EFS) were 39.5% and 32.7%, respectively. Outcomes differed by indication: patients with malignant diseases had limited survival, particularly when transplanted with measurable residual disease, whereas outcomes were more favorable in nonmalignant disorders, with a 12-month EFS of 50%. Survival was also associated with preserved performance status. HSCT3 in children remains a high-risk procedure. Meaningful survival is restricted to carefully selected patients and appears more achievable in nonmalignant indications.