A PRSZT Registry Analysis of Prognostic Factors Influencing Survival and Relapse Rates After Second Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia.

A second allogeneic (allo-)hematopoietic stem cell transplantation (HSCT2) is a potential curative option for pediatric patients with acute lymphoblastic leukemia (ALL) following relapse after first allogeneic transplantation (HSCT1), but its efficacy is limited by high relapse rates and transplant-related toxicity in highly pretreated patients. This retrospective multicenter study analyzed 75 pediatric patients enrolled in the PRSZT registry who underwent HSCT2 between 2011 and 2020. Indications for HSCT2 were relapse in 55 patients (73%) and graft failure in 16 patients (21%). In 4 patients (6%), the indication could not be clearly determined due to incomplete documentation. At 2 and 5 years, overall survival (OS) was 48% and 40%, while relapse-free survival (RFS) was 35.2% and 29.9%. Relapse was the leading cause of mortality, occurring in 36% of patients post-HSCT2, with a median time to relapse of 8.2 months. Univariate analysis identified a longer duration of remission after HSCT1 (>6 months) as a predictor of improved OS (p = 0.013) and chronic graft-versus-host disease (cGVHD) after HSCT2 as beneficial for OS (p = 0.034) and RFS (p = 0.024). In multivariate analysis, older age (>10 years) (HR: 2.778, p < 0.01) and precursor T-cell ALL (HR: 6.62, p = 0.001) were associated with inferior OS, as well as with inferior RFS (HR: 2.2, p = 0.03; HR: 3.89, p < 0.005), while male sex (HR: 0.354, p = 0.02) and ATG administration (HR: 0.35, p = 0.019) predicted improved OS. Despite high relapse rates, HSCT2 remains a potentially curative treatment in a subgroup of patients. These findings highlight the need for better patient selection and the integration of novel immunotherapeutic strategies to further improve outcomes.