Pretransplant immune dysregulation and survival after HSCT in pediatric inborn errors of immunity

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many inborn errors of immunity (IEIs), but the prognostic role of pretransplant immune dysregulation in pediatric patients remains unclear. We retrospectively studied 29 pediatric patients with genetically confirmed IEI undergoing HSCT between 2021 and 2025. Immune dysregulation was quantified using IDDA v2.1; HCT-CI and PARI were also calculated. 2-year overall survival (OS) was 79%, and event-free survival was 59%. Higher IDDA v2.1 scores were associated with inferior OS in univariate analysis (HR: 2.23 per five-point increase, P = 0.043) and remained associated in an exploratory multivariable model (HR: 2.76, P = 0.041). Harrell's C-statistic for OS was 0.722 for IDDA v2.1, 0.661 for HCT-CI, and 0.772 for PARI. Exploratory quadrant analyses suggested that IDDA v2.1 provides complementary information, identifying patients classified as lower risk by comorbidity indices who nonetheless had adverse outcomes. These findings support IDDA v2.1 as an adjunct pretransplant risk stratification tool in pediatric IEI.