Outcome of Second Conditioned Allogeneic Stem Cell Transplant in Children with Non-SCID Inborn Errors of Immunity

Graft failure post-allogeneic haematopoietic stem cell transplant (HSCT) is life threatening complication. The Inborn Errors Working Party (IEWP) conducted a retrospective study to examine outcome of second HSCT for children with non-SCID inborn errors of immunity (IEI). 159 children from 37 centres who received a second transplant between 2009-2020 were included in this analysis. The median interval between first and second HSCT was 6.9 months (0.7-155.2 months). The 5-year OS and EFS were 78% and 69%, respectively. Second HSCT for primary graft failure had a significantly lower OS (69%,55-83% versus secondary graft failure, 81%,73-89%; p=0.044) and EFS (52%,37-68% versus secondary graft failure, 75%,67-84%; p<0.001). Viral infections at second HSCT resulted in significantly lower EFS (p=0.030), but not OS (p=0.089). Improved EFS was observed in patients who received MAC/RTC (74%,66-81%) compared to NMA (50%,29-71%, p=0.003), but this association was not observed in OS. Upon multivariable analysis, cord blood was the only independent negative predictor for EFS (HR 4.9,1.3-18.7, p=0.020). The 1-year cumulative incidence (CIN) of all graft failure post-second HSCT was 13% (95% confidence intervals (CI),8-19%). The Day-100 CIN of grade II and grade III-IV aGvHD was 19% (13-25%) and 8% (4-13%), respectively. Whole blood chimerism >90% was reported in 84.3% at last follow-up. We report the first international experience with the largest cohort of second conditioned HSCT in non-SCID IEI to date. This study provides valuable insights into the clinical outcomes following second transplant, identifying key predictors of survival.