Survival After Hematopoietic Stem Cell Transplantation in Diamond-Blackfan Anemia Syndrome: The Role of Iron Overload-A Systematic Review

We assessed the effect of iron overload (IO) on mortality and complications following hematopoietic stem cell transplantation (HSCT) in patients with Diamond-Blackfan anemia syndrome (DBAS) in a systematic review of individual participant data and cohort data from observational studies. PubMed and EMBASE were searched up to 24 November 2025. Eligible studies included English or Dutch observational studies of pediatric or adult patients with confirmed DBAS undergoing HSCT, with documented transfusion history and sufficient follow-up. Abstract-only and congress publications were excluded. The search identified 993 records, of which 42 studies comprising 443 patients were included. Mortality related to IO was inconsistently reported. When reported, infections (31 cases) and graft-versus-host disease (18 cases) were the most frequent causes of death. IO assessment varied substantially, with heterogeneous diagnostic criteria and measurement methods. Although it has been demonstrated that IO affects patient outcomes in DBAS, the available evidence is currently insufficient to determine its direct association with mortality after HSCT specifically. Risk of bias assessment using ROBINS-E indicated high risk of bias, mainly due to exposure measurement and missing data, resulting in very low certainty of evidence. The effect of IO on HSCT outcomes in DBAS cannot be determined due to heterogeneous exposure definitions and methodological limitations. Importantly, the absence of a demonstrable association should not be interpreted as evidence that IO is safe in the transplant setting. Pretransplant IO should therefore be considered a clinically relevant potential risk factor for posttransplant morbidity and mortality, although current DBAS-specific evidence is insufficient to quantify its independent effect on HSCT outcomes. Future studies should incorporate standardized biochemical and imaging-based assessment of iron burden and systematically report iron chelation strategies to improve understanding of its impact on transplant outcomes, particularly in older patients.