Optimizing Diagnostic Methods and Stem Cell Transplantation Outcomes in Pediatric Bone Marrow Failure: A 50-Year Single Center Experience

Abstract Purpose: Peripheral cytopenia, a frequent presenting symptom in pediatric patients, can be caused by bone marrow failure (BMF). In most cases, reversible causes such as iron deficiency or viral infections underly transient BMF. However, timely identification of patients with non-reversible BMF is of crucial importance to reduce the risks of invasive infections and bleeding complications. In these patients, BMF can be caused by a wide spectrum of underlying diseases including (pre)malignant disease, inherited bone marrow failure syndromes (IBMFS) and (idiopathic) aplastic anemia (AA). Most pediatric patients with severe persistent cytopenia, independent of the underlying cause, are offered allogeneic hematopoietic stem cell transplantation (HSCT) as curative therapy. Here we report on our management guidelines and HSCT outcomes of pediatric BMF patients. Methods: We formulated recommendations based on this 50 years’ experience, which were implemented at our center in 2017. By analysis of the HSCT cohort of 2017-2023, the 5-year outcome data is presented and compared to historical outcome data to pinpoint improvements and future challenges. In addition, outcomes of patients transplanted for an identified IBMFS is compared to AA outcomes to underline the often multiorgan disease in IBMFS with implications for long-term survival. Results: Overall and event-free survival of pediatric patients with irreversible BMF has improved tremendously independent of the underlying cause for BMF. This improvement is mainly related to better survival in the first months after HSCT. The long-term survival after HSCT is lower in IBMFS patients as compared to AA patients. Conclusions: Unbiased protocolized in-depth diagnostic strategies are crucial to increase the frequency of identifiable causes within the heterogeneous group of pediatric BMF. A comprehensive approach to identify the cause of BMF can prevent treatment delay and be useful to tailor treatment and follow-up protocols.