Allogeneic hematopoietic stem cell transplantation for a pediatric case of myelodysplastic syndrome with germline DDX41 mutation

According to the 2016 World Health Organization classifcation, a germline DEAD-box helicase 41 gene (DDX41) mutation with myeloid neoplasms(MNs) has been newly classifed. Such mutations are clearly linked to late-onset MNs, with patients typically presenting in middle to old age and often manifesting as high-risk AML or MDS. These patients are sensitive to hypomethylating agents, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently recognized as the curative treatment modality. However, pediatric cases of MNs associated with germline DDX41 mutations are extremely rare, resulting in significant gaps in understanding their clinical characteristics, treatment strategies, and prognostic data. This article reports a pediatric patient with high-risk myelodysplastic syndrome (MDS-EB-2) associated with a germline DDX41 mutation (c.316_320del) who underwent unrelated cord blood allogeneic hematopoietic stem cell transplantation. An 8-year-old female patient achieved bone marrow remission with azacitidine and venetoclax and subsequently underwent allogeneic hematopoietic stem cell transplantation from an unrelated umbilical cord blood donor, The conditioning regimen included fludarabine, decitabine, busulfan, and cyclophosphamide, leading to sustained donor engraftment. Post-transplant complications included HHV-6 encephalitis and grade III acute graft-versus-host disease (aGVHD) of the skin and gut, which were managed and controlled. At the 13-month follow-up, the patient remained in complete hematologic remission without recurrence. This case suggests that allo-HSCT is a feasible curative option for children with high-risk MDS and germline DDX41 predisposition, highlighting the critical importance of screening potential donors for the same mutation.