Durable Molecular Remission in TCF3::HLF-Positive Pediatric B-ALL Using Post-Transplant Azacitidine, DLI and Blinatumomab

Background: TCF3::HLF-positive B-cell acute lymphoblastic leukemia (B-ALL) is a rare, aggressive pediatric cancer characterized by chemotherapy resistance and high relapse rates following hematopoietic stem cell transplantation (HSCT), leading to historically poor outcomes. Novel therapeutic approaches are urgently required to enhance survival rates. Case Presentation: A 7-year-old girl with TCF3::HLF-positive B-ALL entered morphological remission post-induction/consolidation chemotherapy but had persistent minimal residual disease (MRD). After undergoing haploidentical HSCT, molecular relapse was identified through increasing TCF3::HLF transcripts despite MRD negativity. A post-transplant regimen was implemented, consisting of azacitidine (50 mg/m²/month), escalating donor lymphocyte infusions (DLI), and blinatumomab (15 µg/m²/day). This treatment achieved sustained molecular remission, with TCF3::HLF undetectable and MRD <.01% by April 2025, without significant toxicity. Conclusion: This case illustrates the potential of integrating epigenetic modulation (azacitidine), adoptive immunotherapy (DLI), and bispecific T-cell engagement (blinatumomab) to achieve sustained remission in TCF3::HLF-positive B-ALL. The synergy among these approaches may effectively address post-HSCT molecular relapse, presenting a management paradigm for this high-risk subtype. Further prospective studies are needed to validate this strategy.