Feasibility of 8 Gy TBI-Busulfan-Fludarabine Conditioning with Post-Transplant Cyclophosphamide for Pediatric High-Risk or Relapsed Acute Lymphoblastic Leukemia.
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BACKGROUND: Total body irradiation (TBI)-based myeloablative conditioning is standard for pediatric acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic cell transplantation (HCT), but conventional 12-13.2 Gy TBI carries significant long-term toxicities, and pediatric data on reduced-dose TBI combined with post-transplant cyclophosphamide (PTCy) remain limited. OBJECTIVES: To evaluate the feasibility of a reduced-dose 8 Gy TBI-busulfan-fludarabine (TBI-Bu-Flu) regimen with PTCy-based graft-versus-host disease (GVHD) prophylaxis in pediatric high-risk or relapsed ALL undergoing alternative donor HCT. STUDY DESIGN: We retrospectively analyzed 37 consecutive pediatric patients (≤18 years at diagnosis) who underwent alternative donor HCT (unrelated, n=8; haploidentical, n=29) between 2019 and 2024. All received G-CSF-mobilized peripheral blood stem cell grafts. RESULTS: Pre-transplant measurable residual disease (MRD) was negative in 25 of 32 evaluable patients (78.1%). All patients engrafted with complete donor chimerism by day +30. The cumulative incidence of grade II-IV acute GVHD, grade III-IV acute GVHD, and severe chronic GVHD was 51.4%, 10.8%, and 8.8%, respectively. With a median follow-up of 32.7 months, 3-year leukemia-free survival (LFS) and overall survival (OS) were 79.6% and 88.3%, respectively, with a relapse incidence of 20.4% and no observed non-relapse mortality (NRM). For 26 patients transplanted in CR2, 3-year LFS and OS were 77.7% and 91.3%, respectively. Pre-transplant MRD negativity was the only significant prognostic factor for both LFS and OS (P<0.001). CONCLUSIONS: 8 Gy TBI-Bu-Flu with PTCy is a feasible reduced-radiation conditioning platform, providing reliable engraftment and encouraging leukemia control with no NRM in pediatric high-risk or relapsed ALL. However, the GVHD incidence was higher than anticipated, indicating that the prophylaxis backbone should be optimized in future prospective studies with systematic late-effect monitoring.