Outcomes of Standard-dose vs. Low-dose Total Body Irradiation for Allogeneic Stem Cell Transplantation in Adults with Acute Lymphoblastic Leukemia

Abstract

Background: Conditioning regimens for allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) in adult Acute Lymphoblastic Leukemia (ALL) typically involve administering a ≥ 12 Gy dose of Total Body Irradiation (TBI), offering survival benefits but with potential acute and long-term complications. Within Myeloablative Conditioning (MAC) regimens, the optimal TBI dose in terms of outcomes and safety remains unknown, and the economic challenges of the standard approaches are pronounced in Low-middle Income Countries (LMIC). To address this gap, this study analyzes the outcomes of high-dose versus low-dose TBI in adult ALL patients undergoing allo-HSCT in Cali, Colombia.
Objectives: To compare the clinical outcomes of Myeloablative Conditioning (MAC) regimens based on a standard-dose TBI of ≥ 12 Gy (SD-TBI) versus regimens with low-dose TBI ≤ 4 Gy (LD-TBI) in adult patients with ALL and identical and haploidentical allo-HSCT.
Patients and methods: A retrospective cohort study was conducted with adult patients (≥18 years of age) with ALL between 2012 and 2021, who underwent allo-HSCT at a single center, in Cali-Colombia. The study population was divided into two MAC therapy groups: SD-TBI (≥ 12 Gy TBI) plus Flu and LD-TBI (≤ 4 Gy TBI) plus Bu and Flu. The primary outcome was Overall Survival (OS). Secondary outcomes included Disease-free Survival (DFS), Cumulative Incidence of Relapse (CIR), non-relapse mortality (NRM), Transplant-related Mortality (TRM), and acute and long-term transplant-associated complications. Outcomes were assessed at 12 months.
Results: A total of 100 patients were included, 39 received SD-TBI and 61 LD-TBI. Median age was 30 years, 97% of patients were classified as high risk, and only 49% were in first Complete Response (CR1). OS at 12 months was 59% and 47% in the SD-TBI and LD-TBI groups, respectively (p = 0.305). Relapse incidence at 12 months was 29% and 38.5% (p = 0.442). The incidence of grade II-IV acute graft versus host disease (aGVHD) was 24% in the SD-TBI vs. 46% in the LD-TBI group (p = 0.028). The relative risk (RR) for GVHD in the SD-TBI group was 0.52 (95% CI 0.27-0.98). The adjRR for donor type was 0.9 (95% CI 0.45-1.9) for haploidentical transplantation and RR 0.3 (95% CI 0.08 - 0.82) for HLA identical.
Conclusion: In ALL patients taken to allo-HSCT between 2012 and 2021, we found no significant differences in OS, DFS, TRM, or relapse incidence between SD-TBI and LD-TBI MAC regimens. The risk of aGVHD was lower in patients with SD-TBI, particularly those with HLA-identical donors. These results enhance Latin American representation in transplantation studies and have potential clinical implications. This study also serves as a base for future prospective studies and cost-effectiveness analyses needed for optimization of allo-HSCT conditioning regimens for ALL in LMIC.