A Novel Modified Bu/Vp16/cy/Flu/Ara-C Conditioning Regimen Enhances Outcomes for High-Risk Acute Lymphoblastic Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

PURPOSE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) effectively treats high-risk acute lymphoblastic leukemia (ALL), yet challenges persist due to post-transplant relapse and conditioning regimen toxicities. The determination of an appropriate preconditioning regimen is critical to improving patient outcomes. In our transplant center, we have modified the traditional busulfan (Bu)/cyclophosphamide (Cy)/etoposide (Vp16) protocol by adding fludarabine (Flu) and cytarabine (Ara-C), while reducing the dosage of Cy. This novel modification seeks to enhance transplantation outcomes for ALL patients.

METHODS: This study retrospectively collected clinical data from 88 high-risk ALL patients who received transplantation from June 2018 to December 2023. Among these patients, 40 received the novel modified Bu/Cy/Vp16/Flu/Ara-C conditioning protocol, while 48 received the traditional Bu/Cy/Vp16 regimen and served as a control group.

RESULTS: This study demonstrated a notably reduced incidence of cardiac toxicity in patients treated with the modified Bu/Cy/Vp16/Flu/Ara-C conditioning compared to those on the traditional Bu/Cy/Vp16 regimen. Furthermore, other types of conditioning-related toxicities were within acceptable limits in the modified regimen group. Regarding efficacy, the Bu/Cy/Vp16/Flu/Ara-C protocol significantly reduced the cumulative two-year relapse rate in high-risk ALL patients compared to the Bu/Cy/Vp16 scheme (38.7% (20.9%-52.5%) vs. 11.8% (0.2%-22.1%), p = 0.017). The modified regimen showed significant improvements in 2-year overall survival at 71.6% (57.1%-89.6%) compared to 50.6% (38%-67.3%) (p = 0.048), and in two-year disease-free survival at 66.7% (51.9%-85.6%) compared to 45.3% (33.1%-62.1%) (p = 0.015). Transplant-related mortality was comparable between the two groups. A subgroup analysis based on disease status (CR1 and ≥ CR2) revealed that high-risk ALL patients on the modified regimen had lower relapse rates and significantly better OS and DFS than those on the Bu/Cy/Vp16 scheme.

CONCLUSIONS: The novel modified Bu/Cy/Vp16/Flu/Ara-C conditioning significantly enhances the prognosis of high-risk ALL patients receiving transplantation, especially those in CR1.