# 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

## TL;DR

A modified conditioning regimen before stem cell transplants improves survival and reduces relapse in high-risk leukemia patients.

## Contribution

A novel modified conditioning regimen with reduced toxicity and improved outcomes for high-risk ALL patients undergoing transplantation.

## Key findings

- The modified regimen reduced the two-year relapse rate from 38.7% to 11.8% in high-risk ALL patients.
- The modified regimen improved 2-year overall survival to 71.6% compared to 50.6% in the traditional regimen.
- The modified regimen showed better disease-free survival (66.7% vs. 45.3%) with comparable transplant-related mortality.

## Abstract

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.

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.

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.

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.