Comparative study of Bu/Cy/ATG and Flu/Cy/ATG conditioning regimens for unrelated donor hematopoietic stem cell transplantation in severe aplastic anemia

Area of Science:

• Hematology
• Transplantation Immunology
• Oncology

Background:

• Unrelated donor hematopoietic stem cell transplantation (URD-HSCT) is a potential cure for severe aplastic anemia (SAA).
• The optimal conditioning regimen for URD-HSCT in SAA patients remains under investigation.
• Comparing Busulfan/Cyclophosphamide/Anti-thymocyte globulin (Bu/Cy/ATG) and Fludarabine/Cyclophosphamide/Anti-thymocyte globulin (Flu/Cy/ATG) protocols is crucial for treatment selection.

Purpose of the Study:

• To compare the efficacy and safety of Bu/Cy/ATG versus Flu/Cy/ATG conditioning regimens in SAA patients undergoing URD-HSCT.
• To identify the preferred conditioning regimen associated with improved survival and reduced complications.
• To evaluate the impact of conditioning regimens on overall survival (OS), failure-free survival (FFS), and specific infections like EBV viremia and post-transplant lymphoproliferative disorder (PTLD).

Main Methods:

• Retrospective analysis of clinical outcomes for 107 SAA patients who received URD-HSCT.
• Patients were divided into two groups based on conditioning regimen: Flu/Cy/ATG (n=63) or Bu/Cy/ATG (n=44).
• Statistical analysis included assessment of engraftment, graft failure, GVHD, CMV viremia, OS, FFS, EBV viremia, and PTLD, utilizing multivariate analysis for risk assessment.

Main Results:

• No significant differences were observed in engraftment, graft failure, GVHD, or CMV viremia between the two regimens.
• The Bu/Cy/ATG regimen demonstrated significantly higher 7-year OS (95.5%) and FFS (95.5%) compared to Flu/Cy/ATG (85.5% OS, 83.9% FFS).
• Multivariate analysis identified Bu/Cy/ATG as favorable for OS and FFS, and significantly reduced the risk of EBV viremia and PTLD. Subgroup analysis showed superior outcomes with Bu/Cy/ATG in patients over 30 years old.

Conclusions:

• The Bu/Cy/ATG conditioning regimen appears superior to Flu/Cy/ATG for SAA patients undergoing URD-HSCT, offering improved OS and FFS.
• Bu/Cy/ATG is associated with a reduced risk of EBV viremia and PTLD, suggesting a better safety profile.
• The Bu/Cy/ATG regimen may be the preferred choice for SAA patients, especially those older than 30, though further prospective studies are warranted.