Evaluation of Reversed Administration Order of Busulfan (BU) and Cyclophosphamide (CY) as Conditioning on Liver Toxicity in Allogenic Hematopoietic Stem Cell Transplantation (ALLHSCT)

Abstract

Background: Busulfan (BU) in combination with cyclophosphamide (CY) is used as an effective conditioning regimen in hematopoietic SCT. Busulfan, depletes glutathione level in liver and causes elevated levels of CY metabolites. Cyclophosphamide metabolites are highly toxic for sinusoidal endothelial cells and cause VOD/ SOS with high mortality rate.

Materials and Methods: Between September 2013 and September 2015, all adult patients with acute leukemia who were candidates for myeloablative allogenic SCT and were admitted to Stem Cell Transplantation center were enrolled in this prospective randomized clinical trial. We tested the hypothesis that reverse administration from BU-CY (n=28) to CY-BU group (n=27) would reduce liver toxicity.

Results: Liver function tests were significantly higher in the BU-CY group between day -1 and +4 (p<0.05), but VOD/SOS was not diagnosed in both groups. The incidence and severity of acute GVHD was higher in the BU-CY group, but not statistically significant. Engraftment and mortality rate were not different.

Conclusion: These data support the concept that CY-BU is associated with less liver toxicity, suggesting CY-BU is superior to BU-CY as conditioning.