Comparison of IV Busulfan and Fludarabine Vs Oral Busulfan Plus Cyclophosphamide As Myeloablative Conditioning Regimens for Acute Leukemias and Myelodisplastic Syndromes

The Busulfan Cyclophosphamide (Bu-Cy) combination has been broadly used as a myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for patients (pts) affected by myeloid malignancies. The Busulfan Fludarabine (Bu-Flu), a newly introduced mieloablative conditioning regimen association showed, in several reports, less regimen related toxicities. We compared in a retrospective study the effectiveness and toxicity of both regimens.

From 12/2002 to 12/2010, 59 pts. affected by AML, CML, MDS and ALL were included in the study. Forty two pts. received Bu-Cy (oral Bu 1 mg/kg, every 6 hours × 16doses days -8 to -5 followed by Cy 60 mg/kg per day, days -4 and -3) and 17 pts. received Bu-Flu (Bu IV 3.2 mg/kg, once daily for four days and Flu 40 mg/kg /daily for four days, days – 6 to -3). There were no statistical significant differences between both groups comparing age, diagnosis, disease status and CD34+ cells infused. Regarding the cell source there were more patients in the Bu-Flu group that received peripheral blood stem cells and cord blood and more pts in the Bu-Cy were infused with bone marrow. Another imbalance was the use of more unrelated donors in the Bu-Flu arm. GVHD prophylaxis was with cyclosporine A or tacrolimus and metotrexate. Protective isolation and antibiotic prophylaxis was used in both groups.

Considering hematopoietic recovery, there were no differences in days to reach 500 granulocytes and 20.000 platelets. Transfusion requirements were without statistical significant differences. The following observations were statistically significant (p<0.001) favoring Bu-Flu: Pts receiving Bu-Flu required less hospital stay days (27,8 vs 35,6) and less days on antibiotics (8,5 vs 16,5). Acute GVHD incidence grade II to IV was 23,5% in the Bu-Flu arm vs 50% in the Bu-Cy group. Early TRM was 5,9% with Bu-Flu vs 16,6% with Bu-Cy. Overall survival and relapse rate at 1 year of follow up was 70.58% vs 50% and 23.5 % vs 30.9% for Bu-Flu and Bu-Cy respectively.

In our experience Bu-Flu is associated with lower toxicity, neutropenia duration, and severe acute GVHD. The overall survival and relapse rate are also superior. More pts should be included in a prospective study to confirm these observations.

No relevant conflicts of interest to declare.