Efficacy Comparison of Oral Versus Intravenous Busulfan in a BuCy Conditioning Regimen for Allogeneic BMT.

Intravenous administration of busulfan (I-Bu) or targeted busulfan dosing has replaced oral administration of busulfan (O-Bu) in a conditioning therapy for BMT mainly due to erratic gastrointestinal absorption of oral busulfan. Several retrospective study results have demonstrated that use of I-Bu resulted in lower transplant-related morbidity and mortality compared to O-Bu, but the efficacy of I-Bu and O-Bu has not been compared. In this retrospective study, we compared the efficacy of I-Bu vs. O-Bu in a BuCy conditioning regimen for allogeneic BMT in a single institute. To avoid the bias of retrospective comparison, we restricted the patient eligibility to the followings:

1. patients with AML having intermediate or poor cytogenetic risk groups at the time of diagnosis,

2. those in the first complete remission at the time of BMT,

3. those who were treated with BuCy conditioning regimen, and

4. those who received bone marrow as a stem cell source.

A total of 80 patients were eligible in this study among the patients who were transplanted at the Asan Medical Center between December 1993 and July 2007: 42 patients received O-Bu (4 mg/kg/d x 4d) and 38 patients received I-Bu (Busulfex, 3.2 mg/kg/d x 4d). The same dose of cyclophosphamide (60 mg/kg/d x 2d) was given to all the patients. We collected clinical and laboratory data from the BMT database of the Asan Medical Center. The efficacy was compared in terms of cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS). Propensity score analysis was used to adjust the confounding factors between O-Bu and I-Bu groups. Several baseline clinico-laboratory factors at the time of BMT such as age, number of consolidation therapy prior to BMT, time from diagnosis to BMT, use of methotrexate for GVHD prophylaxis, and transfusion requirement before BMT were significantly different between 2 groups. Times to engraftment, transfusion requirements, infectious complications, hepatic VOD, and acute and chronic GVHD were similar between 2 groups. The cumulative incidence of non-relapse mortality was 14.3% in O-Bu group and 10.3% in I-Bu group (adjusted P-value, 0.990). The CIR at 4-year was 28.6% in O-Bu group and 16.9% in I-Bu group (adjusted P-value, 0.430). The 4-year probabilities of EFS and OS were 57.1% and 64.3% in O-Bu group and 72.6% and 69.3% in I-Bu group (adjusted P-values, 0.496 and 0.634, respectively). In summary, EFS and CIR were superior in I-Bu group compared to O-Bu group without statistical significance. Our results suggest that intravenous busulfan is as effective as oral busulfan in a conditioning therapy for BMT.