Intravenous Verses Oral Busulfan With Cyclophosphamide for Allogeneic Hematopoietic Progenitor Cell Transplant Conditioning for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

ORLANDO, Fla.—A study by Ronald Sobecks, MD, and colleagues at the Cleveland Clinic in Cleveland, Ohio, has been found that using IV busulfan (Bu) instead of oral Bu reduces variability in drug exposure and potentially improves safety.

Bu is commonly used in combination with cyclophosphamide (Cy) as a conditioning regimen for allogeneic hematopoietic progenitor cell transplantation (HPCT). A previous study showed that substituting IV Bu for oral is associated with a lower rate of relapse, and superior relapse-free and overall survivals for relapsed or refractory non-Hodgkin’s lymphoma patients undergoing autologous HPCT (Dean et al. Br J Haematol. 2010 Jan;148(2)226-34).

The findings from this retrospective study were presented at the 52nd American Society of Hematology Meeting and Exposition. This analysis evaluated 135 consecutively treated patients with AML and MDS who underwent allogeneic HPCT at the Cleveland Clinic. Ninety-three patients were treated with oral Bu plus cyclophosphamide (Cy) and 42 patients with IV Bu plus Cy. The analysis included matched related donors (n=97) and 8/8 HLA matched unrelated donors (n=38). Patients receiving oral Bu were administered 1 mg/kg every 6 hours for 16 doses and those administered IV Bu received 0.8 mg/kg every 6 hours for 16 doses. All patients received Cy at a dose of 60 mg/kg/day for 2 days following treatment with Bu. Patient demographics were similar between both treatment arms, except that patients in the IV Bu group were older (median age, 49 vs 47 years, respectively, P=0.037), and more commonly had unrelated donors and peripheral blood stem cells for their HPCT cell source than those treated with oral Bu.

Results from the study showed those patients receiving IV Bu experienced significantly lower incidence of mucositis (3% vs 55%, P<0.001) and less severe mucositis (P<0.001). No significant differences were found in days until neutrophil and platelet count engraftment, length of transplant hospitalization, incidence of acute or chronic GVHD, sinusoidal obstruction syndrome, and 100-day mortality.

Currently, 26 (62%) of the patients treated with IV Bu and 33 (36%) patients treated with oral Bu are alive. However, median follow-up was longer for the oral Bu group (50 vs 13 months, P<0.001). The most common cause of death in both treatment arms was disease relapse. Transplant-related mortality in the IV Bu group at 1 and 2 years was 21% for both. For the oral Bu group, transplant-related mortality at 1 and 2 years was 23% and 29%, respectively.

The results of this study show that IV Bu reduces variability in drug exposure and potentially improves safety compared with oral Bu. However, additional follow-up of those patients treated with IV Bu is required to adequately assess for a survival benefit. In addition, it may be worthwhile to study whether pharmacokinetic-based Bu dosing can improve outcomes after allogeneic HPCT.