Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation

Abstract

• Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM.• The results support the use of myeloablative IV-BU vs TBIbased conditioning regimens for treatment of myeloid malignancies.We conducted a prospective cohort study testing the noninferiority of survival of ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)-based regimens in myeloid malignancies. A total of 1483 patients undergoing transplantation for myeloid malignancies (IV-BU, N 5 1025; TBI, N 5 458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease, and disease stage at transplantation. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI, 53%-60%) and 48% (95% CI, 43%-54%, P 5 .019) for IV-BU (relative risk, 0.82; 95% CI, 0.68-0.98, P 5 .03) and TBI, respectively. Corresponding incidences of transplantrelated mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI, 15%-23%, P 5 .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95% CI, 34%-44%, P 5 .08).The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression-free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM. These results support the use of myeloablative IV-BU vs TBI-based conditioning regimens for treatment of myeloid malignancies. (Blood. 2013;122(24):3871-3878)

Busulfan or TBI: answer to an age-old question

“…1,2 M yeloablative preparative regimens are designed to eradicate the leukemia and provide sufficient immunosuppression to prevent graft rejection. The optimal regimen for patients with AML is controversial.…”

“…E ndothelial cells lining arteries and veins arise from mesoderm-derived angioblasts in the embryo. 2 The common origin of these endothelial cell populations belies the fact that arteries and veins have distinct structural features, properties, and functions. The Greek anatomist Erasistratus is credited with being the first to distinguish these 2 vessel types during the third century BCE.…”

Toxicity and efficacy of busulfan and fludarabine myeloablative conditioning for HLA-identical sibling allogeneic hematopoietic cell transplantation in AML and MDS

“…Bu cohort, BuCy and BuFlu had similar NRM and OS, despite the older age of the BuFlu population. 49 Three prospective studies have specially compared BuCy with BuFlu. In a trial including 126 adults with AML, ALL or MDS, both regimens showed similar NRM and OS.…”

Acute Myeloid Leukemia in Pediatric Patients: A Review About Current Diagnostic and Treatment Approaches

“…If transplantation is chosen in pediatric AML, myeloablative chemotherapy is preferred over total body irradiation as the latter is associated with an increased risk of secondary malignancies and more late effects [82][83][84]. A large prospective CIBMTR cohort study of children and adults with AML, MDS, and CML, showed superior survival of patients in the early stages of the disease and less toxicity with busulfan-based regimens as compared to total body irradiation [85]. Despite these results, the optimal preparative regimen remains undetermined [86][87][88].…”