title: High-dose busulfan, cyclophosphamide, and etoposide does not improve outcome of allogeneic stem cell transplantation compared to BuCy2 in patients with acute myeloid leukemia.
abstract: To reduce relapse following allogeneic transplantation for AML, intensification of high-dose busulfan/cyclophosphamide using additional agents has been investigated but with few reported comparisons. We compared an intensified regimen of etoposide (60 mg/kg), busulphan (14 mg/kg), and cyclophosphamide (120 mg/kg) (BuCyVP) with BuCy2 in 237 AML patients. No significant difference in overall outcome was observed following BuCyVP (n=127) or BuCy2 (n=110). The 5-year survival was 27.3 and 30.1% following BuCyVP and BuCy2, respectively (P=0.48). Similarly, the 5-year cumulative incidence of relapse (CIR) was 28.3 and 34.8% with BuCyVP and BuCy2 (P=0.45), respectively. On multivariable analysis, patients transplanted in CR1 (P=0.002) and from related donors (P=0.013) had longer survival, while disease status at transplant was the only factor predicting CIR (P=0.002). In a separate analysis of CR1 patients (n=56), there was no significant difference in survival (P=0.37) or CIR (P=0.87) between the two regimens. However, for more advanced disease, there was a trend towards less relapse with BuCyVP (P=0.08), which was balanced by a higher cumulative incidence of transplant-related deaths (P=0.03) compared to BuCy2, resulting in similar survival. Overall, our results do not support the use of the more intensive BuCyVP regimen over BuCy2 in either early or more advanced disease AML patients.
authors.affiliation: Hematologic Malignancies Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. farag-1@medctr.osu.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Farag
authors.forename: B J
authors.initials: BJ
authors.lastname: Bolwell
authors.forename: P J
authors.initials: PJ
authors.lastname: Elder
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
authors.forename: T
authors.initials: T
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Pohlman
authors.forename: S
authors.initials: S
authors.lastname: Penza
authors.forename: G
authors.initials: G
authors.lastname: Marcucci
authors.forename: W
authors.initials: W
authors.lastname: Blum
authors.forename: R
authors.initials: R
authors.lastname: Sobecks
authors.forename: B R
authors.initials: BR
authors.lastname: Avalos
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.forename: E
authors.initials: E
authors.lastname: Copelan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage; D002423:Cause of Death; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007951:Leukemia, Myeloid / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan