title: Superior survival after replacing oral with intravenous busulfan in autologous stem cell transplantation for non-Hodgkin lymphoma with busulfan, cyclophosphamide and etoposide.
abstract: Autologous stem cell transplantation (ASCT) with cyclophosphamide, etoposide and oral busulfan (BuCyVP) is an effective therapy for relapsed or refractory non-Hodgkin lymphoma (NHL). Substituting intravenous for oral busulfan reduces variability in drug exposure, potentially improving the safety and efficacy of the BuCyVP regimen. We retrospectively compared the outcomes of 604 consecutively treated patients who underwent ASCT for NHL with BuCyVP using oral (n = 468) or IV (n = 136) busulfan, without measurement of busulfan levels for pharmacokinetic (PK) analysis. Patients who received oral busulfan experienced more severe oral mucositis and a higher incidence of nonrelapse mortality. Median overall survival (OS) after ASCT was 72 months with oral busulfan but was not reached for the IV busulfan group. IV busulfan was associated with a lower rate of relapse, and superior relapse-free survival (RFS) and OS. In multivariate models, the route of busulfan administration was an independent prognostic factor for relapse (P = 0.01), RFS (P = 0.002) and OS (P = 0.001). IV busulfan appears to provide better efficacy and lower toxicity than oral busulfan in ASCT with BuCyVP for NHL. Whether PK-based busulfan dosing can achieve further improvements in this setting is worthy of study.
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic, OH 44195, USA. deanr@ccf.org
authors.forename: Robert M
authors.initials: RM
authors.lastname: Dean
authors.forename: Brad
authors.initials: B
authors.lastname: Pohlman
authors.forename: John W
authors.initials: JW
authors.lastname: Sweetenham
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Sobecks
authors.forename: Matt E
authors.initials: ME
authors.lastname: Kalaycio
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Smith
authors.forename: Edward A
authors.initials: EA
authors.lastname: Copelan
authors.forename: Steven
authors.initials: S
authors.lastname: Andresen
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
authors.forename: Julie
authors.initials: J
authors.lastname: Curtis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bolwell
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007275:Injections, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D019653:Myeloablative Agonists; D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan