title: Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies.
abstract: Busulfan (Bu)-containing regimens are commonly used in myeloablative conditioning regimens before allogeneic hematopoietic cell transplantation (HCT). Yet, there is considerable variability on how Bu is administered related to frequency (4 times a day [Q6] or daily [Q24]) and combinations with other chemotherapeutic agents (cyclophosphamide [Cy] or fludarabine [Flu]). We performed a prospective cohort study of recipients of Bu-based conditioning according to contemporary practices to compare different approaches (BuCy Q6, n = 495; BuFlu Q24, n = 331; BuCy Q24, n = 96; BuFlu Q6, n = 91) in patients with myeloid malignancies between 2009 and 2011. BuFlu Q24 recipients were more likely to be older and tended to have worse performance status and a higher comorbid burden. The cumulative incidences of hepatic veno-occlusive disease (P = .40), idiopathic pneumonia (P = .50), and seizures (P = .50) did not differ across groups. One-year HCT-related mortality ranged from 12% to 16% (P = .80), 3-year relapse incidence ranged from 32% to 36% (P = .80), and 3-year overall survival ranged from 51% to 58% (P = .20) across groups. This study demonstrates that HCT conditioning regimens using i.v. Bu Q6 or Q24 alone or in combination with Cy or Flu have similar outcomes in the myeloablative setting for treatment of myeloid malignancies.
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: mpasquini@mcw.edu.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Pasquini
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le-Rademacher
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Section of Hematology/Oncology, University of Chicago School of Medicine, Chicago, Illinois.
authors.forename: Andrew
authors.initials: A
authors.lastname: Artz
authors.affiliation: Department of Hematology/Oncology, Barnes Jewish Hospital, St. Louis, Missouri.
authors.forename: John
authors.initials: J
authors.lastname: DiPersio
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Fernandez
authors.affiliation: Bone Marrow Transplant Program, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Shin
authors.initials: S
authors.lastname: Mineishi
authors.affiliation: Otsuka Pharmaceutical Co, Ltd, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kamishohara
authors.affiliation: Department of Hematology/ Oncology, Northwestern Memorial Hospital, Chicago, Illinois.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Mehta
authors.affiliation: Otsuka Pharmaceutical Co, Ltd, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Clinical Arrangements, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan; J.P. McCarthy Cord Stem Cell Bank, Detroit, Michigan.
authors.forename: Voravit
authors.initials: V
authors.lastname: Ratanatharathorn
authors.affiliation: Department of Hematopoietic Oncology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Burkart
authors.affiliation: The Ottawa Hospital Blood and Marrow Transplant Program and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011014:Pneumonia / Q000209:etiology; D011446:Prospective Studies; D012640:Seizures / Q000209:etiology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Busulfan; Fludarabine; Myeloablative