title: Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.
abstract: Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Division of BMT, Emory University, Atlanta, Georgia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Pasquini
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le-Rademacher
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Lill
authors.affiliation: Weill Cornell Medical Center Hematology/Oncology, The New York Hospital, New York, New York.
authors.forename: Tsiporah B
authors.initials: TB
authors.lastname: Shore
authors.affiliation: Bone Marrow Transplantation Program, University of Alabaman at Birmingham, Birmingham, Alabama.
authors.forename: William
authors.initials: W
authors.lastname: Vaughan
authors.affiliation: West Virginia University, Health Science Center, Morgantown, West Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Craig
authors.affiliation: South Texas Veterans Health Care System, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Cesar O
authors.initials: CO
authors.lastname: Freytes
authors.affiliation: Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.affiliation: Baylor University Medical Center, Dallas, Texas.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Fay
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Shin
authors.initials: S
authors.lastname: Mineishi
authors.affiliation: Department of Medicine, Section of Hematology-Oncology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rondelli
authors.affiliation: Scripps Clinic, La Jolla, California.
authors.forename: James
authors.initials: J
authors.lastname: Mason
authors.affiliation: Department of Oncology, Montefiore Medical Center, Bronx, New York.
authors.forename: Ira
authors.initials: I
authors.lastname: Braunschweig
authors.affiliation: Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Ai
authors.affiliation: Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Rosa F
authors.initials: RF
authors.lastname: Yeh
authors.affiliation: Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois.
authors.forename: Tulio E
authors.initials: TE
authors.lastname: Rodriguez
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.
authors.forename: Ian
authors.initials: I
authors.lastname: Flinn
authors.affiliation: New Brunswick Stem Cell Transplant Program, St. John, New Brunswick, Canada.
authors.forename: Terrance
authors.initials: T
authors.lastname: Comeau
authors.affiliation: Blood and Marrow Transplantation Program, The University of Arizona Cancer Center, Tucson, Arizona.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Yeager
authors.affiliation: Division of Hematology, Oncology, and Blood and Marrow Transplant, Children's Hospital Los Angeles, Keck School of Medicine and University of Southern California, Los Angeles, California.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: The University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bence-Bruckler
authors.affiliation: Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laneuville
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Philip
authors.initials: P
authors.lastname: Bierman
authors.affiliation: Center for Hematologic Malignancies, Oregon Health & Science University, Portland, Oregon.
authors.forename: Andy I
authors.initials: AI
authors.lastname: Chen
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Kato
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey.
authors.forename: Cong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Division of BMT, Emory University, Atlanta, Georgia. Electronic address: ewaller@emory.edu.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002330:Carmustine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use; D004338:Drug Combinations; D005047:Etoposide / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009656:North America; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014182:Transplantation, Autologous
chemical_list: D004338:Drug Combinations; D003561:Cytarabine; D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan; D002330:Carmustine
keywords: Autologous stem cell transplantation; Busulfan; Chemotherapy; Hodgkin lymphoma; Lymphoma; Non-Hodgkin lymphoma; Stem cell transplantation