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Author Notes:

Corresponding Author: Edmund K. Waller MD, PhD, FACP, 1365B Clifton Road Suite B5119, Winship Cancer Institute, Emory University, Atlanta, GA, USA, Phone: 404-727-4996; Fax: 404-778-5530, ewaller@emory.edu

The authors thank the patients, their caregivers and the staff at participating centers.

We also thank Louie Yu and Shiva Patil for pharmacokinetic support, Jeanne Burkart for registry support, Agnes Elekes for medical review, and Cathy Zhao and Peter Loonan for statistical analysis.

The authors also thank David Norris, PhD, for editorial assistance provided during the preparation of this report.

Christopher R. Flowers, Luciano J. Costa, Marcelo C. Pasquini, Jennifer Le-Rademacher, Michael Lill, Tsiporah B. Shore, William Vaughan, Michael Craig, Thomas C. Shea, Mitchell E. Horwitz, Joseph W. Fay, Ira Braunschweig, Weiyun Ai, Rosa F. Yeh, Tulio E. Rodriguez, Ian Flinn, Andrew M. Yeager, Michael A. Pulsipher, Isabelle Bence-Bruckler, Pierre Laneuville, Philip Bierman, and Andy I. Chen declare no financial conflicts of interest for this study.

Cesar O. Freytes has received grant/research support from Otsuka and Merck, is a consultant to Otsuka and Clinipace, and serves on the speakers bureau for Sanofi and advisory boards for Spectrum Pharmaceutical.

Shin Mineishi has received research support from Otsuka for an unrelated subject.

Damiano Rondelli has received honoraria for advisory boards and speaker bureaus from Sanofi and a research grant from Otsuka.

James Mason serves as a consultant to Pfizer and Genoptix.

Terrance Comeau serves on advisory boards for Celgene, Johnson & Johnson and Lundbek.

Kazunobu Kato, Yanlin Wang, Cong Xu and Angela Smith have been, or are currently, employees of Otsuka Pharmaceutical Development & Commercialization, Inc. Edmund K. Waller has served as a consultant to Otsuka.

Subjects:

Research Funding:

This assistance was paid for through funding supplied by OPDC to Ecosse Medical Communications, LLC (Falmouth, MA).

Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) sponsored this study and provided the intravenous busulfan for the analyses.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • Immunology
  • Transplantation
  • Non-Hodgkin lymphoma
  • Hodgkin lymphoma
  • Busulfan
  • Autologous stem cell transplantation
  • Stem cell transplantation
  • Lymphoma
  • Chemotherapy
  • HIGH-DOSE CHEMOTHERAPY
  • NON-HODGKINS-LYMPHOMA
  • BONE-MARROW-TRANSPLANTATION
  • DAILY INTRAVENOUS BUSULFAN
  • HIGH-RISK PATIENTS
  • DAILY IV BUSULFAN
  • PREPARATIVE REGIMENS
  • AGGRESSIVE LYMPHOMA
  • BEAM CHEMOTHERAPY
  • RANDOMIZED-TRIAL

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

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Journal Title:

Biology of Blood and Marrow Transplantation

Volume:

Volume 22, Number 7

Publisher:

, Pages 1197-1205

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2016 American Society for Blood and Marrow Transplantation.

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