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

Christopher R. Flowers, Luciano J. Costa, Marcelo C. Pasquini, Jennifer Le-Rademacher, Michael Lill, Tsiporah B. Shore, William Vaughan, Michael Craig, Cesar O. Freytes, Thomas C. Shea, Mitchell E. Horwitz, Joseph W. Fay, Shin Mineishi, Damiano Rondelli, James Mason, Ira Braunschweig, Weiyun Ai, Rosa F. Yeh, Tulio E. Rodriguez, Ian FlinnTerrance Comeau, Andrew M. Yeager, Michael A. Pulsipher, Isabelle Bence-Bruckler, Pierre Laneuville, Philip Jay Bierman, Andy I. Chen, Kazunobu Kato, Yanlin Wang, Cong Xu, Angela J. Smith, Edmund K. Waller

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1197-1205
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

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Keywords

  • Autologous stem cell transplantation
  • Busulfan
  • Chemotherapy
  • Hodgkin lymphoma
  • Lymphoma
  • Non-Hodgkin lymphoma
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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