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 Flinn & 12 others Terrance 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

7 Citations (Scopus)

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
StatePublished - Jul 1 2016

Fingerprint

Busulfan
Stem Cell Transplantation
Etoposide
Cyclophosphamide
Hodgkin Disease
Lymphoma
Pharmacokinetics
Outcome Assessment (Health Care)
Non-Hodgkin's Lymphoma
Disease-Free Survival
Mortality
Safety
Mantle-Cell Lymphoma
Carmustine
Follicular Lymphoma
Melphalan
Survival
Lymphoma, Large B-Cell, Diffuse
Cytarabine
B-Cell Lymphoma

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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

In: Biology of Blood and Marrow Transplantation, Vol. 22, No. 7, 01.07.2016, p. 1197-1205.

Research output: Contribution to journalArticle

Flowers, CR, Costa, LJ, Pasquini, MC, Le-Rademacher, J, Lill, M, Shore, TB, Vaughan, W, Craig, M, Freytes, CO, Shea, TC, Horwitz, ME, Fay, JW, Mineishi, S, Rondelli, D, Mason, J, Braunschweig, I, Ai, W, Yeh, RF, Rodriguez, TE, Flinn, I, Comeau, T, Yeager, AM, Pulsipher, MA, Bence-Bruckler, I, Laneuville, P, Bierman, PJ, Chen, AI, Kato, K, Wang, Y, Xu, C, Smith, AJ & Waller, EK 2016, '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', Biology of Blood and Marrow Transplantation, vol. 22, no. 7, pp. 1197-1205. https://doi.org/10.1016/j.bbmt.2016.03.018
Flowers, Christopher R. ; Costa, Luciano J. ; Pasquini, Marcelo C. ; Le-Rademacher, Jennifer ; Lill, Michael ; Shore, Tsiporah B. ; Vaughan, William ; Craig, Michael ; Freytes, Cesar O. ; Shea, Thomas C. ; Horwitz, Mitchell E. ; Fay, Joseph W. ; Mineishi, Shin ; Rondelli, Damiano ; Mason, James ; Braunschweig, Ira ; Ai, Weiyun ; Yeh, Rosa F. ; Rodriguez, Tulio E. ; Flinn, Ian ; Comeau, Terrance ; Yeager, Andrew M. ; Pulsipher, Michael A. ; Bence-Bruckler, Isabelle ; Laneuville, Pierre ; Bierman, Philip Jay ; Chen, Andy I. ; Kato, Kazunobu ; Wang, Yanlin ; Xu, Cong ; Smith, Angela J. ; Waller, Edmund K. / 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. In: Biology of Blood and Marrow Transplantation. 2016 ; Vol. 22, No. 7. pp. 1197-1205.
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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.",
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T1 - Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma

T2 - Comparison of a Multicenter Phase II Study and CIBMTR Outcomes

AU - Flowers, Christopher R.

AU - Costa, Luciano J.

AU - Pasquini, Marcelo C.

AU - Le-Rademacher, Jennifer

AU - Lill, Michael

AU - Shore, Tsiporah B.

AU - Vaughan, William

AU - Craig, Michael

AU - Freytes, Cesar O.

AU - Shea, Thomas C.

AU - Horwitz, Mitchell E.

AU - Fay, Joseph W.

AU - Mineishi, Shin

AU - Rondelli, Damiano

AU - Mason, James

AU - Braunschweig, Ira

AU - Ai, Weiyun

AU - Yeh, Rosa F.

AU - Rodriguez, Tulio E.

AU - Flinn, Ian

AU - Comeau, Terrance

AU - Yeager, Andrew M.

AU - Pulsipher, Michael A.

AU - Bence-Bruckler, Isabelle

AU - Laneuville, Pierre

AU - Bierman, Philip Jay

AU - Chen, Andy I.

AU - Kato, Kazunobu

AU - Wang, Yanlin

AU - Xu, Cong

AU - Smith, Angela J.

AU - Waller, Edmund K.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

KW - Autologous stem cell transplantation

KW - Busulfan

KW - Chemotherapy

KW - Hodgkin lymphoma

KW - Lymphoma

KW - Non-Hodgkin lymphoma

KW - Stem cell transplantation

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