Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: An intensive regimen for the treatment of multiple myeloma

A. Shimoni, T. L. Smith, A. Aleman, D. Weber, M. Dimopoulos, P. Anderlini, B. Andersson, D. Claxton, N. T. Ueno, I. Khouri, M. Donato, M. Korbling, R. Alexanian, R. Champlin, S. Giralt

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Abstract

The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.

Original languageEnglish (US)
Pages (from-to)821-828
Number of pages8
JournalBone Marrow Transplantation
Volume27
Issue number8
DOIs
StatePublished - Jun 12 2001

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Thiotepa
Busulfan
Autologous Transplantation
Multiple Myeloma
Cyclophosphamide
Therapeutics
Transplants
Survival
Peripheral Blood Stem Cell Transplantation
Alkylating Agents
Cell Transplantation
Statistical Factor Analysis
Transplantation
Bone Marrow
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Shimoni, A. ; Smith, T. L. ; Aleman, A. ; Weber, D. ; Dimopoulos, M. ; Anderlini, P. ; Andersson, B. ; Claxton, D. ; Ueno, N. T. ; Khouri, I. ; Donato, M. ; Korbling, M. ; Alexanian, R. ; Champlin, R. ; Giralt, S. / Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation : An intensive regimen for the treatment of multiple myeloma. In: Bone Marrow Transplantation. 2001 ; Vol. 27, No. 8. pp. 821-828.
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title = "Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: An intensive regimen for the treatment of multiple myeloma",
abstract = "The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81{\%} and the complete remission (CR) rate was 26{\%}. Patients with chemosensitive disease had a CR rate of 52{\%} vs 5{\%} for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8{\%}. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.",
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Shimoni, A, Smith, TL, Aleman, A, Weber, D, Dimopoulos, M, Anderlini, P, Andersson, B, Claxton, D, Ueno, NT, Khouri, I, Donato, M, Korbling, M, Alexanian, R, Champlin, R & Giralt, S 2001, 'Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: An intensive regimen for the treatment of multiple myeloma', Bone Marrow Transplantation, vol. 27, no. 8, pp. 821-828. https://doi.org/10.1038/sj.bmt.1703007

Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation : An intensive regimen for the treatment of multiple myeloma. / Shimoni, A.; Smith, T. L.; Aleman, A.; Weber, D.; Dimopoulos, M.; Anderlini, P.; Andersson, B.; Claxton, D.; Ueno, N. T.; Khouri, I.; Donato, M.; Korbling, M.; Alexanian, R.; Champlin, R.; Giralt, S.

In: Bone Marrow Transplantation, Vol. 27, No. 8, 12.06.2001, p. 821-828.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation

T2 - An intensive regimen for the treatment of multiple myeloma

AU - Shimoni, A.

AU - Smith, T. L.

AU - Aleman, A.

AU - Weber, D.

AU - Dimopoulos, M.

AU - Anderlini, P.

AU - Andersson, B.

AU - Claxton, D.

AU - Ueno, N. T.

AU - Khouri, I.

AU - Donato, M.

AU - Korbling, M.

AU - Alexanian, R.

AU - Champlin, R.

AU - Giralt, S.

PY - 2001/6/12

Y1 - 2001/6/12

N2 - The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.

AB - The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.

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