Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia

Samer Bibawi, Dima Abi-Said, Luis Fayad, Paolo Anderlini, Naoto T. Ueno, Rakesh Mehra, Issa Khouri, Sergio Giralt, James Gajewski, Michelle Donato, David Claxton, Ira Braunschweig, Koen Van Besien, Michael Andreeff, Borje S. Andersson, Elihu H. Estey, Richard Champlin, Donna Przepiorka

Research output: Contribution to journalArticle

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Abstract

Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA-matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95% Cl, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0,02). Three-year survival was 26% (95% Cl, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% transplanted for AML in relapse, and 17% with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients.

Original languageEnglish (US)
Pages (from-to)227-233
Number of pages7
JournalAmerican Journal of Hematology
Volume67
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Thiotepa
Busulfan
Myelodysplastic Syndromes
Homologous Transplantation
Acute Myeloid Leukemia
Cyclophosphamide
Mortality
Recurrence
Tissue Donors
Refractory Anemia with Excess of Blasts
Chimerism
Induction Chemotherapy
Survival
Stem Cell Transplantation
Tacrolimus
Graft vs Host Disease
Therapeutics
Cytogenetics
Blood Cells
Survival Rate

Keywords

  • Acute myelogenous leukemia
  • Allogeneic marrow transplantation
  • Myelodysplastic syndrome
  • Thiotepa

ASJC Scopus subject areas

  • Hematology

Cite this

Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia. / Bibawi, Samer; Abi-Said, Dima; Fayad, Luis; Anderlini, Paolo; Ueno, Naoto T.; Mehra, Rakesh; Khouri, Issa; Giralt, Sergio; Gajewski, James; Donato, Michelle; Claxton, David; Braunschweig, Ira; Van Besien, Koen; Andreeff, Michael; Andersson, Borje S.; Estey, Elihu H.; Champlin, Richard; Przepiorka, Donna.

In: American Journal of Hematology, Vol. 67, No. 4, 2001, p. 227-233.

Research output: Contribution to journalArticle

Bibawi, S, Abi-Said, D, Fayad, L, Anderlini, P, Ueno, NT, Mehra, R, Khouri, I, Giralt, S, Gajewski, J, Donato, M, Claxton, D, Braunschweig, I, Van Besien, K, Andreeff, M, Andersson, BS, Estey, EH, Champlin, R & Przepiorka, D 2001, 'Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia', American Journal of Hematology, vol. 67, no. 4, pp. 227-233. https://doi.org/10.1002/ajh.1121
Bibawi, Samer ; Abi-Said, Dima ; Fayad, Luis ; Anderlini, Paolo ; Ueno, Naoto T. ; Mehra, Rakesh ; Khouri, Issa ; Giralt, Sergio ; Gajewski, James ; Donato, Michelle ; Claxton, David ; Braunschweig, Ira ; Van Besien, Koen ; Andreeff, Michael ; Andersson, Borje S. ; Estey, Elihu H. ; Champlin, Richard ; Przepiorka, Donna. / Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia. In: American Journal of Hematology. 2001 ; Vol. 67, No. 4. pp. 227-233.
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abstract = "Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA-matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13{\%}) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19{\%}. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43{\%} (95{\%} Cl, 28{\%}-58{\%}). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0,02). Three-year survival was 26{\%} (95{\%} Cl, 14{\%}-37{\%}); survival rates were 29{\%} for those transplanted for AML in second remission, 31{\%} transplanted for AML in relapse, and 17{\%} with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients.",
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AU - Abi-Said, Dima

AU - Fayad, Luis

AU - Anderlini, Paolo

AU - Ueno, Naoto T.

AU - Mehra, Rakesh

AU - Khouri, Issa

AU - Giralt, Sergio

AU - Gajewski, James

AU - Donato, Michelle

AU - Claxton, David

AU - Braunschweig, Ira

AU - Van Besien, Koen

AU - Andreeff, Michael

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AU - Champlin, Richard

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