Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

Renato Bassan, Tamara Intermesoli, Arianna Masciulli, Chiara Pavoni, Cristina Boschini, Giacomo Gianfaldoni, Filippo Marmont, Irene Cavattoni, Daniele Mattei, Elisabetta Terruzzi, Lorella De Paoli, Chiara Cattaneo, Erika Borlenghi, Fabio Ciceri, Massimo Bernardi, Anna M. Scattolin, Elisabetta Todisco, Leonardo Campiotti, Paolo Corradini, Agostino CortelezziDario Ferrero, Pamela Zanghì, Elena Oldani, Orietta Spinelli, Ernesta Audisio, Sergio Cortelazzo, Alberto Bosi, Brunangelo Falini, Enrico M. Pogliani, Alessandro Rambaldi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n 5 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n 5 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P 5 .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P 5 .0007) with lower resistance risk (P, .0001), comparable mortality (P 5 .39), and improved 5-year overall survival (39% vs 49%; P 5 .045) and relapse-free survival (36% vs 48%; P 5 .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P 5 .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P 5 .003), and also improved overall/ relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P 5 .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P 5 .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.

Original languageEnglish
Pages (from-to)1103-1117
Number of pages15
JournalBlood advances
Volume3
Issue number7
DOIs
Publication statusPublished - Apr 9 2019

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Acute Myeloid Leukemia
Idarubicin
Drug Therapy
Cytarabine
Etoposide
Confidence Intervals
Survival
Stem Cells
Odds Ratio
Remission Induction
Recurrence
Autografts
Random Allocation
Blood Cells
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bassan, R., Intermesoli, T., Masciulli, A., Pavoni, C., Boschini, C., Gianfaldoni, G., ... Rambaldi, A. (2019). Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood advances, 3(7), 1103-1117. https://doi.org/10.1182/bloodadvances.2018026625

Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. / Bassan, Renato; Intermesoli, Tamara; Masciulli, Arianna; Pavoni, Chiara; Boschini, Cristina; Gianfaldoni, Giacomo; Marmont, Filippo; Cavattoni, Irene; Mattei, Daniele; Terruzzi, Elisabetta; De Paoli, Lorella; Cattaneo, Chiara; Borlenghi, Erika; Ciceri, Fabio; Bernardi, Massimo; Scattolin, Anna M.; Todisco, Elisabetta; Campiotti, Leonardo; Corradini, Paolo; Cortelezzi, Agostino; Ferrero, Dario; Zanghì, Pamela; Oldani, Elena; Spinelli, Orietta; Audisio, Ernesta; Cortelazzo, Sergio; Bosi, Alberto; Falini, Brunangelo; Pogliani, Enrico M.; Rambaldi, Alessandro.

In: Blood advances, Vol. 3, No. 7, 09.04.2019, p. 1103-1117.

Research output: Contribution to journalArticle

Bassan, R, Intermesoli, T, Masciulli, A, Pavoni, C, Boschini, C, Gianfaldoni, G, Marmont, F, Cavattoni, I, Mattei, D, Terruzzi, E, De Paoli, L, Cattaneo, C, Borlenghi, E, Ciceri, F, Bernardi, M, Scattolin, AM, Todisco, E, Campiotti, L, Corradini, P, Cortelezzi, A, Ferrero, D, Zanghì, P, Oldani, E, Spinelli, O, Audisio, E, Cortelazzo, S, Bosi, A, Falini, B, Pogliani, EM & Rambaldi, A 2019, 'Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML', Blood advances, vol. 3, no. 7, pp. 1103-1117. https://doi.org/10.1182/bloodadvances.2018026625
Bassan, Renato ; Intermesoli, Tamara ; Masciulli, Arianna ; Pavoni, Chiara ; Boschini, Cristina ; Gianfaldoni, Giacomo ; Marmont, Filippo ; Cavattoni, Irene ; Mattei, Daniele ; Terruzzi, Elisabetta ; De Paoli, Lorella ; Cattaneo, Chiara ; Borlenghi, Erika ; Ciceri, Fabio ; Bernardi, Massimo ; Scattolin, Anna M. ; Todisco, Elisabetta ; Campiotti, Leonardo ; Corradini, Paolo ; Cortelezzi, Agostino ; Ferrero, Dario ; Zanghì, Pamela ; Oldani, Elena ; Spinelli, Orietta ; Audisio, Ernesta ; Cortelazzo, Sergio ; Bosi, Alberto ; Falini, Brunangelo ; Pogliani, Enrico M. ; Rambaldi, Alessandro. / Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. In: Blood advances. 2019 ; Vol. 3, No. 7. pp. 1103-1117.
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abstract = "Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n 5 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n 5 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8{\%}) and sHD (83.6{\%}; P 5 .38). sHD yielded a higher single-induction CR rate (69.2{\%} vs 81.5{\%}; P 5 .0007) with lower resistance risk (P, .0001), comparable mortality (P 5 .39), and improved 5-year overall survival (39{\%} vs 49{\%}; P 5 .045) and relapse-free survival (36{\%} vs 48{\%}; P 5 .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95{\%} confidence interval [CI], 0.31-0.74; P 5 .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95{\%} CI, 0.27-0.78; P 5 .003), and also improved overall/ relapse-free survival in the latter group (hazard ratio, 0.70; 95{\%} CI, 0.52-0.94; P 5 .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95{\%} CI, 0.39-0.96; P 5 .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.",
author = "Renato Bassan and Tamara Intermesoli and Arianna Masciulli and Chiara Pavoni and Cristina Boschini and Giacomo Gianfaldoni and Filippo Marmont and Irene Cavattoni and Daniele Mattei and Elisabetta Terruzzi and {De Paoli}, Lorella and Chiara Cattaneo and Erika Borlenghi and Fabio Ciceri and Massimo Bernardi and Scattolin, {Anna M.} and Elisabetta Todisco and Leonardo Campiotti and Paolo Corradini and Agostino Cortelezzi and Dario Ferrero and Pamela Zangh{\`i} and Elena Oldani and Orietta Spinelli and Ernesta Audisio and Sergio Cortelazzo and Alberto Bosi and Brunangelo Falini and Pogliani, {Enrico M.} and Alessandro Rambaldi",
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T1 - Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

AU - Bassan, Renato

AU - Intermesoli, Tamara

AU - Masciulli, Arianna

AU - Pavoni, Chiara

AU - Boschini, Cristina

AU - Gianfaldoni, Giacomo

AU - Marmont, Filippo

AU - Cavattoni, Irene

AU - Mattei, Daniele

AU - Terruzzi, Elisabetta

AU - De Paoli, Lorella

AU - Cattaneo, Chiara

AU - Borlenghi, Erika

AU - Ciceri, Fabio

AU - Bernardi, Massimo

AU - Scattolin, Anna M.

AU - Todisco, Elisabetta

AU - Campiotti, Leonardo

AU - Corradini, Paolo

AU - Cortelezzi, Agostino

AU - Ferrero, Dario

AU - Zanghì, Pamela

AU - Oldani, Elena

AU - Spinelli, Orietta

AU - Audisio, Ernesta

AU - Cortelazzo, Sergio

AU - Bosi, Alberto

AU - Falini, Brunangelo

AU - Pogliani, Enrico M.

AU - Rambaldi, Alessandro

PY - 2019/4/9

Y1 - 2019/4/9

N2 - Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n 5 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n 5 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P 5 .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P 5 .0007) with lower resistance risk (P, .0001), comparable mortality (P 5 .39), and improved 5-year overall survival (39% vs 49%; P 5 .045) and relapse-free survival (36% vs 48%; P 5 .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P 5 .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P 5 .003), and also improved overall/ relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P 5 .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P 5 .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.

AB - Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n 5 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n 5 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P 5 .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P 5 .0007) with lower resistance risk (P, .0001), comparable mortality (P 5 .39), and improved 5-year overall survival (39% vs 49%; P 5 .045) and relapse-free survival (36% vs 48%; P 5 .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P 5 .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P 5 .003), and also improved overall/ relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P 5 .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P 5 .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.

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