Dexamethasone vs prednisone in induction treatment of pediatric ALL

results of the randomized trial AIEOP-BFM ALL 2000

Anja Möricke, Martin Zimmermann, Maria Grazia Valsecchi, Martin Stanulla, Andrea Biondi, Georg Mann, Franco Locatelli, Giovanni Cazzaniga, Felix Niggli, Maurizio Aricò, Claus R. Bartram, Andishe Attarbaschi, Daniela Silvestri, Rita Beier, Giuseppe Basso, Richard Ratei, Andreas E. Kulozik, Luca Lo Nigro, Bernhard Kremens, Jeanette Greiner & 8 others Rosanna Parasole, Jochen Harbott, Roberta Caruso, Arend von Stackelberg, Elena Barisone, Claudia Rössig, Valentino Conter, Martin Schrappe

Research output: Contribution to journalArticle

Abstract

Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7% in the dexamethasone and 15.6 ± 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9% for dexamethasone and 80.8 ± 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7%; prednisone, 90.5 ± 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4%; prednisone, 82.6 ± 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457).

Original languageEnglish
Pages (from-to)2101-12
Number of pages12
JournalBlood
Volume127
Issue number17
DOIs
Publication statusPublished - Apr 28 2016

Fingerprint

Pediatrics
Berlin
Prednisone
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Dexamethasone
Recurrence
Survival
Therapeutics
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
T-cells
Cells
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Incidence
T-Lymphocyte Subsets
Disease-Free Survival
Survival Rate

Keywords

  • Journal Article

Cite this

Möricke, A., Zimmermann, M., Valsecchi, M. G., Stanulla, M., Biondi, A., Mann, G., ... Schrappe, M. (2016). Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood, 127(17), 2101-12. https://doi.org/10.1182/blood-2015-09-670729

Dexamethasone vs prednisone in induction treatment of pediatric ALL : results of the randomized trial AIEOP-BFM ALL 2000. / Möricke, Anja; Zimmermann, Martin; Valsecchi, Maria Grazia; Stanulla, Martin; Biondi, Andrea; Mann, Georg; Locatelli, Franco; Cazzaniga, Giovanni; Niggli, Felix; Aricò, Maurizio; Bartram, Claus R.; Attarbaschi, Andishe; Silvestri, Daniela; Beier, Rita; Basso, Giuseppe; Ratei, Richard; Kulozik, Andreas E.; Nigro, Luca Lo; Kremens, Bernhard; Greiner, Jeanette; Parasole, Rosanna; Harbott, Jochen; Caruso, Roberta; von Stackelberg, Arend; Barisone, Elena; Rössig, Claudia; Conter, Valentino; Schrappe, Martin.

In: Blood, Vol. 127, No. 17, 28.04.2016, p. 2101-12.

Research output: Contribution to journalArticle

Möricke, A, Zimmermann, M, Valsecchi, MG, Stanulla, M, Biondi, A, Mann, G, Locatelli, F, Cazzaniga, G, Niggli, F, Aricò, M, Bartram, CR, Attarbaschi, A, Silvestri, D, Beier, R, Basso, G, Ratei, R, Kulozik, AE, Nigro, LL, Kremens, B, Greiner, J, Parasole, R, Harbott, J, Caruso, R, von Stackelberg, A, Barisone, E, Rössig, C, Conter, V & Schrappe, M 2016, 'Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000', Blood, vol. 127, no. 17, pp. 2101-12. https://doi.org/10.1182/blood-2015-09-670729
Möricke, Anja ; Zimmermann, Martin ; Valsecchi, Maria Grazia ; Stanulla, Martin ; Biondi, Andrea ; Mann, Georg ; Locatelli, Franco ; Cazzaniga, Giovanni ; Niggli, Felix ; Aricò, Maurizio ; Bartram, Claus R. ; Attarbaschi, Andishe ; Silvestri, Daniela ; Beier, Rita ; Basso, Giuseppe ; Ratei, Richard ; Kulozik, Andreas E. ; Nigro, Luca Lo ; Kremens, Bernhard ; Greiner, Jeanette ; Parasole, Rosanna ; Harbott, Jochen ; Caruso, Roberta ; von Stackelberg, Arend ; Barisone, Elena ; Rössig, Claudia ; Conter, Valentino ; Schrappe, Martin. / Dexamethasone vs prednisone in induction treatment of pediatric ALL : results of the randomized trial AIEOP-BFM ALL 2000. In: Blood. 2016 ; Vol. 127, No. 17. pp. 2101-12.
@article{68f00c62f6a74ad8bf0d0702e12c21d3,
title = "Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000",
abstract = "Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-M{\"u}nster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7{\%} in the dexamethasone and 15.6 ± 0.8{\%} in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5{\%} vs 0.9{\%}, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9{\%} for dexamethasone and 80.8 ± 0.9{\%} for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7{\%}; prednisone, 90.5 ± 0.7{\%}). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4{\%}; prednisone, 82.6 ± 3.2{\%}; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457).",
keywords = "Journal Article",
author = "Anja M{\"o}ricke and Martin Zimmermann and Valsecchi, {Maria Grazia} and Martin Stanulla and Andrea Biondi and Georg Mann and Franco Locatelli and Giovanni Cazzaniga and Felix Niggli and Maurizio Aric{\`o} and Bartram, {Claus R.} and Andishe Attarbaschi and Daniela Silvestri and Rita Beier and Giuseppe Basso and Richard Ratei and Kulozik, {Andreas E.} and Nigro, {Luca Lo} and Bernhard Kremens and Jeanette Greiner and Rosanna Parasole and Jochen Harbott and Roberta Caruso and {von Stackelberg}, Arend and Elena Barisone and Claudia R{\"o}ssig and Valentino Conter and Martin Schrappe",
note = "{\circledC} 2016 by The American Society of Hematology.",
year = "2016",
month = "4",
day = "28",
doi = "10.1182/blood-2015-09-670729",
language = "English",
volume = "127",
pages = "2101--12",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "17",

}

TY - JOUR

T1 - Dexamethasone vs prednisone in induction treatment of pediatric ALL

T2 - results of the randomized trial AIEOP-BFM ALL 2000

AU - Möricke, Anja

AU - Zimmermann, Martin

AU - Valsecchi, Maria Grazia

AU - Stanulla, Martin

AU - Biondi, Andrea

AU - Mann, Georg

AU - Locatelli, Franco

AU - Cazzaniga, Giovanni

AU - Niggli, Felix

AU - Aricò, Maurizio

AU - Bartram, Claus R.

AU - Attarbaschi, Andishe

AU - Silvestri, Daniela

AU - Beier, Rita

AU - Basso, Giuseppe

AU - Ratei, Richard

AU - Kulozik, Andreas E.

AU - Nigro, Luca Lo

AU - Kremens, Bernhard

AU - Greiner, Jeanette

AU - Parasole, Rosanna

AU - Harbott, Jochen

AU - Caruso, Roberta

AU - von Stackelberg, Arend

AU - Barisone, Elena

AU - Rössig, Claudia

AU - Conter, Valentino

AU - Schrappe, Martin

N1 - © 2016 by The American Society of Hematology.

PY - 2016/4/28

Y1 - 2016/4/28

N2 - Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7% in the dexamethasone and 15.6 ± 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9% for dexamethasone and 80.8 ± 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7%; prednisone, 90.5 ± 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4%; prednisone, 82.6 ± 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457).

AB - Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7% in the dexamethasone and 15.6 ± 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9% for dexamethasone and 80.8 ± 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7%; prednisone, 90.5 ± 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4%; prednisone, 82.6 ± 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457).

KW - Journal Article

U2 - 10.1182/blood-2015-09-670729

DO - 10.1182/blood-2015-09-670729

M3 - Article

VL - 127

SP - 2101

EP - 2112

JO - Blood

JF - Blood

SN - 0006-4971

IS - 17

ER -