Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial

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Optimization of chemotherapy for younger patients with acute myeloid leukemia : results of the medical research council AML15 trial. / Burnett, Alan K; Russell, Nigel H; Hills, Robert K; Hunter, Ann E; Kjeldsen, Lars; Yin, John; Gibson, Brenda E S; Wheatley, Keith; Milligan, Donald.

In: Journal of Clinical Oncology , Vol. 31, No. 27, 20.09.2013, p. 3360-8.

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Burnett, Alan K ; Russell, Nigel H ; Hills, Robert K ; Hunter, Ann E ; Kjeldsen, Lars ; Yin, John ; Gibson, Brenda E S ; Wheatley, Keith ; Milligan, Donald. / Optimization of chemotherapy for younger patients with acute myeloid leukemia : results of the medical research council AML15 trial. In: Journal of Clinical Oncology . 2013 ; Vol. 31, No. 27. pp. 3360-8.

Bibtex

@article{9ba2a8c20f32424a8ef52a8afa3f87fd,
title = "Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial",
abstract = "PURPOSE: Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation.PATIENTS AND METHODS: Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m(2) or 1.5 g/m(2) (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227).RESULTS: Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m(2)), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation.CONCLUSION: FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m(2) is equivalent to a 3 g/m(2) dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.",
keywords = "Adolescent, Adult, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols, Child, Child, Preschool, Consolidation Chemotherapy, Cytarabine, Female, Granulocyte Colony-Stimulating Factor, Humans, Idarubicin, Infant, Leukemia, Myeloid, Acute, Male, Middle Aged, Treatment Outcome, Vidarabine, Young Adult",
author = "Burnett, {Alan K} and Russell, {Nigel H} and Hills, {Robert K} and Hunter, {Ann E} and Lars Kjeldsen and John Yin and Gibson, {Brenda E S} and Keith Wheatley and Donald Milligan",
year = "2013",
month = sep,
day = "20",
doi = "10.1200/JCO.2012.47.4874",
language = "English",
volume = "31",
pages = "3360--8",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "27",

}

RIS

TY - JOUR

T1 - Optimization of chemotherapy for younger patients with acute myeloid leukemia

T2 - results of the medical research council AML15 trial

AU - Burnett, Alan K

AU - Russell, Nigel H

AU - Hills, Robert K

AU - Hunter, Ann E

AU - Kjeldsen, Lars

AU - Yin, John

AU - Gibson, Brenda E S

AU - Wheatley, Keith

AU - Milligan, Donald

PY - 2013/9/20

Y1 - 2013/9/20

N2 - PURPOSE: Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation.PATIENTS AND METHODS: Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m(2) or 1.5 g/m(2) (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227).RESULTS: Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m(2)), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation.CONCLUSION: FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m(2) is equivalent to a 3 g/m(2) dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.

AB - PURPOSE: Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation.PATIENTS AND METHODS: Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m(2) or 1.5 g/m(2) (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227).RESULTS: Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m(2)), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation.CONCLUSION: FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m(2) is equivalent to a 3 g/m(2) dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.

KW - Adolescent

KW - Adult

KW - Age Factors

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Child

KW - Child, Preschool

KW - Consolidation Chemotherapy

KW - Cytarabine

KW - Female

KW - Granulocyte Colony-Stimulating Factor

KW - Humans

KW - Idarubicin

KW - Infant

KW - Leukemia, Myeloid, Acute

KW - Male

KW - Middle Aged

KW - Treatment Outcome

KW - Vidarabine

KW - Young Adult

U2 - 10.1200/JCO.2012.47.4874

DO - 10.1200/JCO.2012.47.4874

M3 - Article

C2 - 23940227

VL - 31

SP - 3360

EP - 3368

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 27

ER -