Optimization of Chemotherapy for Younger Patients With Acute Myeloid Leukemia: Results of the Medical Research Council AML15 Trial

被引：321

作者：

Burnett, Alan K. ^{[1
]}

Russell, Nigel H. ^{[2
]}

Hills, Robert K. ^{[1
]}

Hunter, Ann E. ^{[3
]}

Kjeldsen, Lars ^{[8
]}

Yin, John ^{[4
]}

Gibson, Brenda E. S. ^{[5
]}

Wheatley, Keith ^{[6
]}

Milligan, Donald ^{[7
]}

Kjeldsen, Lars ^{[8
]}

机构：

[1] Cardiff Univ, Sch Med, Cardiff CF14 4XN, S Glam, Wales

[2] Nottingham Univ Hosp Natl Hlth Serv Trust, Nottingham, England

[3] Leicester Royal Infirm, Leicester, Leics, England

[4] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England

[5] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland

[6] Univ Birmingham, Canc Res UK Clin Trials Unit, Birmingham B15 2TT, W Midlands, England

[7] Birmingham Heartlands Hosp, Birmingham B9 5ST, W Midlands, England

[8] Rigshosp, DK-2100 Copenhagen, Denmark

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2013年 / 31卷 / 27期

基金：

英国医学研究理事会;

关键词：

HIGH-DOSE DAUNORUBICIN; MYELODYSPLASTIC SYNDROMES; INDUCTION CHEMOTHERAPY; GEMTUZUMAB OZOGAMICIN; OLDER PATIENTS; FLAG-IDA; G-CSF; FLUDARABINE; CYTARABINE; SURVIVAL;

D O I：

10.1200/JCO.2012.47.4874

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2013 by American Society of Clinical Oncology

引用

页码：3360 / +

页数：15

共 50 条

[41] Feasibility of outpatient consolidation chemotherapy in older versus younger patients with acute myeloid leukemia
Saini, Lalit
Minden, Mark D.
Schuh, Andre C.
Yee, Karen W. L.
Schimmer, Aaron D.
Gupta, Vikas
Atenafu, Eshetu G.
Murray, Cindy
Nixon, Shannon
Brandwein, Joseph M.
AMERICAN JOURNAL OF HEMATOLOGY, 2012, 87 (03) : 323 - 326
[42] RESULTS OF MEDICAL-RESEARCH-COUNCIL TRIAL UKALL IX IN ACUTE LYMPHOBLASTIC-LEUKEMIA IN ADULTS - REPORT FROM THE MEDICAL-RESEARCH-COUNCIL WORKING PARTY ON ADULT LEUKEMIA
DURRANT, IJ
RICHARDS, SM
BRITISH JOURNAL OF HAEMATOLOGY, 1993, 85 (01) : 84 - 92
[43] Quality of life in patients with acute myeloid leukemia (AML):: Early results from the randomized AMLCG 1999 trial
Schumacher, A
Wewers, D
Heinecke, A
Berdel, WE
Hiddemann, W
Wörmann, B
Büchner, T
PSYCHO-ONCOLOGY, 2003, 12 (04) : S117 - S117
[44] A NEW PROGNOSTIC MODEL FOR PATIENTS WITH SECONDARY ACUTE MYELOID LEUKEMIA: RESULTS OF THE DSIL AML96 TRIAL
Schaich, M.
Aulitzky, W. E.
Bodenstein, H.
Bornhaeuser, M.
Illmer, T.
Schaekel, U.
Schmitz, N.
Soucek, S.
Thiede, C.
Wandt, H.
Ehninger, G.
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2008, 93 : 15 - 15
[45] Elderly patients with acute myeloid leukemia are not all the same: Results of the prospective DSIL AML96 trial
Schaich, Markus Andreas
Aulitzky, Walter E.
Bodenstein, Heinrich
Borrihaeuser, Martin
Illmer, Thomas
Schaekel, Ulrike
Schmitz, Nrbert
Schuler, Ulrich S.
Soucek, Silke
Thiede, Christian
Wandt, Hannes
Ehninger, Gerhard
BLOOD, 2007, 110 (11) : 545A - 545A
[46] Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia
Mueller-Tidow, C.
Tschanter, P.
Roellig, C.
Thiede, C.
Koschmieder, A.
Stelljes, M.
Koschmieder, S.
Dugas, M.
Gerss, J.
Butterfass-Bahloul, T.
Wagner, R.
Eveslage, M.
Thiem, U.
Krause, S. W.
Kaiser, U.
Kunzmann, V.
Steffen, B.
Noppeney, R.
Herr, W.
Baldus, C. D.
Schmitz, N.
Goetze, K.
Reichle, A.
Kaufmann, M.
Neubauer, A.
Schaefer-Eckart, K.
Haenel, M.
Peceny, R.
Frickhofen, N.
Kiehl, M.
Giagounidis, A.
Goerner, M.
Repp, R.
Link, H.
Kiani, A.
Naumann, R.
Bruemmendorf, Th
Serve, H.
Ehninger, G.
Berdel, W. E.
Krug, U.
LEUKEMIA, 2016, 30 (03) : 555 - 561
[47] Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia
C Müller-Tidow
P Tschanter
C Röllig
C Thiede
A Koschmieder
M Stelljes
S Koschmieder
M Dugas
J Gerss
T Butterfaß-Bahloul
R Wagner
M Eveslage
U Thiem
S W Krause
U Kaiser
V Kunzmann
B Steffen
R Noppeney
W Herr
C D Baldus
N Schmitz
K Götze
A Reichle
M Kaufmann
A Neubauer
K Schäfer-Eckart
M Hänel
R Peceny
N Frickhofen
M Kiehl
A Giagounidis
M Görner
R Repp
H Link
A Kiani
R Naumann
T H Brümmendorf
H Serve
G Ehninger
W E Berdel
U Krug
Leukemia, 2016, 30 : 555 - 561
[48] Decision criteria for the futility of intensive chemotherapy in older patients with acute myeloid leukemia (AML)
Dombrel, Herve
Malfuson, Jean-Valere
Etienne, Anne
Turlure, Pascal
de Revel, Thierry
Thomas, Xavier
Contentin, Nathalie
Terre, Christine
Michallet, Mauricette
Castaigne, Sylvie
Bordessoule, Dominique
Vey, Norbert
Gardin, Claude
BLOOD, 2007, 110 (11) : 841A - 842A
[49] Tailored non aggressive chemotherapy for elderly frail patients with acute myeloid leukemia (AML)
Chierichini, A.
Anaclerico, B.
Cedrone, M.
Fenu, S.
Bongarzoni, V
Bartolini, M.
Ronci, B.
Anticoli Borza, P.
Iacovino, M.
Annino, L.
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2007, 92 : 68 - 68
[50] Severity of and contributors to distress in patients with acute myeloid leukemia (AML) receiving induction chemotherapy
LeBlanc, Thomas William
Wolf, Steven Paul
Davis, Debra M.
Samsa, Greg
Locke, Susan C.
El-Jawahri, Areej
Tulsky, James A.
Abernethy, Amy P.
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (29)

← 1 2 3 4 5 →