Abstract
We analyzed 217 patients with KMT2A-rearranged acute myeloid leukemia (AML) in 2 large sequential randomized trials. Those randomized to FLAG-Ida (fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubucin) had markedly lower rates of relapse than other chemotherapy regimens. Molecular measurable residual disease assessment after cycle 2 was strongly prognostic for relapse and death. The trials were registered at the ISRCTN Registry as AML17 ISRCTN55675535 and AML19 ISRCTN78449203.
References
1.
Papaemmanuil
E
, Gerstung
M
, Bullinger
L
, et al. Genomic classification and prognosis in acute myeloid leukemia
. N Engl J Med
. 2016
;374
(23
):2209
-2221
.2.
Grimwade
D
, Hills
RK
, Moorman
AV
, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials
. Blood
. 2010
;116
(3
):354
-365
.3.
Meyer
C
, Larghero
P
, Almeida Lopes
B
, et al. The KMT2A recombinome of acute leukemias in 2023
. Leukemia
. 2023
;37
(5
):988
-1005
.4.
Bill
M
, Mrózek
K
, Kohlschmidt
J
, et al. Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/ KMT2A
. Proc Natl Acad Sci USA
. 2020
;117
(42
):26340
-26346
.5.
Krauter
J
, Wagner
K
, Schäfer
I
, et al. Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data–based meta-analysis of the German Acute Myeloid Leukemia Intergroup
. J Clin Oncol
. 2009
;27
(18
):3000
-3006
.6.
Chen
Y
, Kantarjian
H
, Pierce
S
, et al. Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation
. Leukemia
. 2013
;27
(4
):836
-842
.7.
Vetro
C
, Haferlach
T
, Meggendorfer
M
, et al. Cytogenetic and molecular genetic characterization of KMT2A-PTD positive acute myeloid leukemia in comparison to KMT2A-rearranged acute myeloid leukemia
. Cancer Genet
. 2020
;240
:15
-22
.8.
Döhner
H
, Wei
AH
, Appelbaum
FR
, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
. Blood
. 2022
;140
(12
):1345
-1377
.9.
Hernández-Sánchez
A
, González
T
, Sobas
M
, et al. Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications – a HARMONY study
. Leukemia
. 2024
;38
(9
):1929
-1937
.10.
Issa
GC
, Zarka
J
, Sasaki
K
, et al. Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements
. Blood Cancer J
. 2021
;11
(9
):162
.11.
Schoch
C
, Schnittger
S
, Klaus
M
, Kern
W
, Hiddemann
W
, Haferlach
T
. AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases
. Blood
. 2003
;102
(7
):2395
-2402
.12.
Issa
GC
, Aldoss
I
, Thirman
MJ
, et al. Menin inhibition with revumenib for KMT2A-rearranged relapsed or refractory acute leukemia (AUGMENT-101)
. J Clin Oncol
. 2025
;43
(1
):75
-84
.13.
Loo
S
, Potter
N
, Ivey
A
, et al. Pretransplant MRD detection of fusion transcripts is strongly prognostic in KMT2A-rearranged acute myeloid leukemia
. Blood
. 2024
;144
(24
):2554
-2557
.14.
Wang
L
, Chen
Y
, Zang
M
, et al. Molecular measurable residual disease before transplantation independently predicts survival and relapse risk in adult lysine methyltransferase 2a-rearranged acute myeloid leukemia
. Cancer
. 2025
;131
(2
):e35717
.15.
Scholl
C
, Schlenk
RF
, Eiwen
K
, et al. The prognostic value of MLL-AF9 detection in patients with t(9;11)(p22;q23)-positive acute myeloid leukemia
. Haematologica
. 2005
;90
(12
):1626
-1634
.16.
Mitterbauer
G
, Zimmer
C
, Pirc-Danoewinata
H
, et al. Monitoring of minimal residual disease in patients with MLL–AF6-positive acute myeloid leukaemia by reverse transcriptase polymerase chain reaction
. Br J Haematol
. 2000
;109
(3
):622
-628
.17.
Mitterbauer
G
, Zimmer
C
, Fonatsch
C
, et al. Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR
. Leukemia
. 1999
;13
(10
):1519
-1524
.18.
Matsuo
H
, Iijima-Yamashita
Y
, Yamada
M
, et al. Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia
. Pediatr Int
. 2018
;60
(1
):41
-46
.19.
Juul-Dam
KL
, Ommen
HB
, Nyvold
CG
, et al. Measurable residual disease assessment by qPCR in peripheral blood is an informative tool for disease surveillance in childhood acute myeloid leukaemia
. Br J Haematol
. 2020
;190
(2
):198
-208
.20.
Huang
S
, Yang
H
, Li
Y
, et al. Prognostic significance of mixed-lineage leukemia (MLL) gene detected by real-time fluorescence quantitative PCR assay in acute myeloid leukemia
. Med Sci Monit
. 2016
;22
:3009
-3017
.21.
Burnett
AK
, Hills
RK
, Nielsen
OJ
, et al. A comparison of FLAG-Ida and daunorubicin combined with clofarabine in high-risk acute myeloid leukaemia: data from the UK NCRI AML17 trial
. Leukemia
. 2018
;32
(12
):2693
-2697
.22.
Burnett
A
, Cavenagh
J
, Russell
N
, et al. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 trial
. Haematologica
. 2016
;101
(6
):724
-731
.23.
Burnett
AK
, Russell
NH
, Hills
RK
, et al. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients
. Blood
. 2015
;125
(25
):3878
-3885
.24.
Burnett
AK
, Russell
NH
, Hills
RK
, et al. Defining the optimal total number of chemotherapy courses in younger patients with acute myeloid leukemia: a comparison of three versus four courses
. J Clin Oncol
. 2021
;39
(8
):890
-901
.25.
Russell
NH
, Wilhelm-Benartzi
C
, Othman
J
, et al. Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed AML and overall survival in patients with NPM1 and FLT3 mutations
. J Clin Oncol
. 2024
;42
(10
):1158
-1168
.26.
Othman
J
, Wilhelm-Benartzi
C
, Dillon
R
, et al. A randomized comparison of CPX-351 and FLAG-Ida in adverse karyotype AML and high-risk MDS: the UK NCRI AML19 trial
. Blood Adv
. 2023
;7
(16
):4539
-4549
.27.
Potter
N
, Xavier
S
, Auken
P
, et al. Targeted RNA sequencing frequently identifies high-risk fusion genes in younger adults with otherwise intermediate-risk AML and isolated FLT3-ITD [abstract]
. HemaSphere
. 2024
;8
(S1
). Abstract P449.28.
Freeman
SD
, Hills
RK
, Virgo
P
, et al. Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in patients at standard risk without NPM1 mutations
. J Clin Oncol
. 2018
;36
(15
):1486
-1497
.29.
DiNardo
CD
, Jen
W-Y
, Takahashi
K
, et al. Long term results of venetoclax combined with FLAG-IDA induction and consolidation for newly diagnosed and relapsed or refractory acute myeloid leukemia
. Leukemia
. 2025
;39
(4
):854
-863
.© 2025 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
2025
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