Abstract
Introduction: The standard induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) is 7 days cytarabine and 3 days daunorubicin. However, older and frail patients cannot be treated intensively. Before hypomethylating agents (HMA) plus venetoclax (VEN) was established we formulated a more tolerable induction therapy for these patients using continuous infusions of reduced doses of cytarabine (A) and idarubicin (IDA) in combination with ATRA (A), the (A)-AIDA regimen and trying to reach noteworthy and relevant remission rates with acceptable toxicities in this special population. Methods: Between 1998 and 2015 older/frail patients with newly diagnosed or relapsed AML received (A)-AIDA. Treatment consisted of cytarabine 100 mg/m2/d d1–5 and IDA 5 mg/m2/d d1–5 as continuous infusion. Since 2003 ATRA (45 mg/m2/d d4–6, 15 mg/m2/d d7–28) was added in some patients. Results: 154 patients received (A)-AIDA, median age was 71 years. In 40% the AML was secondary, 15.6% had relapsed AML. The complete remission rate was 41%, 7% reached a partial remission, the median overall survival was 7 months. No significant differences of remission rates regarding various known risk factors for outcome with (A)-AIDA were detected. Conlusion: Recent studies established HMA/VEN as first-line treatment for older/frail AML patients. Because (A)-AIDA is equally effective in patients with secondary or relapsed AML or ECOG >1, this regimen is an interesting treatment option for patients uneligible to HMA/VEN regimens.
Journal Section:
Research Article
References
1.
Oran
B
, Weisdorf
DJ
. Survival for older patients with acute myeloid leukemia: a population- based study
. Haematologica
. 2012
;97
(12
):1916
–24
. 2.
DiNardo
CD
, Jonas
BA
, Pullarkat
V
, Thirman
MJ
, Garcia
JS
, Wei
AH
, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia
. N Engl J Med
. 2020
;383
(7
):617
–29
. 3.
Döhner
H
, Weisdorf
DJ
, Bloomfield
CD
. Acute myeloid leukemia
. N Engl J Med
. 2015
;373
(12
):1136
–52
. 4.
Schlenk
RF
, Fröhling
S
, Hartmann
F
, Fischer
JT
, Glasmacher
A
, del Valle
F
, et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia
. Leukemia
. 2004
;18
(11
):1798
–803
. 5.
Löwenberg
B
, Ossenkoppele
GJ
, van Putten
W
, Schouten
HC
, Graux
C
, Ferrant
A
, et al. High-dose daunorubicin in older patients with acute myeloid leukemia
. N Engl J Med
. 2009
;361
(13
):1235
–48
. 6.
Wiernik
PH
, Banks
PL
, Case
DJ
, Arlin
ZA
, Periman
PO
, Todd
MB
, et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia
. Blood
. 1992
;79
(2
):313
–9
. 7.
Robert
J
, Rigal-Huguet
F
, Harousseau
JL
, Pris
J
, Huet
S
, Reiffers
J
, et al. Pharmacokinetics of idarubicin after daily intravenous administration in leukemic patients
. Leuk Res
. 1987
;11
(11
):961
–4
. 8.
Leoni
F
, Ciolli
S
, Giuliani
G
, Pascarella
A
, Caporale
R
, Salti
F
, et al. Attenuated-dose idarubicin in acute myeloid leukaemia of the elderly: pharmacokinetic study and clinical results
. Br J Haematol
. 1995
;90
(1
):169
–74
. 9.
Schlenk
RF
, Döhner
K
, Kneba
M
, Götze
K
, Hartmann
F
, Del Valle
F
, et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B
. Haematologica
. 2009
;94
(1
):54
–60
. 10.
von Lilienfeld-Toal
M
, Hahn-Ast
C
, Kirchner
H
, Flieger
D
, Dölken
G
, Glasmacher
A
. A randomized comparison of immediate versus delayed application of G-CSF in induction therapy for patients with acute myeloid leukemia unfit for intensive chemotherapy
. Haematologica
. 2007
;92
(12
):1719
–20
. 11.
Cheson
BD
, Bennett
JM
, Kopecky
KJ
, Büchner
T
, Willman
CL
, Estey
EH
, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia
. J Clin Oncol
. 2003
;21
(24
):4642
–9
. 12.
Döhner
H
, Estey
E
, Grimwade
D
, Amadori
S
, Appelbaum
FR
, Büchner
T
, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
. Blood
. 2017
;129
(4
):424
–47
. 13.
Glasmacher
A
, Prentice
AG
. Evidence-based review of antifungal prophylaxis in neutropenic patients with haematological malignancies
. J Antimicrob Chemother
. 2005
;56
(Suppl 1
):i23
–32
. 14.
Burnett
AK
, Milligan
D
, Prentice
AG
, Goldstone
AH
, McMullin
MF
, Hills
RK
, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment
. Cancer
. 2007
;109
(6
):1114
–24
. 15.
Kantarjian
HM
, Thomas
XG
, Dmoszynska
A
, Wierzbowska
A
, Mazur
G
, Mayer
J
, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia
. J Clin Oncol
. 2012
;30
(21
):2670
–7
. 16.
Dombret
H
, Seymour
JF
, Butrym
A
, Wierzbowska
A
, Selleslag
D
, Jang
JH
, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with 30% blasts
. Blood
. 2015
;126
(3
):291
–9
. 17.
DiNardo
CD
, Maiti
A
, Rausch
CR
, Pemmaraju
N
, Naqvi
K
, Daver
NG
, et al. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial
. Lancet Haematol
. 2020
;7
(10
):e724
–36
. 18.
Montesinos
P
, Recher
C
, Vives
S
, Zarzycka
E
, Wang
J
, Bertani
G
, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia
. N Engl J Med
. 2022
;386
(16
):1519
–31
. 19.
Bewersdorf
JP
, Zeidan
AM
. Hyperleukocytosis and leukostasis in acute myeloid leukemia: can a better understanding of the underlying molecular pathophysiology lead to novel treatments
. Cells
. 2020
;9
(10
):2310
. 20.
Appelbaum
FR
, Gundacker
H
, Head
DR
, Slovak
ML
, Willman
CL
, Godwin
JE
, et al. Age and acute myeloid leukemia
. Blood
. 2006
;107
(9
):3481
–5
. 21.
Kantarjian
H
, Ravandi
F
, O’Brien
S
, Cortes
J
, Faderl
S
, Garcia-Manero
G
, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia
. Blood
. 2010
;116
(22
):4422
–9
. 22.
Granfeldt Østgård
LS
, Medeiros
BC
, Sengeløv
H
, Nørgaard
M
, Andersen
MK
, Dufva
IH
, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study
. J Clin Oncol
. 2015
;33
(31
):3641
–9
. 23.
Lalayanni
C
, Gavriilaki
E
, Athanasiadou
A
, Iskas
M
, Papathanasiou
M
, Marvaki
A
, et al. Secondary acute myeloid leukemia (sAML): similarly dismal outcomes of AML after an antecedent hematologic disorder and therapy related AML
. Clin Lymphoma Myeloma Leuk
. 2022
;22
(4
):e233
–40
. 24.
Kurosawa
S
, Yamaguchi
T
, Miyawaki
S
, Uchida
N
, Sakura
T
, Kanamori
H
, et al. Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse
. Haematologica
. 2010
;95
(11
):1857
–64
. 25.
Döhner
H
, Wei
AH
, Appelbaum
FR
, Craddock
C
, DiNardo
CD
, Dombret
H
, 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
–77
. 26.
Abbas
S
, Lugthart
S
, Kavelaars
FG
, Schelen
A
, Koenders
JE
, Zeilemaker
A
, et al. Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value
. Blood
. 2010
;116
(12
):2122
–6
. © 2025 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2025
You do not currently have access to this content.
