Abstract
Extramedullary relapse of acute myeloid leukemia (AML) is not a rare event, and the FMS-like tyrosine kinase 3 (FLT3) mutation is a well-known risk factor. Gilteritinib is approved for relapsed/refractory FLT3+ AML, but its efficacy in extramedullary relapse is still undefined. Here, we present the case of a 69-year-old woman with therapy-related nucleophosmin-1 and FLT3-internal tandem duplication (FLT3-ITD) positive AML treated with induction and consolidation with CPX-351 (liposomal daunorubicin plus cytarabine) followed by off-label azacitidine maintenance who obtained a complete remission (CR) with persistent measurable residual disease. After 19 months of CR, she experienced an isolated breast relapse of FLT3-ITD+ AML. She was started on single-agent gilteritinib, resulting in a rapid and persistent complete regression of the breast nodule. Targeted therapy with gilteritinib for relapsed/refractory FLT3-ITD+ AML can be effective in isolated extramedullary relapse.
References
1.
Pollyea
DA
, Bixby
D
, Perl
A
, Bhatt
VR
, Altman
JK
, Appelbaum
FR
, Acute myeloid leukemia, version 2.2021 featured updates to the NCCN guidelines
. J Natl Compr Cancer Netw
. 2021
;19
(1
):16
–27
.2.
Welch
JS
, Ley
TJ
, Link
DC
, Miller
CA
, Larson
DE
, Koboldt
DC
, The origin and evolution of mutations in acute myeloid leukemia
. Cell
. 2013
;150
(2
):264
–78
.3.
Papaemmanuil
E
, Gerstung
M
, Bullinger
L
, Gaidzik
VI
, Paschka
P
, Roberts
ND
, Genomic classification and prognosis in acute myeloid leukemia
. N Engl J Med
. 2016
;374
(23
):2209
–21
.4.
Perl
AE
, Martinelli
G
, Cortes
JE
, Neubauer
A
, Berman
E
, Paolini
S
, Gilteritinib or chemotherapy for relapsed or refractory FLT3 -mutated AML
. N Engl J Med
. 2019
;381
(18
):1728
–40
.5.
Patel
JP
, Gönen
M
, Figueroa
ME
, Fernandez
H
, Sun
Z
, Racevskis
J
, Prognostic relevance of integrated genetic profiling in acute myeloid leukemia
. N Engl J Med
. 2013
;366
(12
):1079
–89
.6.
Cerrano
M
, Duchmann
M
, Kim
R
, Vasseur
L
, Hirsch
P
, Thomas
X
, Clonal dominance is an adverse prognostic factor in acute myeloid leukemia treated with intensive chemotherapy
. Leukemia
. 2021
;35
(3
):712
–23
.7.
Döhner
H
, Estey
E
, Grimwade
D
, Amadori
S
, Appelbaum
FR
, Büchner
T
, Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
. Blood
. 2017
;129
(4
):424
–47
.8.
Solh
M
, Solomon
S
, Morris
L
, Holland
K
, Bashey
A
. Extramedullary acute myelogenous leukemia
. Blood Rev
. 2016
;30
(5
):333
–9
. .9.
Yilmaz
AF
, Saydam
G
, Sahin
F
, Baran
Y
. Granulocytic sarcoma: a systematic review
. Am J Blood Res
. 2013
;3
(4
):265
–70
.10.
Bakst
RL
, Tallman
MS
, Douer
D
, Yahalom
J
. How I treat extramedullary acute myeloid leukemia
. Blood
. 2011
;118
(14
):3785
–93
. .11.
Bourlon
C
, Lipton
JH
, Deotare
U
, Gupta
V
, Kim
DD
, Kuruvilla
J
, Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1
. Eur J Haematol
. 2017
;99
(3
):234
–9
.12.
Kida
M
, Kuroda
Y
, Kido
M
, Chishaki
R
, Kuraoka
K
, Ito
T
. Successful treatment with gilteritinib for isolated extramedullary relapse of acute myeloid leukemia with FLT3-ITD mutation after allogeneic stem cell transplantation
. Int J Hematol
. 2020
;112
(2
):243
–8
. .13.
Perrone
S
, Ortu La Barbera
E
, Viola
F
, Cipollone
E
, Scerpa
MC
, Siniscalchi
R
, A relapsing meningeal acute myeloid leukaemia FLT3-ITD+ responding to gilteritinib
. Chemotherapy
. 2021
;66
(4
):134
–8
.14.
Kumode
T
, Rai
S
, Tanaka
H
, Espinoza
JL
, Kakutani
H
, Watatani
Y
, Targeted therapy for medullary and extramedullary relapse of FLT3-ITD acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation
. Leuk Res Rep
. 2020
;14
:100219
.15.
Kim
RS
, Yaghy
A
, Wilde
LR
, Shields
CL
. An iridociliochoroidal myeloid sarcoma associated with relapsed acute myeloid leukemia with FLT3-ITD mutation, treated with gilteritinib, an FLT3 inhibitor
. JAMA Ophthalmol
. 2020 Apr 1
;138
(4
):418
–9
. .16.
McMahon
CM
, Canaani
J
, Rea
B
, Sargent
RL
, Qualtieri
JN
, Watt
CD
, Gilteritinib induces differentiation in relapsed and refractory FLT3-mutated acute myeloid leukemia
. Blood Adv
. 2019
;3
(10
):1581
–5
.17.
Krönke
J
, Bullinger
L
, Teleanu
V
, Tschürtz
F
, Gaidzik
VI
, Kühn
MWM
, Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia
. Blood
. 2013 Jul 4
;122
(1
):100
–8
.18.
Burns
A
. Observations of surgical anatomy, head and neck
. Edinburgh
: Thomas Royce
; 1811
. p. 364
–6
.19.
20.
Cui
Y
, Zhou
JL
, Wu
JH
, Zhang
JZ
. Synchronous granulocytic sarcoma of the breast and spine: a case report and review of the literature
. Chin Med J
. 2008
;121
(18
):1854
–6
. .21.
Dock
G.
Chloroma and its relation to leukemia
. Am J Med Sci
. 1893
;106
(2
):153
–7
.22.
Gomaa
W
, Ghanim
A
, Emam
E
, Bayoumi
K
, Ghanim
A
. Primary myeloid sarcoma of the breast: a case report and review of literature
. J Microsc Ultrastruct
. 2018
;6
(4
):212
–4
.23.
Yui
J
, Mudireddy
M
, Patnaik
MM
, Gangat
N
, Al-Kali
A
, Elliott
M
, Myeloid sarcoma: the Mayo Clinic experience of ninety six case series
. Blood
. 2016 Dec 2
;128
(22
):2798
.24.
Sharma
A
, Das
AK
, Pal
S
, Bhattacharyya
S
. Fine-needle aspiration cytology of granulocytic sarcoma presenting as a breast lump: report of a rare case with a comprehensive literature search
. J Lab Physicians
. 2018
;10
:113
–5
. .25.
Jelić-Puškarić
B
, Ostojić-Kolonić
S
, Planinc-Peraica
A
, Obad-Kovačević
D
, Kardum-Skelin
I
, Jakšić
B
. Myeloid sarcoma involving the breast
. Coll Antropol
. 2010
;34
(2
):641
–4
.26.
Zhang
XH
, Zhang
R
, Li
Y
. Granulocytic sarcoma of abdomen in acute myeloid leukemia patient with inv(16) and t(6;17) abnormal chromosome: case report and review of literature
. Leuk Res
. 2010
;34
(7
):958
–61
. .27.
Ganzel
C
, Lee
JW
, Fernandez
HF
, Paietta
EM
, Luger
SM
, Lazarus
HM
, CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials
. Blood Adv
. 2021
;5
(22
):4560
–8
.28.
Heuser
M
, Ofran
Y
, Boissel
N
, Brunet Mauri
S
, Craddock
C
, Janssen
J
, Acute myeloid leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up
. Ann Oncol
. 2020
;31
(6
):697
–712
.29.
Cunningham
I
, Kohno
B
. 18FDG-PET/CT: 21st century approach to leukemic tumors in 124 cases
. Am J Hematol
. 2016
;91
(4
):379
–84
.30.
Grunwald
MR
, Levis
MJ
. FLT3 tyrosine kinase inhibition as a paradigm for targeted drug development in acute myeloid leukemia
. Semin Hematol
. 2015
;52
(3
):193
–9
. .31.
Urbino
I
, Secreto
C
, Olivi
M
, Apolito
V
, D’ardia
S
, Frairia
C
, Evolving therapeutic approaches for older patients with acute myeloid leukemia in 2021
. Cancers
. 2021
;13
(20
):5075
.© 2022 S. Karger AG, Basel
2022
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.
You do not currently have access to this content.
