Abstract
Introduction: The first-line therapy for patients with low-risk myelodysplastic syndromes (MDSs) commonly consists of erythropoietin stimulating agents (ESAs), with a response rate ranging from 34 to 62%. For nonresponder patients, outside clinical trials, blood transfusions are the most frequent therapeutic option, with detrimental effect on the quality of life and with risks of iron-overload. Since no studies have been yet conducted on this topic, we investigated the potential predictive role of bone marrow (BM) histological evaluation in patients treated with ESAs. Materials and Methods: We performed a morphological and immunohistochemical retrospective analysis of BM biopsies of 96 patients with low-risk MDSs subsequently treated with ESAs. Results: In our series, substantial morphological overlap was found between responder and nonresponder patients. On the contrary, patients with a percentage of CD34-positive blasts >3% or with p53 protein expression <1% responded with a significantly higher frequency to ESAs. Conclusions: Our study reinforces the role of BM biopsy as diagnostic tool in MDSs, being also able to supply information related to response to ESAs and to its loss over time.
References
1.
Gascon
P
, Krendyukov
A
, Mathieson
N
, Aapro
M
. Epoetin alfa for the treatment of myelodysplastic syndrome-related anemia: a review of clinical data, clinical guidelines, and treatment protocols
. Leuk Res
. 2019
;81
:35
–42
.2.
Jadersten
M
, Malcovati
L
, Dybedal
I
, Della Porta
MG
, Invernizzi
R
, Montgomery
SM
, et al Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome
. J Clin Oncol
. 2008
;26
:3607
–13
.3.
Park
S
, Grabar
S
, Kelaidi
C
, Beyne-Rauzy
O
, Picard
F
, Bardet
V
, et al Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience
. Blood
. 2008
;111
(2
):574
–82
. .4.
Greenberg
PL
, Sun
Z
, Miller
KB
, Bennett
JM
, Tallman
MS
, Dewald
G
, et al Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996)
. Blood
. 2009
;114
(12
):2393
–400
. .5.
Cheson
BD
, Bennett
JM
, Kantarjian
H
, Pinto
A
, Schiffer
CA
, Nimer
SD
, et al Report of an international working group to standardize response criteria for myelodysplastic syndromes
. Blood
. 2000
;96
(12
):3671
–4
.6.
Cheson
BD
, Greenberg
PL
, Bennett
JM
, Lowenberg
B
, Wijermans
PW
, Nimer
SD
, et al Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia
. Blood
. 2006
;108
(2
):419
–25
. .7.
Zeidan
AM
, Giri
S
, DeVeaux
M
, Ballas
SK
, Duong
VH
. Systematic review and meta-analysis of the effect of iron chelation therapy on overall survival and disease progression in patients with lower-risk myelodysplastic syndromes
. Ann Hematol
. 2019
;98
(2
):339
–50
. .8.
Park
S
, Kelaidi
C
, Meunier
M
, Casadevall
N
, Gerds
AT
, Platzbecker
U
. The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion
. Ann Hematol
. 2020
;99
(1
):7
–19
. .9.
Hellstrom-Lindberg
E
, Gulbrandsen
N
, Lindberg
G
, Ahlgren
T
, Dahl
IM
, Dybedal
I
, et al A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life
. Br J Haematol
. 2003
;120
:1037
–46
.10.
Molteni
A
, Ravano
E
, Riva
M
, Nichelatti
M
, Bandiera
L
, Crucitti
L
, et al Prognostic impact of immunohistochemical p53 expression in bone marrow biopsy in higher risk MDS: a Pilot Study
. Mediterr J Hematol Infect Dis
. 2019
;11
(1
):e2019015
. .11.
Barosi
G
, Bordessoule
D
, Briere
J
, Cervantes
F
, Demory
JL
, Dupriez
B
, et al Response criteria for myelofibrosis with myeloid metaplasia: results of an initiative of the European Myelofibrosis Network (EUMNET)
. Blood
. 2005
;106
(8
):2849
–53
. .12.
Saft
L
, Karimi
M
, Ghaderi
M
, Matolcsy
A
, Mufti
GJ
, Kulasekararaj
A
, et al p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q)
. Haematologica
. 2014
;99
:1041
–9
.13.
Fenaux
P
, Haase
D
, Sanz
GF
, Santini
V
, Buske
C
. Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up
. Ann Oncol
. 2014
;25
(Suppl 3
):iii57
–69
. .14.
Krantz
SB
. Erythropoietin
. Blood
. 1991
;77
(3
):419
–34
. .15.
Shinjo
K
, Takeshita
A
, Higuchi
M
, Ohnishi
K
, Ohno
R
. Erythropoietin receptor expression on human bone marrow erythroid precursor cells by a newly-devised quantitative flow-cytometric assay
. Br J Haematol
. 1997
;96
(3
):551
–8
. .16.
Smock
KJ
, Perkins
SL
, Bahler
DW
. Quantitation of plasma cells in bone marrow aspirates by flow cytometric analysis compared with morphologic assessment
. Arch Pathol Lab Med
. 2007
;131
(6
):951
–5
. .17.
Rawstron
AC
, Orfao
A
, Beksac
M
, Bezdickova
L
, Brooimans
RA
, Bumbea
H
, et al Report of the European myeloma network on multiparametric flow cytometry in multiple myeloma and related disorders
. Haematologica
. 2008
;93
(3
):431
–8
. .18.
Barlow
JL
, Drynan
LF
, Trim
NL
, Erber
WN
, Warren
AJ
, McKenzie
AN
. New insights into 5q- syndrome as a ribosomopathy
. Cell Cycle
. 2010
;9
(21
):4286
–93
. .19.
Caceres
G
, McGraw
K
, Yip
BH
, Pellagatti
A
, Johnson
J
, Zhang
L
, et al TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients
. Proc Natl Acad Sci U S A
. 2013
;110
:16127
–32
.20.
Dutt
S
, Narla
A
, Lin
K
, Mullally
A
, Abayasekara
N
, Megerdichian
C
, et al Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells
. Blood
. 2011
;117
(9
):2567
–76
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2021
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