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135]
Review Article
Management of myelodysplastic syndromes: Expert
consensus opinion from the Saudi MDS Working Group
Ahmed Alaskar1,2, Abdul Kareem Al Momen3, Ahmad AlSaeed1,2, Ahmed Al Sagheir4, Amr Hanbali5,
Ayman AlHejazi1,2, Hani AlHashmi4, Khalid AlAnazi4, Mohsen Al Zahrani1,2, Saud Abu Harbesh5,
Zayed AlZahrani1,2
1
King Abdullah International Medical Research Center, 2King Saud Bin Abdulaziz University for Health Sciences, 3King Khalid
University Hospital, King Saud University, 5Security Forces Hospital, Riyadh, 4King Fahad Specialist Hospital, Dammam,
Saudi Arabia
Address for correspondence: Dr. Ahmed Alaskar, Division of Adult Hematology and SCT, King Abdullah International Medical Research Center,
Ministry of National Guard Health Affairs, POB 22490, Riyadh 11426, Saudi Arabia. Email:askaras@ngha.med.sa
ABSTRACT
Myelodysplastic syndromes (MDSs) constitute a heterogeneous group of clonal hematopoietic disorders. A panel of Saudi
hematologists representing the Saudi MDS Working Group convened with two international experts to develop the guidelines
for MDS diagnosis and treatment. The recommendations were formulated on the basis of a list of real cases and therapyrelated
questions. The diagnostic procedures should help distinguish MDS from other causes of cytopenia and dysplasia and other clonal
stem cell disorders. Blood smear, bone marrow aspirate and biopsy, and cytogenetic testing are among the mandatory diagnostic
tests in MDS. Higher resolution genetic testing like mutational analysis and single nucleotide polymorphisms can be suggested
for the workup depending on the clinical condition and availability of these technologies. The Working Group stressed that the
heterogeneity of MDS strongly withstands a riskadapted treatment strategy based on the international prognostic scoring system
risk group of patients.
Key words: Consensus, diagnosis, guidelines, myelodysplastic syndromes, Saudi MDS Working Group, treatment
INTRODUCTION
However, unpublished data from previous experts

meetings raised the issue of increased refractory anemia
(RA) in the elderly patients in KSA who were eventually
given a late diagnosis of MDS. The idea of establishing
a national MDS registry in KSA is being entertained
by a group of hematologists, an endeavor that might
give us an idea about the incidence of MDS in KSA.
Myelodysplastic syndromes(MDSs) are a heterogeneous

group of myeloid neoplasms characterized by
peripheral blood cytopenias, dysplastic changes,
clonal chromosomal abnormalities and increased risk
of leukemic evolution.[1,2] Common risk factors for
developing MDS include advanced age, male gender,
family history of hematopoietic cancers, exposure to
solvents and agricultural chemicals, and prior chemoor
radiotherapy for previous solid cancer.[3,4] The incidence
rate of MDS in the USA and Western European
countries is approximately 5/100,000 people. [58]
Data on the incidence of MDS in Kingdom of Saudi
Arabia(KSA) is absent in the medical literature.
The pathophysiology of MDS is a multistep process

involving genetic mutations detectable by conventional
cytogenetic testing or smaller alterations detectable
by more advanced methods like sequencing or
single nucleotide polymorphism(SNP) array. [9,10]
MDSs range from indolent(socalled low risk)
conditions with long natural history to subtypes
analogous to acute myeloid leukemia(AML)(socalled
highrisk); this makes the clinical decision concerning
treatment modalities and timing of interventions
problematic.[11,12] Given the importance of fast and
accurate diagnosis of MDS, diagnostic criteria needed
to be periodically revised and updated in order to
incorporate modifications in classification criteria and
recent diagnostic methodologies.
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DOI:
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Vol. 5 Issue 4 October-December 2014
123
Journal of Applied Hematology
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Alaskar, etal.: Saudi MDS Working Group consensus opinion
METHODS
Table1: Blood tests in the diagnostic workup of

MDS
A panel of Saudi hematologists representing the newly

established Saudi MDS Working Group(SMW)
convened on two occasions in 2012/2013 to review
the diagnostic criteria and treatment option of MDS;
the meetings were characterized by discussions and
revision of many individual cases. During the second
meeting, the SMW met with two international
experts over2days in a scientific forum that covered
the key topics on diagnosis and recent advances in
MDS management. The ultimate objectives of the
SMW were to establish a consensus and publish the
guidelines for the management of MDS reflecting the
Saudi experience.
Tests
Hematology
WBC count with differential, RBC

count, hemoglobin, platelet count, MCV,
reticulocyte count, peripheral blood film
Basic chemistry panel, bilirubin, AST,
ALT, LDH, haptoglobin, iron, total iron
binding capacity, ferritin, folate, vitamin
B12, EPO level, thyroid function tests
Hepatitis serology(A, B and C), HIV,
parvovirus B19, CMV
PNH screen
Biochemistry
Virus
Others
WBC=White blood cell; RBC=Red blood cell; MCV=Mean corpuscular

volume; AST=Aspartate aminotransferase; ALT=Alanine aminotransferase;
EPO=Erythropoietin; HIV=Human Immunodeficiency Virus;
CMV=Cytomegalovirus; PNH=Paroxysmal nocturnal hemoglobinuria;
MDS=Myelodysplastic syndrome; LDH=Lactate dehydrogenase
Diagnostic Procedures
Repeated bone marrow examinations are sometimes

required to establish the diagnosis and to identify
patients with rapid disease progression. Patients might be
observed for 3-6months before repeating bone marrow
examination if cytogenetics was normal or nonrevealing
and if only unilineage dysplasia is present with no
increase in blasts or ring sideroblasts(represent<15%
of the erythroid precursors).
It is quite important that the diagnostic procedures

help distinguish MDS from other causes of
cytopenia and dysplasia and other clonal stem cell
disorders.[2] Complete information should be collected
on symptoms of anemia(palpitations, fatigue),
thrombocytopenia(bleeding, bruising, ecchymosis),
neutropenia(recurrent infections); chronicity of the
symptoms; prior chemotherapy, radiation exposure
or therapy, and occupational exposure(especially
to agricultural chemicals and benzene).[3,13] History
taking should gather information on concomitant
medications, smoking, alcohol intake, bleeding
tendency, autoimmune disorders, previous blood
transfusions, previous surgeries particularly bowel
resection, and infections. Collection of family
history should focus on conditions suggestive of
inherited bone marrow failure disorders, like Fanconi
anemia.[14,15]
Morphology(peripheral blood and bone marrow smears)
It is recommended to follow the World Health

Organization(WHO) 2008 classification of myeloid
neoplasms for evaluation of morphology and dysplasia
in blood and bone marrow.[2] Counting at least 300cells
in bone marrow smears is recommended. To qualify as
significant, the recommended requisite percentage of
bone marrow dysplastic cells are10% of the nucleated
cells in the lineage under consideration.
Myeloblasts are defined in terms of several nuclear
characteristics, including a high nuclear/cytoplasmic
ratio, easily visible nucleoli, with or without granules
or Auer rods, but no Golgi zone. Myeloblasts in
MDS should be classified as agranular(TypeI) or
granular(TypeII). Granular blasts must be distinguished
from promyelocytes, the latter having a clearly visible
Golgi zone.[16]
A thorough physical examination should be performed.

Among the things that should be examined are: Pallor,
petechiae, ecchymosis, mouth ulcers, glossitis, palmar
and plantar warts, dysmorphic features to rule out
constitutional bone marrow failure syndrome(facial
features, caf au lait spots, and nail dystrophy),
jaundice, features of hypothyroidism, lymphadenopathy,
features of portal hypertension, skeletal disorders, and
hepatosplenomegaly. Table1 summarizes the blood
tests of value in the diagnostic workup of suspected
MDSs.
Evaluation of bone marrow smears must include

iron staining to evaluate the presence and number
of ring sideroblasts. Ring sideroblasts are defined
as erythroblasts having a minimum of five siderotic
granules covering at least onethird of the nuclear
circumference.[16,17]
The next diagnostic approach to suspected MDS

includes morphologic studies of peripheral blood film
and bone marrow aspirate to evaluate abnormalities of
peripheral blood cells and hematopoietic precursors;
bone marrow biopsy to assess marrow cellularity, cell
morphology and fibrosis; cytogenetic testing to identify
clonal chromosomal abnormalities.
Blood test category
Note: An increase in white blood cell count with the

monocytosis might be seen in chronic myelomonocytic
leukemia1 or2 when an infection is encountered, and
this presentation might be mistaken for acute leukemia
124
transformation especially that the monocytes might

look bizarre on blood film. Treatment of the infection
will result in resolution of this exaggerated response.
Table2: New cytogenetic scoring system for

MDS
Subgroup
Single
Bone marrow biopsy
Very good
Good
del(11q),Y
Normal, del(5q),
del(12p), del(20q)
Intermediate del(7q), +8, i(17q),
+19, any other
independent clones
Poor
Inv(3)/t(3q)/del(3q)
A trephine biopsy should be performed in all cases

of suspected MDS whenever possible. Bone marrow
biopsy is needed to assess marrow cellularity and
fibrosis, abnormal localization of immature precursors,
blast compartment, and the presence of nonhematologic
cells, such as metastases. Immunohistochemistry with
antiCD34(allows the identification of CD34+blast
cellsparticularly useful when the aspirate is of
suboptimal quality because of bone marrow fibrosis
or hypocellularity), antiCD117 and antiCD61(stains
for abnormal megakar yocytes) should be done.
An important gene for prognosis in MDS, that is
recommended to be stained for in bone marrow
samples, is the p53 gene. Almost 85% of cases with
p53 mutation can be detected by immunohistochemical
stain. If>5% of the cells are p53 positive, then it is a
bad prognostic feature and entails shorter survival.[18]
Very poor
Complex
Any including
del(5q)
Any other
Including7/
del(7q)
>3
MDS=Myelodysplastic syndrome
clinical suspicion is high for MDS, fluorescence

insitu hybridization(FISH) should be done. FISH
improves the likelihood of identifying specific gene
rearrangements common in MDS. [27,28] FISH can
be performed on mitotic as well as on interphase
cells, which overcomes this limitation of metaphase
cytogenetics; thus, it can be quickly performed with
high sensitivity and specificity.[28] When the metaphase
cytogenetics is normal or in a situation when divisions
have failed to reveal the bands, FISH is recommended
to test for 5q, monosomy 7, trisomy 8, 20q, 12p, 4q,
and 17p.
The best way of estimating cellularity is 100minus

the patients age. The bone marrow in MDS is usually
hyperor normocellular, but in approximately 10% the
bone marrow is hypocellular(hypoplastic MDS).[19,20]
This group needs to be distinguished from aplastic
anemia morphologically. An increase in bone marrow
CD34+cells, presence of ring sideroblasts, and dysplasia
of either granulocytes or megakaryocytes have been
shown to be useful in distinguishing hypoplastic MDS
from cases of aplastic anemia.[21]
Molecular genetics
Highresolution SNPs can now be applied in karyotypic

testing with the advent in microarray technologies. SNP
does not depend upon the availability of dividing cells,
and consequently can be informative when routine
metaphase cytogenetics is not. Due to the higher
resolution of SNP array, smaller and previously cryptic
deletions and duplications can be detected. Amajor
advantage of SNP over metaphase cytogenetics is the
ability to detect copyneutral loss of heterozygosity,
which is caused by uniparental disomy.[29,30]
Cytogenetics
A cytogenetic analysis of bone marrow aspirate

should be performed in all patients with suspected
MDS. Cytogenetic analysis has a major role in
determining clonality in patients with suspected
MDS. Chromosomal abnormalities are observed
in up to 50% of patients with MDS; the most
frequent single cytogenetic abnormalities include
del (5q), monosomy 7 or del(7q), trisomy 8, and
del (20q).[2224] At least 20 metaphases should be
analyzed whenever possible and described according
to most recent International System for Human
Cytogenetic Nomenclature recommendations.[25] The
most recent system classifies cytogenetics according to
five prognostic subgroups[24][Table2], and this system
provided the foundation for the revised international
prognostic scoring system(IPSSR).[26]
In a recent study, the combination of metaphase

cytogenetics and SNP array karyotyping led to a higher
diagnostic yield of chromosomal defects compared
with that picked up with metaphase cytogenetics
alone, often through detection of novel lesions in
patients with normal or noninformative standard
cytogenetic results.[31] Consequently, the concurrent
use of SNP array and metaphase cytogenetics in the
initial karyotypic testing was shown to affect outcome
prediction and improve prognostic stratification of
MDS patients.
Acquired somatic mutations have been detected in
several genes, including genes that encode signal
transduction proteins(CBL, JAK2, KRAS, NRAS, and
In the case of repeated failure of standard Gbanding

(absent or poorquality metaphases) or the setting
of a normal metaphase cytogenetics when the
Cytogenetic abnormality
Double
125
PTPN11), transcription factors and cofactors (NPM1,

RUNX1, and p53) and epigenetic regulators (ASXL1,
DNMT3A, EZH2, IDH1, IDH2, and TET2).[18,3236]
Recently, mutations in genes encoding for spliceosome
components were identified in a high proportion of
MDS patients. These genes include SF3B1, SRSF2,
U2AF1, and ZRSR2, and SF3A1[37] [Figure1].
requirements, the WHO prognostic scoring system

was developed,[41] which classifies patients into five
risk groups[Table3].
Another scoring system specific for lower risk MDS
was established by MD Anderson prognostic scoring
system.[42] Lower risk MDS patients were divided
into three risk groups based on age, presence of poor
cytogenetics, hemoglobin, platelets, and percent of
blasts in the marrow[Table4].
MYELODYSPLASTIC SYNDROME
CLASSIFICATION AND SCORING SYSTEMS
The IPSS classification was developed in 1997 and

it combined clinical, cytogenetic and morphological
data in an attempt to improve on previous systems[43]
[Table5]. The IPSS system assigns scores based on
the initial cytogenetics, number of cytopenias and
percentage of blasts in bone marrow. The four IPSS
risk groups are low risk(score: 0), intermediate1 risk
(score: 0.5-1.0), intermediate2 risk(score: 1.5-2.0)
and high risk (score 2.5). MDS patients can be
stratified into lower risk(corresponding to IPSS low
and intermediate1) and higher risk(corresponding
to IPSS intermediate2 and high).[43] A new IPSSR
has recently been refined with multiple statistically
weighted clinical features used to generate a prognostic
categorization model[26][Table6]. Initial cytogenetics,
number of cytopenias, and the percentage of blasts in
bone marrow remained the basis of the revised system.
Changes included: Five rather than three cytogenetic
prognostic subgroups with new classifications of a
number of less common cytogenetic abnormalities;
splitting the low marrow blast percentage in those
with<2% blasts and those with 2-4% blasts; and depth
of cytopenias. This model defined five rather than the
four prognostic categories of the IPSS. Until recently,
the most commonly used system is the IPSS. However,
IPSS is likely to be replaced by a new IPSSR and the
incorporation of the new molecular markers recently
described.
Staging and prognostic scoring systems are

important to accurately diagnose, predict outcomes
and assist in selecting optimal treatment of MDS
patients.[38] Many scoring systems have been developed
and are continuously being refined to become more
convenient in evaluating optimal treatments.[11] The
FrenchAmericanBritish(FAB) classification is
the oldest scheme for the classification of MDS. It
divides MDS into five subtypes based on the bone
marrow morphology, including percentage of blasts
in the peripheral blood and bone marrow, presence or
absence of ring sideroblasts or increased circulating
monocytes.[39]
The WHO classification, which was revised in 2008,
is based on the FAB system but better delineates
each subtype by adding the criteria of the number of
lineages with dysplasia and incorporating a cytogenetic
abnormality.[40] In addition to defining the lowergrade
diseases, refractory cytopenia with unilineage dysplasia
and RA with ring sideroblasts(RARS) and the
addition of a new subtype, refractory cytopenia with
multilineage dysplasia, MDS with isolated del(5q)
was added. Two subtypes of RA with excess blasts were
also recognized. Based on the WHO classification,
cytogenetic abnormality pattern, and transfusion
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WHO
category
Karyotype^
Transfusion
requirements*
0
1
2
3
RA, RARS, 5q
RCMD
RAEB1
RAEB2
Good
Intermediate
Poor
None
Regular
Karyotypes: Good=Normal,Y, del(5q) only, del(20q) only;

Poor=Complex(3 abnormalities), or chromosome 7 abnormalities;
Intermediate=All others. *Transfusion dependency is defined as at least
one unit of red blood cells transfusion every 8weeks over a period of 4
months. WPSS=WHO prognostic scoring system; WHO=World Health
Organization; MDS=Myelodysplastic syndromes; RA=Refractory anemia;
RARS=Refractory anemia with ring sideroblasts; RCMD=Refractory
cytopenia with multilineage dysplasia; RAEB=Refractory anemia with
excess blasts
^
Figure1: Distribution of different molecular markers in myelodysplastic

syndromes
Score
126
safe treatments capable of modifying the natural history

of the disease are developed. It must be emphasized
that patients should understand that the safety of the
watchfulwaiting approach is dependent upon regular
monitoring. Patients should be regularly monitored for
the early recognition of worsening cytopenia(especially
transfusion dependence), increasing the number of
circulating or bone marrow blasts, and karyotypic
evolution.
Table4: MPSS for lower risk MDS

Adverse factor
Assigned score
Unfavorable cytogenetics*
Age>60years
Hemoglobin<10 g/dl
Platelets<50,000/uL
Platelets 50,000-200,000/uL
BM blasts>4%
1
2
1
2
1
1
Score
Median survival(months);
4year survival(%)
0
1
2
3
4
5
6
7
Hematopoietic growth factors
NR; 78
83; 82
51; 51
36; 40
22; 27
14; 9
16; 7
9; NA
Patients with IPSS low or intermediate1 risk, with

moderate to severe anemia(hemoglobin below 10g/dL),
serum erythropoietin level below 500 mU/mL, and/or
red cell transfusion requirement lower than two red
blood cell(RBC) units/month should be considered
for therapy with epoetin alfa or beta at an initial dose
ranging from 30,000 to 60,000IU/week.[45,46] Those
patients who do not respond to epoetin alone after
8weeks of treatment should be given granulocytecolony
stimulating factor(300 g/week in 2-3 divided doses)
in combination.
*Diploid and 5q only were favorable cytogenetics, all others were

considered as unfavorable cytogenetics. BM=Bone marrow; NR=Not
reached; NA=Not assessable; MPSS=MD Anderson prognostic scoring
system; MDS=Myelodysplastic syndromes
Table5: IPSS for MDS

Variable
0
0.5
Points
1
Marrow blasts(%)
<5
5-10
Karyotype^
Good Intermediate
Cytopenias*
0 or 1
2 or 3
1.5
Although the scientific evidence on darbepoetin alfa

is not comparable to that available for epoetin alfa or
beta in terms of number and size of studies, the results
suggest that the use of equipotent doses of this agent
may result in clinical effects similar to those obtained
with epoetin alfa or beta.
11-20 21-30
Poor
Score
IPSS risk group
Low
Intermediate 1
Intermediate 2
High
The available evidence does not allow any

recommendations to be made on the use of
thrombopoiesisstimulating agents (i.e. romiplostim,
eltrombopag), which should be restricted to clinical
trials.
0
0.5-1.0
1.5-2.0
2.5-3.5
Good=Normal, del(5q) only, del(20q) only,Y only; Poor=Very

complex(>2) abnormalities, chromosome 7 anomalies; Intermediate=Other
abnormalities; *Cytopenias=Hemoglobin<10 g/dL, neutrophil
count<1.5109/L, platelet count<100109/L. IPSS=International
prognostic scoring system; MDS=Myelodysplastic syndromes
^
Red blood cell transfusion and iron chelation therapy
The objective of RBC transfusion therapy is to improve

the qualityoflife and to avoid anemiarelated symptoms
and ischemic organ damage. No single hemoglobin
concentration can be recommended as being the
optimal level below which red cell support should be
given. The decision should be based on the patients
symptoms and comorbidities(especially cardiovascular
risk factors). As a general recommendation, all patients
with severe anemia(hemoglobin lower than 8g/dL) and
those with symptomatic milder anemia should receive
RBC transfusion.[47,48]
Therapy
The Working Group stressed that the heterogeneity

of MDS strongly withstands a riskadapted treatment
strategy based on the IPSS risk group of patients. The
treatment algorithms for MDS patients with low and
high IPSS scores are reported in Figures2 and 3.
Watchfulwaiting strategy
Adult patients with primary MDS, low IPSS risk, and

asymptomatic cytopenia do not need any treatment and
should be followed regularly. In addition, patients with
intermediate1 IPSS risk, asymptomatic cytopenia, no
blast excess, and no poorrisk cytogenetic abnormality
may be followed without specific treatment.[44] This
watchfulwaiting strategy might change in the future if
Iron chelation should be considered in

transfusiondependent patients with RA, RARS, or
MDS with isolated 5q deletion and a serum ferritin
level higher than 1000 ng/mL after approximately 25
units of red cells.[49] MDS patients who are potentially
candidates for allostem cell transplantation (SCT) can
127
Table6: IPSSR for MDS

Variable
0
Cytogenetics*
Bone marrow blasts(%)
Hemoglobin
Platelets
ANC
Very good
2
10
100
0.8
0.5
Points
1.5
50-<100
<0.8
Good
>2-<5
8-<10
<50
Intermediate
510
Poor
>10
Very poor
<8
Score
IPSSR risk group
Very low
Low
Intermediate
High
Very high
1.5
1.5-3
>3-4.5
>4.5-6
>6
*Refer to Table2 for cytogenetic risk groups. IPSSR=Revised international prognostic scoring system; MDS=Myelodysplastic syndromes; ANC=Absolute
neutrophil count
Low IPSS risk
Asymptomatic
Watchful-waiting
Symptomatic
EPO <500 mU/mL and/or

RBC units <2/month
rHuEPO +/- GCSF
MDS del(5q)
EPO 500 mU/mL

and/or RBC units
2/month
Lenalidomide
RBC transfusion
therapy
Age <60 years, BM blasts

<5%, normal cytogenetics,
transfusion dependency
(hypocellular BM)
EPO <500 mU/mL

and/or RBC units
<2/month
rHuEPO +/GCSF
ATGplus CSA
Figure2: Treatment algorithm for patients with lower risk myelodysplastic syndromes. rHuEPO, recombinant human erythropoietin; BM,
bone marrow; ATG, antithymocyte globulin; CSA, cyclosporine
be considered for appropriate iron chelation therapy

prior to the conditioning regimen for transplantation.[50]
with(MDS003) or without(MDS002) 5q deletion.

In MDS003, 148patients with the 5q deletion were
treated with lenalidomide 10mg daily for 21 or 28days
of a 28day cycle.[52] Most(73%) had failed prior
erythropoiesisstimulating agents(ESAs), and 74% had
no additional cytogenetic abnormalities. About 67%
of patients achieved transfusion independence, with a
median duration of response of>2years. Acomplete
cytogenetic response was achieved by 45% of evaluable
patients. In the MDS002 study,[53] 26% of patients
became transfusionindependent.
Immunomodulatory drugs
Lenalidomides development within lowrisk MDS

patients has been relatively rapid. The first MDS study,
MDS001, a phase I/II clinical trial of 43patients, 74%
of whom were transfusiondependent at study initiation,
and 12 of whom had the 5q deletion abnormality.[51]
Patients received lenalidomide at 10mg daily, 25mg
daily, or 10mg daily for 21days of a 28day cycle, and
49% had a major erythroid response, 83% of those
with 5q deletion. This prompted 2 phase II studies,
both for transfusiondependent, lowrisk MDS patients
On the basis of the available evidence, it is

recommended that patients with 5q deletion
128

High IPSS risk
Age 65-70 years or poor

performance status
Supportive care
Azacitidine
Poor risk
cytogenetics
Age <65-70 years or good

performance status
Available stem cell donor
No suitable stem cell donor
10% BM blasts, no
poor risk cytogenetics
<10% BM
blasts
Consider blast
reduction with
DNMT
inhibitors or
AML-like CT
Azacitidine
AML-like CT
OR
Azacitidine
Allogeneic SCT
10% BM
blasts
AML-like CT OR
Azacitidine
(within clinical
trial)
Allogeneic SCT
Figure3: Treatment algorithm for patients with higher risk myelodysplastic syndromes. BM, bone marrow; CT, chemotherapy; SCT, stem
cell transplantation
without additional chromosomal abnormalities or

excess blasts, with a low or intermediate1 IPSS
score and transfusiondependent anemia, who are
not candidates for treatment with or have failed a
therapeutic trial with hematopoietic growth factors,
should be offered lenalidomide.[52] The recommended
dose is 10mg given for 21days every 4weeks. The
median time to response is 6weeks and the dose
might be reduced to 5mg depending on tolerance.
Patients with 5q deletion and an intermediate1 IPSS
score due to additional chromosomal abnormalities
or an excess of blasts, who are not candidates for
treatment with or have failed a therapeutic trial
with hematopoietic growth factors, may be offered
lenalidomide within a clinical trial.[54] Patients with
5q deletion, a low or intermediate1 IPSS score,
and evidence of TP53 mutation have a significantly
higher risk of transformation to AML, which should
be considered in the choice between lenalidomide and
alternative therapeutic options.[18,55]
Hypomethylating agents
Two pyrimidine nucleoside analogs, 5azacytidine

and decitabine(5aza2deoxycytidine), have been
extensively investigated in clinical studies of patients
with MDS. The literature on the use of these agents
includes prospective randomized trials and prospective or
retrospective nonrandomized studies.[5860] Although the
Working Group agreed that it was not possible to draw a
definitive conclusion on the use of one drug with respect
to the other from the available evidence, the advantage
in overall survival reported for azacytidine makes this
agent preferable at present. On the basis of this evidence,
patients with IPSS intermediate2 or highrisk disease
who are not eligible for AMLlike chemotherapy and/
or allogeneic SCT should be treated with azacytidine.
In addition, fit patients with IPSS intermediate2 or
highrisk MDS and poorrisk cytogenetics who lack a
stem cell donor may receive treatment with azacytidine.
This agent may also be offered to fit patients without
poorrisk cytogenetics who lack a stem cell donor as an
alternative to remission induction chemotherapy. The
recommended azacitidine starting dose is 75mg/m2
injected subcutaneously for 7days(28day treatment
cycle) for a minimum of 6cycles.[61] Treatment should
be continued as long as the patient continues to benefit
or until disease progression.
It should be kept in mind that patients treated

with lenalidomide are at risk of cytopenias and
thromboembolic events. Patients should be monitored
for cytopenias, and given thromboprophylaxis with
aspirin or low molecular weight heparin.[56,57]
129
Myelodysplastic syndrome is a heterogeneous disease

and advances in its understanding and treatment
modalities are always in progress. The SMW will work
on regularly updating these published guidelines based
on international recommendations.
Immunosuppressive therapy
Immunosuppressive therapy with antithymocyte

globulin(ATG) plus 6months of oral cyclosporine
should be considered in patients younger than age
60years, with<5% marrow blasts, normal cytogenetics,
and transfusion dependency who are not candidates
for treatment with or for whom a therapeutic trial
with hematopoietic growth factors has failed.[62,63] The
use of ATG is highly recommended in the presence of
a hypoplastic bone marrow with normal cytogenetics
or trisomy 8.[62]
ACKNOWLEDGMENTS
This consensus meeting on MDS was sponsored by Algorithm
and Celgene.
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Remission induction chemotherapy
Induction chemotherapy should be considered for fit

patients without a suitable donor who are younger than
age 65-70years and have 10% or more bone marrow
blasts without adverse cytogenetic characteristics.
All patients who achieve complete remission after
induction chemotherapy should receive postremission
consolidation chemotherapy.[61]
Allogeneic stem cell transplantation
Recent data suggest that allogeneic SCT is feasible in

carefully selected patients older than 60years of age,
with acceptable morbidity and mortality.[64] Fit patients
up to age 65-70years with IPSS intermediate2 or high
risk and those with IPSS intermediate1 risk with excess
blasts or poorrisk cytogenetics are all candidates for
allogeneic SCT.
Cytoreductive(whether intensive or nonintensive)
therapy should be administered to those patients with
10% or more bone marrow blasts who are candidates
for allogeneic SCT. The use of hypomethylating
agents to prepare MDS patients with an excess of
marrow blasts for allogeneic SCT has been reported
in retrospective studies[65,66] and were being tested in
clinical trials. In the case of young and fit patients,
the evidence available so far does not allow firm
recommendation on the use of hypomethylating
agents for this purpose. However, in less young and
frail patients, hypomethylating agents are increasingly
used and may represent an option.
For MDS patients with a contraindication to a standard
myeloablative preparative regimen due to comorbidity,
reducedintensity or reducedtoxicity conditioning
allogeneic SCT should be considered, preferably within
a clinical trial.
CONCLUSION AND FUTURE PROSPECTIVE

These guidelines provide practice recommendations for
the diagnosis and management of patients with MDS.
They are adopted by the SMW based on international
practice guidelines and expert opinion.
130

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How to cite this article: Alaskar A, Al Momen AK, Al-Saeed A,

Al Sagheir A, Hanbali A, Al-Hejazi A, et al. Management of
myelodysplastic syndromes: Expert consensus opinion from the
Saudi MDS Working Group. J Appl Hematol 2014;5:123-32.
Source of Support: Nil, Conflict of Interest: None declared.
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However, unpublished data from previous experts

Myelodysplastic syndromes(MDSs) are a heterogeneous

The pathophysiology of MDS is a multistep process

Access this article online

Vol. 5 Issue 4 October-December 2014

Journal of Applied Hematology

Alaskar, etal.: Saudi MDS Working Group consensus opinion

Table1: Blood tests in the diagnostic workup of

A panel of Saudi hematologists representing the newly

WBC count with differential, RBC

WBC=White blood cell; RBC=Red blood cell; MCV=Mean corpuscular

Repeated bone marrow examinations are sometimes

It is quite important that the diagnostic procedures

Morphology(peripheral blood and bone marrow smears)

It is recommended to follow the World Health

A thorough physical examination should be performed.

Evaluation of bone marrow smears must include

The next diagnostic approach to suspected MDS

Blood test category

Note: An increase in white blood cell count with the

Vol. 5 Issue 4 October-December 2014

Alaskar, etal.: Saudi MDS Working Group consensus opinion

transformation especially that the monocytes might

Table2: New cytogenetic scoring system for

Bone marrow biopsy

A trephine biopsy should be performed in all cases

clinical suspicion is high for MDS, fluorescence

The best way of estimating cellularity is 100minus

Highresolution SNPs can now be applied in karyotypic

A cytogenetic analysis of bone marrow aspirate

In a recent study, the combination of metaphase

In the case of repeated failure of standard Gbanding

Journal of Applied Hematology

Alaskar, etal.: Saudi MDS Working Group consensus opinion

PTPN11), transcription factors and cofactors (NPM1,

requirements, the WHO prognostic scoring system

The IPSS classification was developed in 1997 and

Staging and prognostic scoring systems are

Table3: WPSS for MDS

Karyotypes: Good=Normal,Y, del(5q) only, del(20q) only;

Figure1: Distribution of different molecular markers in myelodysplastic

Journal of Applied Hematology

Vol. 5 Issue 4 October-December 2014

Alaskar, etal.: Saudi MDS Working Group consensus opinion

safe treatments capable of modifying the natural history

Table4: MPSS for lower risk MDS

Hematopoietic growth factors

Patients with IPSS low or intermediate1 risk, with

*Diploid and 5q only were favorable cytogenetics, all others were

Table5: IPSS for MDS

Although the scientific evidence on darbepoetin alfa

The available evidence does not allow any

Good=Normal, del(5q) only, del(20q) only,Y only; Poor=Very

Red blood cell transfusion and iron chelation therapy

The objective of RBC transfusion therapy is to improve

The Working Group stressed that the heterogeneity

Adult patients with primary MDS, low IPSS risk, and

Iron chelation should be considered in

Journal of Applied Hematology

Alaskar, etal.: Saudi MDS Working Group consensus opinion

Table6: IPSSR for MDS