












































International Journal of Cancer Therapy and Oncology
www.ijcto.org

Corresponding author: Ashok Komaranchath; Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India.
Cite this article as: Lingegowda A, Kuntegowdenahalli L, Komaranchath A, Devi L, Kumari P, Kamath M. An analysis of the demographic profile, clinical
manifestations, investigations and outcome of paediatric myelodysplastic syndrome: A single centre, cross-sectional study. Int J Cancer Ther Oncol 2015;
3(3):337. DOI: 10.14319/ijcto.33.7

© Lingegowda et al. ISSN 2330-4049

An analysis of the demographic profile, clinical manifestations,
investigations and outcome of paediatric myelodysplastic

syndrome: A single centre, cross-sectional study
Appaji Lingegowda1, Lakshmaiah Kuntegowdenahalli2, Ashok Komaranchath2, Lakshmi Devi3,

Prasanna Kumari3, Mangesh Kamath2

1Department of Pediatric Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
2Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India

3Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, India

Received February 19, 2015; Revised March 10, 2015; Accepted April 05, 2015; Published Online June 04, 2015

Original Article

Abstract
Purpose: Pediatric myelodysplastic syndrome (MDS) is a relatively rare entity, with distinct clinical features and more ag gres-
sive course than its adult counterpart. The aim of this study was to analyze the incidence of pediatric myelodysplastic syndrome
at a tertiary cancer care center in southern India along with clinical manifestations, investigations and outcome. Methods: On
retrospective analysis of 1094 cases of pediatric hematological malignancies over a five-year period from September 2009 to
August 2014, a total of seven cases of pediatric myelodysplastic syndrome were identified. Presenting complaints, physical ex-
amination, investigations including haemogram, biochemistry, bone marrow examination and cytogenetics were reviewed. The
diagnosis of MDS was made if there was dysplasia in at least 10% of cells in two or more cell lineages. All patients were ris k
stratified using the revised IPSS. Results: Out of 1094 cases of pediatric hematological malignancies presenting at our institute
within the study period, there were only seven cases of pediatric MDS with an incidence of 0.65%. There were no genetic pre-
dispositions nor any cases of therapy related MDS. The most common presentation was with fever and all patients had signif i-
cant splenomegaly. All patients had anemia (Median-6.2 gm / dL) with elevated WBC counts (Median-30,900 / uL) and throm-
bocytopenia (Median-50,000 / uL). The marrow cytogenetics was normal in five patients. Most patients fell into the high and
very high-risk category of the revised IPSS, with only two patients of low risk. All seven patients were given only supportive
care but one progressed to AML for which he was treated with remission induction. Only two patients were alive at the time of
analysis and median survival was 9 months. Conclusion: Pediatric MDS is a rare disease with a short clinical history, aggressive
course and generally poor outcomes as compared to the adult variant. A hematopoietic stem cell transplant may be the only
viable option for survival.

Keywords: Pediatric Myelodysplastic Syndrome; MDS

Introduction
The myelodysplastic syndrome (MDS) represents a hetero-
geneous group of stem cell malignancies characterized by
dysplastic and ineffective hematopoiesis and a variable risk
of transformation to acute leukemia. Myelodysplastic syn-
drome in the pediatric age group is uncommon and consti-
tutes a distinct entity different in many ways from adult
MDS. They have certain unique clinical features, a more
aggressive clinical course with a shorter overall survival.
Epidemiological data for pediatric MDS is limited not only
because it is relatively rare, but also because of the difficulty
in diagnosis as well as classification. However, there have
been several case series of pediatric MDS reported.1-9 The
largest series was from Japan by Sasake et al. who submitted

a retrospective analysis of 189 patients of MDS less than 16
years of age from sixty-two centers in Japan over a period of
7 years. There has been only one such study from India, by
Chatterjee et al. where 21 patients with MDS from northern
India aged less than 17 years were evaluated.10 Compared to
this study, the median age of presentation was lower in our
institution (4 years vs. 9 years). All patients presented with
pallor and a majority had fever and bleeding diathesis. The
overall survival was dismal and the best prognosis appeared
to be for those with refractory cytopenias with a low blast
count. We have classified our patients on the basis of both
the type of MDS as well as the revised IPSS scoring system.

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2 Lingegowda et al.: Demographic profile and outcome of pediatric MDS International Journal of Cancer Therapy and Oncology
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© Lingegowda et al. ISSN 2330-4049

Consensus on the treatment of pediatric MDS is also uncer-
tain, with allogenic stem cell transplant the only chance of
cure. Chemotherapy is reserved for patients in more ad-
vanced stage of the disease. The newer hypomethylating
agents used in adult MDS have not yet been approved in
pediatric MDS. Here, we present our institution’s experience
with pediatric MDS, where we had seven cases over a
five-year period from September 2009 to August 2014. We
have analyzed their demographic profile, presenting fea-
tures, clinical findings, investigative reports, treatment and
outcome.

Methods and Materials
On retrospective analysis of 1094 cases of pediatric hemato-
logical malignancies over a five year period from September
2009 to August 2014, a total of seven cases of pediatric
myelodysplastic syndrome were identified of which there
were 4 boys and 3 girls with a median age of 4 years. Pre-
senting complaints, physical examination, investigations
including haemogram, biochemistry, bone marrow examina-
tion and cytogenetics were analyzed. The patients were clas-
sified according to the pediatric adaptation of the 2008 WHO
classification of myelodysplastic syndromes. Four patients
were classified as RAEB of which one patient progressed to
RAEB-T and finally to acute myeloid leukemia. He had a
total WBC count >100,000/uL, 13% blasts in bone marrow at
presentation, Trisomy 8 on karyotyping and R-IPSS score of
6.5 (very high). The other three patients were classified as
RCC. There were no predisposing syndromes nor any cases
of therapy related MDS. All patients were risk stratified us-
ing the revised IPSS. All patients had fever and splenomegaly
on presentation, and only one patient presented with bleed-
ing diathesis. Anemia and thrombocytopenia were present in
all patients and all except two patients had normal cytoge-
netics. Treatment was mainly supportive. The one patient
who progressed to RAEB-T was treated with a standard 7+3
remission induction protocol, but failed to achieve remission
and progressed to acute myeloid leukemia with 90% blasts in
peripheral blood. Outcome was measured by calculating
median overall survival.

Results
A total of seven patients were identified with pediatric
myelodysplastic syndrome. On comparison, this constituted
only around 0.65% of all pediatric hematological malignan-
cies at our institute.

Patient profiles
There were four boys and three girls with ages ranging from
2 years to 14 years with a median age of 4 years. There were
4 patients classified as RAEB and 3 as Refractory Cytopenia
of childhood (RCC) as per the Revised WHO Classification
of Childhood Myelodysplastic Syndromes (2008). There were
no constitutional predispositions like Down’s syndrome,

Fanconi’s anemia, Pearson’s syndrome, etc. There were no
cases of therapy related MDS either.

Clinical presentation
All seven patients had fever as a presenting complaint, three
had abdominal pain and distension, one presented with
bleeding from the gums and one had recurrent vomiting.
The median duration of symptoms were 21 days with a range
of 10 to 60 days. All patients except one had a performance
status </= 2. Six of the patients had clinical pallor and two
patients had palpable lymphadenopathy. All seven patients
had palpable splenomegaly and a mean spleen size of 3.8 cm
under the left costal margin. Three of these patients also had
palpable hepatomegaly. (Chart 1)

CHART 1: Presenting complaints (No. of patients with the men-
tioned presenting complaint).

Investigations
Six of the patients had a hemoglobin of less than 10 g/dl and
mean hemoglobin was 7.2 g/dl. Total WBC count was also
elevated in most cases with a median count of 30900/uL.
Platelet counts were also low, ranging from 12000/uL to
128,000/uL with a median value of 50000/uL. Renal and liver
function tests were normal in all seven cases. There were
bone marrow blasts ranging from 6% to 15% at presentation
in four cases and <1% blasts in the other three. Another
finding that suggested a high burden of disease was a high
LDH value, which was seen in all seven cases ranging from
392-2780 IU/L with a mean value of 1238 IU/L. (Table 1)

Cytogenetics
Bone marrow cytogenetics were done on all seven patients
and showed a normal karyotype in five patients. One patient
had trisomy 8 and another had monosomy 7 (Chart 2). There
were no complex cytogenetic abnormalities.

CHART 2: Cytogenetics (No. of patients with the mentioned cyto-
genetic abnormality).



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© Lingegowda et al. ISSN 2330-4049

TABLE 1: Patient characteristics.
Sl.
No.

Age
/Sex

Hb. TLC PLT BM
Blasts(%)

LDH Cytogenetics Classification

1 5/F 8.3 6000 50000 6 1050 Monosomy 7 RAEB
2 13/M 5.9 30900 27000 <2 1090 Normal RCC
3 14/M 6.2 2500 128000 <2 2780 Normal RCC
4 4/M 9.8 >100000 60000 13 1103 Trisomy 8 RAEB
5 2/F 3.6 34900 26000 15 1300 Normal RAEB
6 3/F 6.1 >100000 124000 <2 392 Normal RCC
7 3/M 10.8 22700 12000 12 950 Normal RAEB

CHART 3: Revised IPSS score (No. of patients in each risk group).

Risk stratification
Risk stratification was done using the revised IPSS, which
takes into account cytogenetics, bone marrow blast percent-
age, hemoglobin, platelet count and absolute neutrophil
count at the time of presentation. The median R-IPSS score
was 5.0 (high risk), with 2 very high, 2 high, 1 intermediate
and 2 low risk groups (Chart 3).

Outcome
None of the patients were willing for either intensive chem-
otherapy or stem cell transplant initially and were started on
best supportive care with repeated transfusion of blood
products, antibiotics and other measures. Out of the seven
patients, one progressed on follow-up to acute leukemia with
more than 20% blasts and was given remission induction
chemotherapy with a standard 7 + 3 protocol with Cytara-
bine and daunorubicin. The patient however, failed to
achieve remission with the same and was continued on best
supportive care as he was not affordable for high dose chem-
otherapy and stem cell transplant.

On follow up of the patients, the survival ranged from 1-49
months with a median survival on 9 months. Five of the
seven patients died due to various complications. One pa-
tient died from pneumonia, four from bleeding diathesis, out
of which one was the patient who had progressed to AML
and had received remission induction. Two of our patients
were alive at the end of the study period, of which one had
survived for 49 months. Of note is that this patient presented
with normal leucocyte counts, platelet count of more than

100,000/uL, occasional bone marrow blasts, normal cytoge-
netics and had the lowest R-IPSS score of 2.5 among all the
patients. He is also transfusion free for the past 2 years.

Discussion
Although myelodysplastic syndrome is predominantly a dis-
ease of the elderly, there has been several case series de-
scribing this disease in children. In general, MDS is an un-
common disease with an incidence ranging from 4.1 per
100,000 11 to 1.24 per 100,000 in recent series 12. The inci-
dence is considerably lower in children with Hasle et al.
describing it as 3.4 in 1,000,000 in children less than 15 years
of age.2 A population based survey from Denmark had simi-
lar values of incidence which set the number of pediatric
MDS at around 2-3% of all pediatric hematological malig-
nancies.2, 13 There have been no epidemiological studies for
childhood MDS in southern India. Acute leukemias account
for approximately 35-45% of the almost 50,000 childhood
malignancies in India 14 and in our center, out of the 1094
cases of pediatric hematological malignancies over the past 5
years, we have seen only seven cases of childhood MDS with
an incidence of 0.65%. This incidence appears to be much
lower than that seen in most western countries and we be-
lieve it may be due to both misdiagnoses and possibility of
late presentation of several cases as frank AML. Almost 60%
of our patients presented in an advanced stage of disease
with excess blasts and a high R-IPSS score (Median of 5.0).
They also appeared to have a higher burden of disease with
high LDH levels and all patients had anemia and thrombo-
cytopenia. Marrow cytogenetic analysis showed normal cy-



4 Lingegowda et al.: Demographic profile and outcome of pediatric MDS International Journal of Cancer Therapy and Oncology
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© Lingegowda et al. ISSN 2330-4049

togenetics in five patients and only two patients showing
cytogenetic abnormalities.

Due to financial constraints, none of our patients could af-
ford stem cell transplants and only one was treated aggres-
sively because of progression of disease. As per the
EWOG-MDS 98 study by Strahm et al. the 3-year disease
free survival of hematopoietic stem cell transplant is around
50%.15 The one patient who received chemotherapy did not
achieve remission and eventually succumbed to the disease.

In a trial comparing the outcome of chemotherapy in MDS
versus acute myeloid leukemia, less than 30% of pediatric
MDS patients survived for more than 3 years.16 The overall
survival was dismal, with a median OS of only 9 months.

In view of the several differences between pediatric and
adult MDS (Table 2) 17, the WHO classification, which was
developed based on adult cases, is considered inadequate for
classifying pediatric MDS.

TABLE 2: Differences between adult and pediatric MDS.17

FEATURE ADULT MDS PEDIATRIC MDS
Refractory Anemia (RA) - Anemia Always Present Not always present (44% can have Hb levels >10g/dL)
RA-Significant dyserythropoiesis Always present May be subtle and overlooked
RA-Course Protracted (Median

survival 66 months)
Transformation to AML or more aggressive form of MDS occurs
with short lag time

Refractory anemia with ringed
sideroblasts

Constitutes 10-12% of cases Exceedingly rare

MDS assoc. with isolated 5q
deletion

Occurs predominantly in
middle age to older women

Not described

Constitutional abnormalities Rare Often observed
Incidence More common Rare
Clinical Features

)a(Symptoms
)b(Signs

Majority are asymptomatic Majority symptomatic
Hepatosplenomegaly and granulocytic sarcoma more prevalent

Prognosis Relatively good to poor Poor even in RA
Role of IPSS for predicting
outcome

Significant role Only cytogenetic pattern is of prognostic value

Cytogenetics
Most conspicuous difference

Monosomy 7

-5,-5q,-Y
-7q, +8(trisomy 8)

Constitutional genetic
abnormalities rare
Noted in <5% of Adult RA

Commonly present
Rare

35% carry constitutional genetic abnormalities

Most common cytogenetic abnormality in refractory cytopenias
of children
Common
Commonest abnormalities are monosomy 7 and trisomy 8

TABLE 3: Pediatric adaptation of the 2008 WHO classification.19

Myelodysplastic syndromes
Refractory cytopenias (Blood blasts <2%, bone marrow
blasts <5%).
Refractory anemia with excessive blasts (Blood blasts
<2%, bone marrow blasts <5%-19%).
Refractory anemia with excess blasts in transformation
(Bone marrow blasts 20-29%) or Acute myelogenous
leukemia with MDS-related changes (Peripheral blood
or marrow blasts >20%).

Myelodysplastic/myeloproliferative disease
Juvenile myelomonocytic leukemia

Down syndrome disease
Transient abnormal myelopoiesis
Myeloid leukemia of Down Syn-
drome

To overcome this, Hasle et al. had proposed a pediatric ap-
proach to the WHO classification, which emphasizes the
subtypes found in pediatric age group and deleting some of
the adult subtypes, which are rare or unseen in the pediatric
population. The WHO pediatric modification was first pro-
posed in 2003 18 and later modified in 2008. Presently, the
pediatric WHO adaptation defined in 2008 (Table 3)19 is be-
ing used worldwide and applies to more than 99% of all
childhood MPD cases.

In the revised WHO (2008) classification, the MDSs were
further subdivided into refractory cytopenia, refractory
anemia with excess blasts (RAEB), and refractory anemia
with excess blasts in transformation (RAEB-t) and has a sep-
arate section on childhood MDS, where JMML and ML-DS
are distinct disorders. This update also defines the criteria for
defining refractory cytopenia of childhood (RCC). Children
with <2% blasts in blood, <5% blasts in the bone marrow,
and persistent cytopenias associated with dysplasia in at least
two cell lines are included in this group. Treatment of adult



Volume 3 • Number 3 • 2015 International Journal of Cancer Therapy and Oncology 5
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© Lingegowda et al. ISSN 2330-4049

MDS with hypomethylating agents have shown great prom-
ise, but these agents are yet to be tried in the pediatric set-
ting. Considering the poor prognosis in children trials with
these newer agents may be warranted.

Conclusion
Even though myelodysplastic syndrome is rare in childhood,
the diagnosis must be kept in mind when children present
with refractory cytopenias and a short symptom duration.
Pediatric MDS is very different from that of the adult variant
in presentation, clinical features, cytogenetics and survival.
The age of presentation was lower than that found by Chat-
terjee et al. in northern India. They present with a shorter
history and are more likely to have multilineage dysplasia. In
our series, there were only 2 patients with cytogenetic ab-
normalities with all others having normal karyotypes. The
clinical course is more aggressive and they tend to have
shorter survivals as compared to adult MDS. Hence, early
diagnosis and management is essential. Median survival in
our series was similar to that of western data which showed
a median survival of 9 months. Outcome with supportive
care alone is dismal. A hematopoietic stem cell transplant
may be the only viable option and should be performed early
in the course of disease. The use of hypomethylating agents
in pediatric MDS needs to be evaluated further.

Conflict of interest
The authors declare that they have no conflicts of interest.
The authors alone are responsible for the content and writ-
ing of the paper.

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