MYELODYSPLASTI

C SYNDROMES

DR MOHAMMAD ALMADY
ATTYA
LAB DIRECTOR AGH-HOFUF
M.D. , CLINICAL PATHOLOGY
LECTURER OF CLINICAL PATHOLOGY
FACULTY OF MEDICINE, ZAGZIG UNIVERSITY

MYELODYSPLASTIC SYNDROMES
(MDS)
Are a heterogeneous group of acquired , clonal stem
cell disorder which is characterized by:
Occurrence

mainly in elderly individuals,

uncommon in children

Dysplasia

of one or more hematopoietic cell lines

with resultant characteristic morphological
abnormalities

MYELODYSPLASTIC SYNDROME
(MDS)
Ineffective

erythropoiesis due to increased

apoptosis causing cytopenia of one or more cell
lines in peripheral blood

Increased

risk of transformation to acute myeloid

leukemia (AML)

Previously

called as dysmyelopoietic syndrome,

preleukaemic syndrome and oligoblastic leukemia

PATHOGENESIS OF MDS

MUTATION IN HAEMATOPOIETIC STEM CELL

ABNORMAL CLONE THAT PRODUCES FUNCTIONALLY AND STRUCTURALLY
DEFECTIVE BLOOD CELLS WITH SHORTENED SURVIVAL
IMMUNE DYSREGULATION
ABNORMAL MARROW

MICROENVIRONMENT

INEFFECTIVE ERYTHROPOIESIS, ENHANCED APOPTOSIS

GRADUAL EXPANSION OF ABNORMAL CLONE WITH SUPPRESSION OF NORMAL
HAEMATOPOIESIS NEW MUTATIONS
NEOPLASTIC TRANSFORMATION (ACUTE MYELOID LEUKAEMIA)

CAUSES OF MYELODYSPLASTIC
PRIMARY (Idiopathic)
SYNDROME
SECONDARY

-Prior to exposure to radiotherapy

-Prior to exposure to chemotheraphy
-Chemical exposure ( benzene, organic solvents)
-Genetic predisposition (Downs syndrome, Fanconis anaemia
Neurofibromatosis type 1)

CLASSIFICATION OF MDS
THERE ARE 2 CLASSIFICATION SYSTEMS FOR MDS

FRENCH-AMERICAN BRITISH(FAB)
CLASSIFICATION 1982

WORLD HEALTH ORGANIZATION (WHO)

CLASSIFICATION 2008

CATEGORY

FAB CLASSIFICATION AND

LABORATORY
FEATURES
BLASTS (Blood) BLASTS (Marrow)
RINGED
COMMENTS
(SIDEROBLAST)

1.
2.
3.
4.

5.

Refractory Anaemia
(RA)
RA with ringed
sideroblast (RARS)
Refractory Anaemia
with excess blasts
(RAEB)
Reractory Anaemia
with excess of blasts
in transformation
(RAEB-T)
Chronic
myelomonocytic
leukaemia

<1%

<5%

<15%

<1%

<5%

15%

<5%

5-20%

Variable

5%

21-30%

Variable

Auer rods

<5%

1-20%

Variable

Monocytosis >1000/cmm,
hepatosplenomegaly

Anaemia with dyserythropoiesis

predominant; macrocytosis
Dimorphic anaemia
Bi-or tri-cytopaenia,

WHO CLASSIFICATION 2008

CLINICAL FEATURES OF MDS

Usually

occurs in elderly persons >60 years of

age
Median age of diagnosis at 70 years old and is
more common in male
Uncommon in children
Patients present with symptoms related to
peripheral cytopaenias

There is fatigue, weakness ,dyspnea due to anaemia

There

is fever and infections due to neutropaenia

Easy

bruising, petechiae and other bleeding tendencies due to

thrombocytopaenia

Hepatosplenomegaly

 Significant

number of patients dont show any clinical

manifestations and are discovered incidentally on blood
examinations (by chance)

History

of treatment with chemotherapy or radiotherapy

LABORATORY FEATURES
PERIPHERAL BLOOD EXAMINATION
RED BLOOD CELLS
Anaemia is present in majority(80%) of patients.
Oval macrocytosis is a typical feature. Reticulocyte
count is low in relation to the level of anaemia.
Inappropriately low for degree of anaemia (R.P.I. <2%)

RETICULOCYTE COUNT
-Reticulocytes are young red cells that contain RNA remnants.
-RNA stains with supravital dyes such as brilliant cresyl blue or new
methylene blue with formation of blue precipitates or granules or
filaments.
-After smears are made on a glass slide, reticulocytes are counted
among 1,000 rbcs and the result is expressed as a percentage
-Reticulocyte count is performed to assess erythropoietic activity of the
bone marrow in case of anaemia

HOWELL JOLLY BODIES

MACROCYTOSIS

LABORATORY FEATURES

Reticulocytes : reticulocytes count can be expressed as follows:

1.

Reticulocyte count: this is the no. Of reticulocytes counted

among1000RBCs and expressed as a percentage.
Reticulocyte Count =Reticulocytes counted/ NO. Of RBC x 100

2.

Corrected reticulocyte count=reticulocyte count x pcv of patient in

%/average pcv for age

LABORATORY FEATURES
3. Absolute reticulocyte count: this is the no. Of
reticulocytes in 1 cmm of blood
Absolute reticulocyte count=retic precentage x red
cell count in million/cmm
4. Reticulocyte production index (R.P.I.)

MATURATION TIME IN DAYS

ACCORDING TO PCV:
PCV

> 35% : 1

PCV

25-35% : 1.5

PCV

15- 25% : 2

PCV

5-15% : 2.5

CLASSIFICATION OF ANAEMIA ACCORDING

TO RETICULOCYTE RESPONSE
RETICULOCYTE
RESPONSE

RPI (absolute retic.

ct)

CAUSES

1. Appropriate for the

degree of anaemia

2% (>100,000/ul)

Hyperproliferative
anaemias( Blood loss,
haemolytic anaemias)

2. Inappropriately low
for the degree of
anaemia

<2% (,75,000/ul)

Hypoproliferative
anaemias (IDA,
Megaloblastic anaemia,
Anaemia of chronic
disease, Thallassemias,
Endocrine diseases,
Sideroblastic anaemia,
Aplastic Anaemia,
MYELODYSPLASIA

PERIPHERAL BLOOD EXAMINATION

WHITE BLOOD CELLS
Neutropaenia is seen in (60%) of patients. Both immature and
abnormal granulocytes are present.
Neutrophils are typically hypogranular and hypolobulated(pseudo
pelger-huet abnormality). Type 1 (non-granular) and type
II(granular) blasts may be seen

PERIPHERAL BLOOD EXAMINATION

PLATELETS
Thrombocytopaenia is seen in one half of patients. Bleeding time is
prolonged despite normal platelet count(due to platelet function
defect).Other abnormalities include agranular platelets, giant platelets,
micromegakaryocytes and megakaryocte fragments.

BONE MARROW BIOPSY

Necessary

for the assessment of cellularity

Immature

cells such as myeloblasts and promyelocytes

are present in the center of the marrow spaces from the
vascular structure rather than the long endosteum. This
has been called abnormal localisation of immature
precursor (ALIP). It is a feature of high grade
lesion such as RAEB. ALIP is associated with
increased risk of progression to AML.

Bone

marrow fibrosis which is more common in

secondary MDS is assessed on bone marrow biopsy

CYTOGENETIC ANALYSIS

Non-random, clonal chromosomal abnormalities are observed in

50% of patients with primary MDS and in 80% of patients with
secondary MDS.
In contrast to AML, chromosomal abnormalities in MDS are
numerical (i.e. Loss or gain of chromosomal material) rather than
structural
(i.e. Translocations)

COMMON CYTOGENETIC ABNORMALITIES INCLUDE:

-5,-5q,-7,-7q,20q-,+8,loss OF X OR Y CHROMOSOME AND 17pPresence of a clonal chromosomal abnormality strongly favours the
diagnosis of MDS over reactive conditions

Patients of MDS who have complete chromosomal abnormalities (i.e.

Abnormality of >3chromosomes have poor prognosis with increased risk
of progression to AML
Patients with normal or near normal karyotype have better survival

Certain cytogenetic abnormalities are associated with distinctive and

haematological features
5q- abnormality: main occurrence in elderly women, presence of
monolobulated megakaryocytes in bone marrow, increased platelets with
giant forms, macrocytic anaemia and favourable prognosis

DIFFERENTIAL
DIAGNOSIS
In

elderly subjects with RA, megaloblastic anaemia due to

nutritional deficiency (VIT B12 or folate ) should be excluded
since morphological features in both conditions are similar

Therapeutic

trial should be given even if vitamin levels are normal

Other causes of dyshaematopiesis which should be distinguished

are exposure to toxic chemicals, heavy metals, chemotherapy,
inflammatory or neoplastic disease, alcohol induced sideroblasic
anaemia and HIV infection

 MDS

should also be distinguished from aplastic anaemia if bone

marrow is hypocellular, congenital dyserythropoeitic anaemia in
children and acute myelomonocytic leukaemia

PROGNOSIS
All

patients with MDS have reduced life expectancy as compared to

age and sex matched controls.

A Scoring system based on number of blasts in bone marrow,

karyotype and cytopaenias has prognostic importance

Apart

from transformation to AML, patients may die from

complications of cytopaenias ( infections , bleeding) or from
unrelated disease

TREATMENT

Patients

with RA and RARS have low incidence of

AML tranformation while patients with RAEB-1 and
RAEB-2 have higher incidence of transformation to
AML. However, even in the absence of progression to
AML, patients have increased morbidity and mortality
due to complications related to various cytopaenias .

 Supportive

therapy

Hypomethylating

agents

Lenalidomide
Immunosuppressive
High

therapy

dose AML like chemotherapy

Haematopoietic

stem cell transplantation

THANK
THANKYOU!!!
YOU!!!