MOSES

1. JOSEPH ADOMAKO
1

2. Define myelodysplastic syndromes
Outline the FAB and WHO classification systems for
myelodysplastic syndromes
Determine diagnostic criteria for myelodysplasia
2

3. Heterogeneous group of clonal disorders of
haemopoietic stem cells characterized by increasing
bone marrow failure in association with dysplastic
changes in one or more cell lineages.
3

4. Simultaneous proliferation and apoptosis of
haemopoietic cells leading to;
 Hypercellular bone marrow
 But peripheral cytopenia
Tendency to progress to acute myeloid leukaemia (AML)
4

5.  Primary – most cases
 Secondary - to chemotherapy and/or radiotherapy
 therapy‐related MDS (t‐MDS)
 t‐MDS is now classified with therapy‐related AML
 Annual incidence rate is about 3-4/100,000
 Increasing incidence with age till the 80s when its over 30/100,
000
 Rare in children
 Male to female ratio is about 1.4:1
5

6. Aetiology unknown. Postulates include
 ionizing radiation
 pesticides
 smoking etc
May follow exposure to cytotoxics
5q syndrome distinct form
6

7. 7

8. Shares features with:
 AML (Acute myeloid leukaemia)
 MPD (Myeloproliferative disease)
 AA (Aplastic anaemia)
 PNH (Paroxysmal nocturnal
haemoglobinuria)
 LGL (Large granular cell
leukaemia)
 PRCA (Pure red cell aplasia)
AML
PNH
MDS
AA
LGL MPD
8

9. Classified on the basis of the:
Blood count
Morphological appearance
Number of blast cells in blood or bone marrow
Genetic analysis
9

10.  Dysplasia may be present solely in a single lineage red cells
(refractory anaemia)
 Neutrophils or platelets – or present in two or more myeloid
lineages (refractory cytopenia with multilineage dysplasia;
RCMD)
 Erythroid dysplasia can also be associated with ring
sideroblasts
 Blast cell count is increased in the bone marrow, the diagnosis
is made of refractory anaemia with excess blasts (RAEB)
 Where the monocyte count is over 1 × 109/L the diagnosis
becomes chronic myelomonocytic leukaemia.
10

11. FIVE GROUPS:
Refractory Anemia (RA) <5% Blasts
RA with ≥15% ringed sideroblasts
RA with excess blasts (RAEB): 5-20% blasts
RA with excess blasts in transformation (RAEB-t): 21-
30% blasts
RA with excess blasts in chronic myelomonocytic
leukaemia
11

12. Refractory anaemia with unilineage dysplasia
Refractory anaemia (RA)
Refractory neutropenia (RN)
Refractory thrombocytopenia (RT)
Refractory anaemia with ring sideroblasts (RARS)
Refractory anaemia with excess blasts (RAEB)
Refractory cytopenia with multilineage dysplasia (RCMD)
MDS with isolated del (5q)
MDS unclassified
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
Chronic myelomonocytic leukaemia (CMML)
Atypical chronic myeloid leukaemia
Refractory anaemia with ring sideroblasts and thrombocytosis (RARST)
12

13. Chronic myelomonocytic leukaemia
(CMML)
Defined by a persistent monocytosis of more than 1.0 ×
×109/L with blasts <20% in the marrow
Dysplasia in other lineages
Negative for the BCR‐ABL1 translocation
Total white cell count is usually raised and may exceed 100
×109/L
Patients may develop skin rashes and around half have
splenomegaly
Bruising is frequent and gum hypertrophy
13

14.  Anaemia (mild to severe)
 Leucopenia – infections
 Thrombocytopenia - haemorrhage
 CMML is associated with;
 Splenomegaly
 Skin infiltration
 Serous effusion
14

15. Peripheral blood film
Red cells – anisopoikilocytosis, macrocytosis
Neutrophils – hypogranulation, pseudo-Pelger forms
Platelets- giant forms
Bone marrow
Erythroid cells – multinuclearity, nuclear budding,
ring sideroblast,
Myeloid cells – hypogranularity, increased blast cells
Megakaryocytes – giant forms/micromegakaryocytes
15

16. Cytogenetic abnormalities
 Monosomy 5/5q-
 Monosomy 7/7q-
 Trisomy 8
 Loss of Y chromosome
Mutation of genes encoding:
 Cell surface receptors (e.g KIT)
 Signal transduction proteins (e.g RAS)
 Transcription factors (e.g AML1)
16

17. 17

18. 18

19. 19

20. RED CELLS WHITE CELLS PLATELETS
Ovalomacrocytosis Hypogranularity Microcytosis
Dimorphic population Abnormal granulation Giant platelet granules
Megaloblastic change pseudo pelger-Huet Platelet dysfunction
Ring sideroblast Nuclear appendages Agranular platelets
Gross poikilocytosis Gross hypersegementation
Multinuclearity
Nuclear budding
20

21.  Myelodysplasia includes a group of clonal disorders of haemopoietic stem
cells that lead to bone marrow failure and low blood cell counts.
 A hallmark of the disease is the increased proliferation and apoptosis of
haemopoietic cells leading to the paradox of a hypercellular bone marrow but
pancytopenia.
 There is a tendency to progress to acute myeloid leukaemia.
 In most cases, the disease is primary but it may be secondary to
chemotherapy or radiotherapy given for treatment of another malignancy.
 The main clinical features of anaemia, infection and bleeding, are caused by
reduction in the blood count.
 Diagnosis is made by examination of the blood and bone marrow together
with cytogenetic and molecular studies