Classification, Clinical features, Diagnosis, and Treatment of Myelodysplastic Syndrome

1. MYELODYSPLASTIC SYNDROMES
Dr Dilmo Yeldo
DNB General Medicine Resident

2. INTRODUCTION
• Myelodysplastic syndromes (MDSs) are a very complex
group of myeloid disorders characterized by peripheral
blood cytopenias and morphologic evidence of dysplasia
in bone marrow.
• The natural history of patients with MDS is also very
heterogeneous with a small subgroup of patients
surviving for long periods of time even with minimal
intervention and other patients with very poor prognosis
succumbing early to the disease either from complications
of infections or bleeding or from transformation to AML.

3. ETIOLOGY AND PATHOPHYSIOLOGY
• MDS is a clonal hematopoietic stem cell disorder
characterized by disordered cell proliferation and impaired
differentiation, resulting in cytopenias and risk of
progression to leukemia.
• MDS is a disease of the elderly; the mean age at onset is
older than 70 years.
• Both chromosomal and genetic instability have been
implicated: both are aging-related.
• MDS can be the result of toxic exposure of bone marrow
stem cells.

4. • Recurrent somatic mutations, acquired in the abnormal
marrow cells which is absent in germline also plays a role.
• A number of epidemiologic studies have suggested that
environmental factors play a role in the development of
MDS.
• A number of genetic syndromes (associated with bone
marrow failure) are associated with the development of
MDS.
• Syndromes in this category include Diamond–Blackfan
anemia, Shwachman– Diamond syndrome, dyskeratosis
congenita, cartilage hair hypoplasia, and Treacher Collins
syndrome.

5. MOLECULAR PATHOGENESIS

7. CLASSIFICATION

8. CLINICAL FEATURES
• Anemia dominates the early course.
• Most symptomatic patients complain of the gradual onset
of fatigue and weakness, dyspnea, and pallor, but at least
one-half of patients are asymptomatic, and their MDS is
discovered only incidentally on routine blood counts.
• Previous chemotherapy or radiation exposure is an
important historic fact.
• Children with Down syndrome are susceptible to MDS as
well as leukemia.
• A family history may indicate a hereditary form of
sideroblastic anemia or Fanconi anemia.

9. INVESTIGATIONS
BLOOD
• Anemia, Bicytopenia, Pancytopenia, Isolated
neutropenia, Thrombocytopenia.
• Macrocytosis is common
• Platelets also are large and lack granules.
• Neutrophils are hypo-granulated, hypo-segmented,
ringed, contain Döhle bodies.
• Circulating myeloblasts usually correlate with marrow
blast numbers, and their quantity is important for
classification and prognosis.

10. BONE MARROW
1. The bone marrow is usually normal or hypercellular or
rarely hypocellular also.
2. Dyserythropoietic changes (nuclear abnormalities) and
ringed sideroblasts in the erythroid lineage
3. Hypogranulation and hyposegmentation in granulocytic
precursors, with an increase in myeloblasts
4. Megakaryocytes showing reduced numbers
5. Megaloblastic nuclei and defective hemoglobinization in
the erythroid lineage are common.
6. Cytogenetic analysis and fluorescent in situ hybridization
can identify chromosomal abnormalities.

11. DIFFERENTIAL DIAGNOSIS
• Vitamin B12, Folate or Vitamin B6 deficiency
• Copper deficiency can lead to cytopenias and dysplastic
marrow.
• Marrow dysplasia can be observed in acute viral
infections, drug reactions, or chemical toxicity.
• Idiopathic cytopenia of unknown significance(ICUS)
• The WHO considers 20% blasts in the marrow as the
criterion that separates AML from MDS.

12. PROGNOSIS

14. CAUSE OF DEATH

15. TREATMENT
• Supportive care is an integral part of the care for
patients with both lower and high-risk MDS.
• The most frequent events associated with death were
infectious and bleeding complications
• Three major approaches are considered as supportive
care measures in MDS. These include:
1. Transfusions of red cells and/or platelets
2. The use of prophylactic antibiotics
3. The use of growth factors support.

16. • Only Hematopoietic stem cell transplantation offers cure
of MDS(fraction of patients). The survival rate in selected
patient cohorts is ~50% at 3 years but improving.
• Iron chelating Agents like oral Deferasirox helps in iron
overload due to repeated blood transfusions and also
associated with significant clinical improvements in
patients undergoing stemcell transplantation.
• The hypomethylating agents like azacitidine and
decitabine are the standard of care for patients with
high-risk MDS.
• Lenalidomide, a thalidomide derivative with a more
favorable toxicity profile, is particularly effective in
reversing anemia in MDS patients with 5q– syndrome

17. • Immunosuppression also may produce sustained
independence from transfusion and improve survival.
• ATG, cyclosporine, and the anti-CD52 monoclonal
antibody (alemtuzumab) are especially effective in
younger MDS patients (<60 years old) with more favorable
IPSS scores and who bear the histocompatibility antigen
HLA-DR15.
• EPO alone or in combination with G-CSF can improve
hemoglobin levels

19. THANK YOU