1. Myelodysplastic Syndrome

2. Myelodysplastic Syndrome
Group of clonal disorders of hematopoietic stem cells characterized by cellular dysplasia and ineffective hematopoiesis
Results in cytopenias and dysmyelopoiesis
Variable risk of transformation to acute leukemia

3. Pathophysiology Primary MDS or Secondary MDS
A clonal mutation in hematopoietic stem cells
Bone marrow failure due to ineffective hematopoiesis
Increased cytokines (TNF-a) inhibit hematopoiesis
Increased apoptosis
Results in futile cycling of blood cells with impaired production of mature blood cells

4. Prevalence
Mainly a disorder of older patients, rarely presents before age 50
Median age is 65 years
Male predominance

5. Clinical Presentation
Non specific signs and symptoms of various cytopenias
Fatigue, SOB, exercise intolerance, pallor, tachycardia
Mucosal bleeding, petechiae, ecchymoses
Infection, fever
B-symptoms are uncommon
Splenomegaly and lymphadenopathy are rare

6. Diagnosis Anemia uniformly present with decreased reticulocytosis
>50% present with pancytopenia
50% present with associated neutropenia
<5% isolated neutropenia or thrombocytopenia
Cytopenia with normal or hypercellular bone marrow with single or multi-lineage dysplasia

7. Morphology
Peripheral changes include oval macrocytic red cells, hypogranular granulocytes with the pseudo-Pelger–Huët anomaly, and giant platelets.

8. Morphology
Megaloblastic red-cell precursors with multiple nuclei or asynchronous maturation of the nucleus and the cytoplasm

9. Morphology
Ringed sideroblasts, erythroid precursors with iron-laden mitochondria

10. Classification Refractory Anemia (RA)
Disease
Peripheral Blood
Bone Marrow
Refractory Anemia (RA)
Anemia
No or rare blasts
Erythroid dysplasia only
< 5% blasts
< 15% ringed sideroblasts
Refractory Anemia with Ringed Sideroblasts (RARS)
No blasts
>15% ringed sideroblasts < 5% blasts
Refractory cytopenia with multilineage dysplasia (RCMD)
Cytopenia
No Auer rods
< 1 × 109/L monocytes
Dysplasia in 10% of cells in 2 or more myeloid cell lines < 5% blasts in marrow < 15% ringed sideroblasts

11. Classification Cont.
Disease
Peripheral Blood
Bone Marrow
Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)
Cytopenia
No or rare blasts
No Auer rods
< 1 × 109/L monocytes
Dysplasia in 10% of cells in 2 or more myeloid cell lines < 5% blasts in marrow > 15% ringed sideroblasts
Refractory anemia with excess blasts-1 (RAEB-1)
Cytopenias
< 5% blasts
Unilineage or multilineage dysplasia
5% to 9% blasts
Refractory anemia with excess blasts-2 (RAEB-2)
5% to 19% blasts
Auer rods ±
 < 1 × 109/L monocytes
10% to 19% blasts
±Auer rods 

12. Classification cont. Disease Peripheral Blood Bone Marrow
Myelodysplastic syndrome, unclassified (MDS-U)
Cytopenias
No or rare blasts
No Auer rods
Unilineage dysplasia in granulocytes or megakaryocytes
< 5% blasts
MDS associated with isolated del(5q)
Anemia
Platelets normal or increased
Normal to increased megakaryocytes with hypolobated nuclei
Isolated del(5q)