1. Myelodysplastic Syndrome
“brief overview”

2. Intro
MDS comprises a group of malignant stem cell disorders characterized by ineffective blood cell production and variable risk of transformation to acute leukemia.

3. MDS subtypes Refractory Anemia 21% (RA)
RARS (refractory anemia w/ ringed sideroblasts 17%)
RA w/ excess blasts 37% (RAEB)
RA w/ excess blasts in transformation 12% (RAEB-T)
CMML (chronic myelomonoctic leukemia) 13%

4. RA <5 <1 No RAS Yes RAEB 5-20 +- CMML <20 RAEB-T 21-30 >5
TYPE
BM Blasts%
Peripheral blood blasts %
Auer Rods
Monocytes > 1000 /uL
Ringed Sideroblasts >15% RA
<5
<1 No
RAS
Yes
RAEB
5-20 +-
CMML
<20
RAEB-T
21-30
>5

5. Prevalence ~ 10,000 cases annually in US 4.1 MDS / 2.1 AML per 100,000
Risk of Development increases w/ Age
Unusual <50yrs, unless tx induced
Median age 65 or greater, w/ male predominance

6. Predisposing Elements
Heritable – Genetic Disorders including Down’s, Congential Neutropenias, Fanconi’s Anemia, Ataxia Telangiectasia, NF-1….
Acquired – Mutagen Exposure (alkylators, Topio II, Radioactive), Hemapoietic cell xplants, environmental exposures, Aplastic Anemia, PNH, Polycythemia Vera

7. Clinical Presentation
Non-specific and Varied
Most asymptomatic and Dx found on labs
Fatigue, dizziness, weakness, “don’t feel well”
Less commonly Infxn, bleeding, bruising
Fever and wgt loss uncommon
Infxn is principal cause of death in MDS (neutropenia and granulocyte dysfunction)
Also rarely AI manifestations can occur

8. Physical Findings 60% Pale 26% Petechaie and/or Purpura
HSPM and lymphadenopathy are uncommon save for CMML
Cutaenous Manifestations uncommon…but 2 recognized syndromes can occur in MDS
--> Sweet’s – acute febrile neutrophilic dermatosis
--> Myeloid Sarcoma – “chloroma”

9. Laboratory
Bone Marrow and Blood changes variable, divided into FAB MDS subtypes.
Chromosomal Abnormalities are associated as well.
Anemia almost always present w/ low retic response
Pancytopenia in up to 50% of cases
<5% have isolated neutropenia or thrombocytopenia w/o anemia

10. Differential Dx Megaloblastic Anemia Aplastic Anemia Myelofibrosis
Atypical CML
HIV
Medications (VPA, Cellcept, Ganciclovir)
Etoh

11. Our Patient…
Immunoglobin Production variably affected…Hypogammaglobulinemia 13%, polyclonal Hypergammaglobulinemia 30%, Monoclonal Gammopathy reported in 12% of patients
Lymphopenia largely 2/2 to reduced CD4+ cells inversely related to # of transfusions received.
RARS: <5% BM blasts, >15% ringed sideroblasts, accounts for ~17% of MDS

12. Ringed Sideroblasts