Myelodysplastic Syndrome

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

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TYPE BM Blasts Peripheral blood blasts Auer Rods Monocytes gt 1000 /uL Ringed Sideroblasts gt15
RA lt5 lt1 No No No
RAS lt5 lt1 No No Yes
RAEB 5-20 lt5 No No -
CMML lt20 lt5 No Yes -
RAEB-T 21-30 gt5 - - -
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Prevalence

• 10,000 cases annually in US
• 4.1 MDS / 2.1 AML per 100,000
• Risk of Development increases w/ Age
• Unusual lt50yrs, unless tx induced
• Median age 65 or greater, w/ male predominance

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Predisposing Elements

• Heritable Genetic Disorders including Downs,
  Congential Neutropenias, Fanconis Anemia, Ataxia
  Telangiectasia, NF-1.
• Acquired Mutagen Exposure (alkylators, Topio
  II, Radioactive), Hemapoietic cell xplants,
  environmental exposures, Aplastic Anemia, PNH,
  Polycythemia Vera

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Clinical Presentation

• Non-specific and Varied
• Most asymptomatic and Dx found on labs
• Fatigue, dizziness, weakness, dont 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

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Physical Findings

• 60 Pale
• 26 Petechaie and/or Purpura
• HSPM and lymphadenopathy are uncommon save for
  CMML
• Cutaenous Manifestations uncommonbut 2
  recognized syndromes can occur in MDS
• --gt Sweets acute febrile neutrophilic
  dermatosis
• --gt Myeloid Sarcoma chloroma

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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
• lt5 have isolated neutropenia or thrombocytopenia
  w/o anemia

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Differential Dx

• Megaloblastic Anemia
• Aplastic Anemia
• Myelofibrosis
• Atypical CML
• HIV
• Medications (VPA, Cellcept, Ganciclovir)
• Etoh

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Our Patient

• Immunoglobin Production variably
  affectedHypogammaglobulinemia 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 lt5 BM blasts, gt15 ringed sideroblasts,
  accounts for 17 of MDS

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Ringed Sideroblasts