Myelodysplastic Syndromes (MDSs) Flashcards
Group of acquired clonal hematologic disorder that affect maturation of erythroid, myeloid, and/or megakaryocytic lines
- PROGRESSIVE PB CYTOPENIAS (MAY EVENTUALLY PROGRESS TO AML)
Myelodysplastic Syndromes (MDSs)
Mechanism of MDSs
Hypomethylation of DNA followed by hypermethylation of DNA
Which MDS mechanism leads to reduced transcription leading to cytopenias?
Hypomethylation of DNA
Which MDS mechanism leads to enhanced transcription leading to an acute leukemia (usually AML)
Hypermethylation of DNA
MDS PB findings
- Cytopenias
- Anemia (N/N or macrocytic anemia)
- Dysplasia
MDS BM findings
- Hypercellular
- Dysplasia
- Ineffective hematopoiesis
- M/E ratio decreased
Is flow cytometery and cytogenetics diagnostic for MDS?
NO! Important for providing prognostic risks and therapy but not diagnostic
Criteria for calling ringed sideroblasts in the erythrocyte line
At least 5 iron granules that circle at least 1/3 of the nucleus
What are the most common lab findings in MDS?
Macrocytic or normocytic anemia (w/ low retics)
Differentiating MDS from other conditions:
- MDS may present with ____ ____ RBCs but still have normal iron stores
Microcytic/hypochromic
Differentiating MDS from other conditions:
- MDS may present w/ megaloblastoid cellular development but still have ____ vitamin B12 and folate values
Normal
Most common MDSs
- Refractory Anemia w/ Excess Blasts (RAEB-1 and 2)
- Refractory Cytopenia w/ Multilineage Dysplasia
- Refractory Cytopenia w/ Unilineage Dysplasia
RAEB-1
- PB blasts
- BM blasts
- Auer rods present?
- % transform into AML
- Survival
- PB blasts: < 5%
- BM blasts: 5-9%
- Auer rods: NO
- 25% will transform to AML
- Survival: 16 months
RAEB-2
- PB blasts
- BM blasts
- Auer rods present?
- % transform into AML
- PB blasts: 5-19%
- BM blasts: 10-19%
- Auer rods: Possibly
- 33% will transform into AML
- Survival: 9 months
MDS w/ Isolated del(5q)
- What deletion?
- Predominately in what sex?
- What anemia is characteristic?
- Deletion of a 5q presumed tumor suppressor gene
- Predominately in women
- Macrocytic anemia is characteristic
What % of BM erythroid precursors are ringed sideroblasts in RARS (refractory anemia w/ ringed sideroblasts)?
More than 15%
How do you disitnguish myelodysplastic/myeloproliferative neoplasms from CML?
- BCR-ABL1 NEGATIVE
- Persistent monocytosis > 1.0 x 10^9/L
- Granulocytes < 10% of differential
One specific type of a myelodysplastic/myeloproliferative neoplasm
Juvenile Myelomonocytic Leukemia
How do you score the prognosis for a MDS?
International Prognostic Scoring System (IPSS)
International Prognostic Scoring System
- % BM blasts
- Karyotype
- # of cytopenias
< 2 is good; higher than 2 is bad
- More blasts is bad
- More aberrations is worse
- More cell lines shwoing cytopenai is worse
MDS
- Treatment
Lenalidomide and farnesyltransferase inhibitors
What prognostic score and what age must the patient be to receive the “cure” for an MDS?
- “cure” = stem cell transplant
- Score: > 2 IPSS
- Age: < 70
MDS etiology
- Somatic mutation
- Production of a pathologic clone
- Clonal expansion
- Possible further mutations
- Disruped apoptosis early in the disease could lead to increased apoptosis as disease progresses
Morphological features of dyserthropoiesis
- Oval macrocytes
- Hypochromatic microcytes
- Dimorphic RBC population
- RBC precursors w/ more than one nucleus
- Abnormal nuclear shapes (budding, bridging, hyperlobation, megaloblastic changes)
- Uneven cytoplasmic staining
- Ringed sideroblasts
- Vacuolization
- PAS positivity
Morphological features of dysmyelopoiesis
- Persistant basophilic cytoplasm
- Hypogranulation, agranulation, pseudo Chediak-Higashi granules, abnormally sized primary and secondary granules
- Pseudo Pelger-Huet, irregular hypersegmentation
- Uneven cytoplasmic staining
Morphological features of dysmegakaryopoiesis
- Giant platelets
- Abnormal granulation, hypogranulation or agranulation
- Micromegakaryocytes
- Large mononuclear megakaryocytes
- Bilobed or multiple small separated nuclei
Abnormal cellular function associated w/ dyserythropoiesis
- RBCs have shortened lifespan
- Erythroid precursors may have decreased sensitivity to EPO leading to anemia
Abnormal cellular function associated w/ dysmyelopoiesis
- Granulocytes have ↓ adhesion
- Granulocytes have deficient phagocytosis
- Granulocytes have ↓ chemotaxis
- Granulocytes have ↓ levels of MPO and alkaline phosphatase
Differentiating MDS from other conditions:
- MDS may present w/ myelodysplasia but have normal ____ levels
Copper
Differentiating MDS from other conditions:
- MDS may present w/ hypersegmented polys but still have normal ____ and ____ values
Vitamin B12; Folate
Abnormal cellular function associated w/ dysmegakaryopoiesis
Platelets may have increased bleeding depsite adequate platelet counts
RARS PB findings
- Anemia
- No blasts
RARS BM findings
- ≥15% of erythroid precurosrs are ringed sideroblasts
- Erythroid dysplasia only
- < 5% blasts
MDS associated w/ isolated del(5q) PB findings
- Anemia
- Usually normal or increased platelet count
- Nor or rare blasts (< 1%)
MDS associated w/ isolated del(5q) BM findings
- Normal to ↑ megakaryocytes w/ hypolobated nuclei
- < 5% blasts
- Isolated del(5q) cytogenic abnormality
- No Auer rods
MDSs are most common in which age group?
> 50 years old
What is a major indication of MDS in the PB and BM?
Dyspoiesis
According to the WHO classification of MDS, what percentage of blasts would constitute transformation into an acute leukemia?
20%
MDS most likely will transform into acute ____ leukemia
Myeloid
