Myelodysplastic Syndromes (MDSs)

Question 1

Group of acquired clonal hematologic disorder that affect maturation of erythroid, myeloid, and/or megakaryocytic lines
- PROGRESSIVE PB CYTOPENIAS (MAY EVENTUALLY PROGRESS TO AML)

Answer 1

Myelodysplastic Syndromes (MDSs)

Question 2

Mechanism of MDSs

Answer 2

Hypomethylation of DNA followed by hypermethylation of DNA

Question 3

Which MDS mechanism leads to reduced transcription leading to cytopenias?

Answer 3

Hypomethylation of DNA

Question 4

Which MDS mechanism leads to enhanced transcription leading to an acute leukemia (usually AML)

Answer 4

Hypermethylation of DNA

Question 5

MDS PB findings

Answer 5

• Cytopenias
• Anemia (N/N or macrocytic anemia)
• Dysplasia

Question 6

MDS BM findings

Answer 6

• Hypercellular
• Dysplasia
• Ineffective hematopoiesis
• M/E ratio decreased

Question 7

Is flow cytometery and cytogenetics diagnostic for MDS?

Answer 7

NO! Important for providing prognostic risks and therapy but not diagnostic

Question 8

Criteria for calling ringed sideroblasts in the erythrocyte line

Answer 8

At least 5 iron granules that circle at least 1/3 of the nucleus

Question 9

What are the most common lab findings in MDS?

Answer 9

Macrocytic or normocytic anemia (w/ low retics)

Question 10

Differentiating MDS from other conditions:

- MDS may present with ____ ____ RBCs but still have normal iron stores

Answer 10

Microcytic/hypochromic

Question 11

Differentiating MDS from other conditions:

- MDS may present w/ megaloblastoid cellular development but still have ____ vitamin B12 and folate values

Answer 11

Normal

Question 12

Most common MDSs

Answer 12

• Refractory Anemia w/ Excess Blasts (RAEB-1 and 2)
• Refractory Cytopenia w/ Multilineage Dysplasia
• Refractory Cytopenia w/ Unilineage Dysplasia

Question 13

RAEB-1

• PB blasts
• BM blasts
• Auer rods present?
• % transform into AML
• Survival

Answer 13

• PB blasts: < 5%
• BM blasts: 5-9%
• Auer rods: NO
• 25% will transform to AML
• Survival: 16 months

Question 14

RAEB-2

• PB blasts
• BM blasts
• Auer rods present?
• % transform into AML

Answer 14

• PB blasts: 5-19%
• BM blasts: 10-19%
• Auer rods: Possibly
• 33% will transform into AML
• Survival: 9 months

Question 15

MDS w/ Isolated del(5q)

• What deletion?
• Predominately in what sex?
• What anemia is characteristic?

Answer 15

• Deletion of a 5q presumed tumor suppressor gene
• Predominately in women
• Macrocytic anemia is characteristic

Question 16

What % of BM erythroid precursors are ringed sideroblasts in RARS (refractory anemia w/ ringed sideroblasts)?

Answer 16

More than 15%

Question 17

How do you disitnguish myelodysplastic/myeloproliferative neoplasms from CML?

Answer 17

• BCR-ABL1 NEGATIVE
• Persistent monocytosis > 1.0 x 10^9/L
• Granulocytes < 10% of differential

Question 18

One specific type of a myelodysplastic/myeloproliferative neoplasm

Answer 18

Juvenile Myelomonocytic Leukemia

Question 19

How do you score the prognosis for a MDS?

Answer 19

International Prognostic Scoring System (IPSS)

Question 20

International Prognostic Scoring System

• % BM blasts
• Karyotype
• # of cytopenias

Answer 20

< 2 is good; higher than 2 is bad

• More blasts is bad
• More aberrations is worse
• More cell lines shwoing cytopenai is worse

Question 21

MDS

- Treatment

Answer 21

Lenalidomide and farnesyltransferase inhibitors

Question 22

What prognostic score and what age must the patient be to receive the “cure” for an MDS?

Answer 22

• “cure” = stem cell transplant
• Score: > 2 IPSS
• Age: < 70

Question 23

MDS etiology

Answer 23

• 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

Question 24

Morphological features of dyserthropoiesis

Answer 24

• 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

Question 25

Morphological features of dysmyelopoiesis

Answer 25

- Persistant basophilic cytoplasm - Hypogranulation, agranulation, pseudo Chediak-Higashi granules, abnormally sized primary and secondary granules - Pseudo Pelger-Huet, irregular hypersegmentation - Uneven cytoplasmic staining

Question 26

Morphological features of dysmegakaryopoiesis

Answer 26

- Giant platelets - Abnormal granulation, hypogranulation or agranulation - Micromegakaryocytes - Large mononuclear megakaryocytes - Bilobed or multiple small separated nuclei

Question 27

Abnormal cellular function associated w/ dyserythropoiesis

Answer 27

- RBCs have shortened lifespan | - Erythroid precursors may have decreased sensitivity to EPO leading to anemia

Question 28

Abnormal cellular function associated w/ dysmyelopoiesis

Answer 28

- Granulocytes have ↓ adhesion - Granulocytes have deficient phagocytosis - Granulocytes have ↓ chemotaxis - Granulocytes have ↓ levels of MPO and alkaline phosphatase

Question 29

Differentiating MDS from other conditions: | - MDS may present w/ myelodysplasia but have normal ____ levels

Answer 29

Copper

Question 30

Differentiating MDS from other conditions: | - MDS may present w/ hypersegmented polys but still have normal ____ and ____ values

Answer 30

Vitamin B12; Folate

Question 31

Abnormal cellular function associated w/ dysmegakaryopoiesis

Answer 31

Platelets may have increased bleeding depsite adequate platelet counts

Question 32

RARS PB findings

Answer 32

- Anemia | - No blasts

Question 33

RARS BM findings

Answer 33

- ≥15% of erythroid precurosrs are ringed sideroblasts - Erythroid dysplasia only - < 5% blasts

Question 34

MDS associated w/ isolated del(5q) PB findings

Answer 34

- Anemia - Usually normal or increased platelet count - Nor or rare blasts (< 1%)

Question 35

MDS associated w/ isolated del(5q) BM findings

Answer 35

- Normal to ↑ megakaryocytes w/ hypolobated nuclei - < 5% blasts - Isolated del(5q) cytogenic abnormality - No Auer rods

Question 36

MDSs are most common in which age group?

Answer 36

> 50 years old

Question 37

What is a major indication of MDS in the PB and BM?

Answer 37

Dyspoiesis

Question 38

According to the WHO classification of MDS, what percentage of blasts would constitute transformation into an acute leukemia?

Answer 38

20%

Question 39

MDS most likely will transform into acute ____ leukemia

Answer 39

Myeloid