Myelodysplastic Syndromes

Question 1

What general genetic changes lead to Myelodysplasia?

Answer 1

Loss of genetic material, maily chromosomal deletions (partial or whole) Thks is different from acute leukemias where it is mostly chromosomal translocations.

Epigenetic changes:

•Cancer related methylation related to aberrant gene expression

–Promoters

–CpG islands

•Other sites of methylation

–CpG shores

–Intergenic regions

–Distal regulatory regions

Defects in DNA synthesis in the background of adequate cell cycle checks.

Decreased or ineffective cell cycling.

Decreased cell counts, dysfunction of cells.

Question 2

Peripheral blood findings in Myelodysplasia (8)?

Answer 2

•Peripheral Blood Changes: Dyserythropoiesis

–Oval macrocytes (with normal B12 / folate)

–Hypochromic microcytes (with normal iron)

–Dimorphic RBC picture

–Poikilocytosis

–Basophilic stippling

–Howell-Jolly bodies

–Siderocytes

–Platelets with abnormal form / granulation

Question 3

What would you find in dysplastic bone marrow?

Answer 3

RBC precursors with multiple nuclei

RBC precursors with abnormal shapes

_—Lobes

_—-Buds

Nuclear fragments

Basophilic stippling

Heterogeneous staining of cytoplasm

Ringed sideroblasts

Megaloblastoid changes

Persistence of basophilia in otherwise mature WBCs

Primary granules may be larger than normal

Secondary granules may be absent

Question 4

Differentiate between B12/folate deficiency and dysplasia.

Answer 4

come back

Question 5

Refractory Anemia

Answer 5

•Anemia unresponsive to iron therapy

•Peripheral Blood

–Reticulocytopenia

–Oval macrocytes

–Blasts <1%

•Bone Marrow

–Iron stores are increased

–Granulocytic and megakaryocytic cells are normal

–<5% blasts

Question 6

Refractory anemia with ringed sideroblasts (RARS)

Answer 6

•Similar to RA except:

–>15% of BM cells are ringed sideroblasts

–To be a ringed sideroblast

• >5 granules must be present
• They must circle at least 1/3 of the nucleus

Question 7

Refractory anemia with excess blasts (RAEB)

Answer 7

•Peripheral Blood

^{–Oval macrocytes}

^{–Trilineage cytopenia}

^{–Dysmyelopoiesis / Dysmegakaryopoiesis}

^{•Hypogranular neutrophils}

^{•Pseudo-Pelger-Huet cells}

^{–Up to 19% blasts (>10% blasts = more aggressive disease}

•Bone Marrow

^{–Norm to hypercellular}

^{–Granulocytic and/or erythroid hyperplasia}

^{–5-20% blasts present}

Question 8

5q- Syndrome

Answer 8

• Deletion of the q arm of chromosome 5
• Mostly women over 50
• Characterized by

_{–Refractory macrocytic anemia}

_{–Thrombocytosis}

_{–Hypolobulated megakaryocytes}

_{–Erythroid hypoplasia}

•Respond to lenalidomide (66%)

Question 9

Chronic Myelomonocytic Leukemia (technically a MDS / MPD)

Answer 9

•Peripheral blood: Like RA

–Oval macrocytes

–Reticulocytopenia

–Thrombocytopenia (+/-)

–WBC count high

–Absolute monocytosis

•Bone Marrow

–Granulocytic hyperplasia with dysmegakaryopoiesis

–5-20% of cells are blasts

Question 10

What are the treatments for myelodysplastic syndrome? Advantages? Disadvantages?

Answer 10

Mostly palliative:

–Transfusions

• RBC
• Platelets

–Colony Stimulating Factor

To cure – replace hematopoetic progenitors

–Bone marrow transplant

–Cord blood

–Low intensity transplant

•Graft v. leukemia

Complications

–Graft v. host disease

–Rejection of graft

Question 11

Describe bone marrow and peripheral blood findings in the myelodysplastic syndrome: RA, and RARS

Answer 11

Question 12

Describe bone marrow and peripheral blood findings in the myelodysplastic syndrome: RAEB, 5-q syndrome and myelomonocytic leukemia.

Answer 12