Myelodysplastic Syndrome & Myeloproliferative Neoplasms

Question 1

List the 2 main features that characterize myelodysplastic syndrome (MDS).

Answer 1

1. Ineffective Hematopoesis

2. Increased risk of transformation to acute leukemia

Question 2

List the 2 clinical scenarios of MDS.

Answer 2

1. Primary, idiopathic MDS- Elderly (median age 70), 3-5/100,000 per year
2. Secondary, therapy related MDS- Diagonses 2-8 years post therapy (DNA alkylating or ionizing radiation), complex karyoptype (part/full del. ch 5/7)

Question 3

List 3 different Signs of MDS that can lead to a diagnosis

Answer 3

1. Persistent peripheral cytopenia in 1+ lineages
2. If only one lineage, it is almost always persistent anemia
3. Persistent cytopenia in 2+ lineages in patients of advanced age

Question 4

List 3 different types of tests that could be performed to make a diagnosis of MDS.

Answer 4

1. morphological evidence of dysplasia (Look at a smear, or karyotype)
2. Increased myeloblasts (but less than 20% of blood/marrow)
3. Presence of clonal cytogenetic abnormalities

Question 5

List 4 possible causes of secondary myelodysplasia that might mimic MDS.

Answer 5

1. Vitamin Deficiency (B12, folate)
2. Toxin Exposure (Heavy metals)
3. Exposure to certain drugs
4. Viral infections

Question 6

Pelgeroid Cells (Image)

Answer 6

Dysplastic neutrophils with two lobes

Question 7

Low Grade MDS

Answer 7

Myeloblasts are not increased in frequency (<2% in blood)

Question 8

High Grade MDS

Answer 8

Myeloblasts are increased in frequency, but less than 20% (myeloblasts account for 5-19% of marrow cells, and/or 3-19% of blood cells)

Question 9

Refractory Cytopenia with Unilineage Dysplasia, RCUD

Answer 9

Low grade

Relatively good prognosis

Question 10

Refractory anemia with Excess Blasts 1- RAEB-1

Answer 10

High Grade

Relatively Dismal prognosis
5-9 in marrow, 2-4 in blood

Question 11

Myeloproliferative Neoplasms (MPNs)

Answer 11

Arise from transformed hematopeotic cells (Like MDS)

Still effective hematopeosis however

Younger patients than MDS

Marrow growing too much

Question 12

List 2 reasons for the frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs.

Answer 12

1. Too many cells, so they’re sequestered in the two organs

2. Transition to extramedullary production of blood cells with marrow fibrosis

Question 13

List 3 possible negative end points for MPNs.

Answer 13

1. Excessive marrow fibrosis (marrow aging and scarred)
2. Transform to acute leukemia
3. The two megaly’s

Question 14

Refractory Cytopenia with Multilineage Dysplasia (RCMD)

Answer 14

Low Grade
Dysplasia in 2 or more lineages
Worse prognosis than RCUD
10% transform to AML

Question 15

Chronic Myelogenous Leukemia (CML)

Answer 15

Increased WBC (12,000 to 1,000,000)
Neutrophilic leukocytosis

Increased basophils and often platelets

If untreated, goes to blast phase (basically acute leukemia)

Question 16

Polycythemia Vera (PV)

Answer 16

Increased in RBC mass
Sometimes increased neutro’s and plts

Transforms to spent phase (fibrotic marrow, bone marrow failure)

Question 17

Primary Myelofibrosis (PMF)

Answer 17

Granulocytic and megakaryocytic hyperplasia

Leukoerythrobastosis- more immature cells than usual (both RBC and WBC)

Teardrops in the bloodsmear because squeezed out marrow

The two megaly’s due to extramedullary hematopoesis

Question 18

Essential Thrombocythemia (ET)

Answer 18

Just increased megakaryocytes -> increased plts

Question 19

Refractory Anemia with Excess Blasts-2 (RAEB-2)

Answer 19

High grade
“Very dismal”
10-19% blasts in marrow, and/or 5-19% blasts in blood

Question 20

Explain why there is a need for a second and third generation of protein tyrosine kinase inhibitors (PTKIs).

Answer 20

Cancer has developed resistance through mutations involved imatinib binding sites

Question 21

List 3 sites where thrombosis should always make one consider the possibility of PV.

Answer 21

1. ) Mesenteric Vein
2. ) Hepatic Portal Vein
3. ) Splenic Vein

Question 22

The most common method of death attributable to disease in polycythemia vera (PV) patients

Answer 22

Thrombotic events

Question 23

Describe findings that might be seen in a peripheral blood smear of a patient with leukoerythroblastosis and how these findings relate to patients with marrow fibrosis.

Answer 23

A lot of immature WBCs and RBCs in peripheral blood because the firbrosis is forcing the blasts out of the marrow sooner

Dacryocytes

Question 24

Chronic Myelogenous Leukemia (CML)

Cytogenic Finding

Answer 24

BCR-ABL gene fusion t(9;22), philadelphia chr. fusion protein

Question 25

Chronic Myelogenous Leukemia (CML)

Marrow Finding

Answer 25

Hypercellular bone marrow and granulocytic hyperplasia

Question 26

Polycythemia Vera (PV)

Cytogenic Finding

Answer 26

Point Mutation of JAK2, a cell signalling pathway protein

Question 27

Polycythemia Vera (PV)

Marrow Finding

Answer 27

Marrow is hypercellular, with bizarre megakaryocytes

Question 28

Primary Myelofibrosis (PMF)

Cytogenic Findings

Answer 28

Jak2 mutation in 50%, other 50% have MPL or CALR mutation

Question 29

Primary Myelofibrosis (PMF)

Marrow Findings

Answer 29

Hypercellular marrow

Large, bizarre megakaryocytes

Question 30

Essential Thrombocythemia (ET)

Cytogenic Findings

Answer 30

Jak2 mutation 50% of time, otherwise MPL or CALR

Question 31

Essential Thrombocythemia (ET)

Marrow Findings

Answer 31

It lacks the marrow granulocytic hyperplasia often seen in PMF, and the atypical megakaryocytes in ET are even larger than those in PMF