Exam 3 - Acute Leukemias, Myeloproliferative Disorders, and MDS

Question 1

TdT

Answer 1

marker of lymphoblasts

not expressed by mature lymphocytes or myeloblasts

Question 2

CD34

Answer 2

immature marker of blasts

could be lymphoblasts or myeloblasts

Question 3

Acute lymphoblastic leukemia (ALL)

Answer 3

replacement of marow by lymphoblasts

Question 4

Types of ALL

Answer 4

B-lymphoblastic ALL (80%) - children

T-lymphoblastic ALL (20%) - older

Question 5

B-lymphoblastic ALL

Answer 5

CD34, TdT

CD19, CD22 (No CD20, mature)

Question 6

T-lymphoblastic ALL

Answer 6

Large mediastinal mass
More likely high WBC
CD34, TdT
CD3, CD7, CD4, CD8, CD99

Question 7

Cytogenetics B-ALL

Answer 7

t(9;22) Philadelphia - worst (adult)
11q23 (MLL) - poor (infant, congenital)
t(12;21) ETV6-RUNX1 - favorable (child)

Question 8

5 worse prognostic factors for ALL

Answer 8

Increased age
Increased WBC
Slow response to therapy
less hyperdiploidy
T-ALL (compared to B-ALL)

Question 9

Acute myeloid leukemia (AML)
Smear for myelo
Markers for myelo
Markers for other two cell lines

Answer 9

>20% myeloblasts in marrow or blood (unless cytogenetic findings)
Myeloblasts (auer rods)
CD34
CD117, MPO - myeloid markers
CD64, CD14
CD41, CD61

Question 10

CD64, CD14

Answer 10

Monocytic lines

Question 11

CD41, CD61

Answer 11

Megakaryocytic lines

Question 12

Cytogenetics AML

Answer 12

t(8;21) RUNX1-RUNX1T1: alpha-CBF - good
Inv(16) or t(16;16) CBFB-MYH11: ß-CBF - good
t(15;17) PML-RARA
t(1;22): megakaryoblastic - good
11q23 (MLL): monocyctic - poor

Question 13

t(15;17) PML-RARA in AML

Answer 13

Acute promyelocytic leukemia
Tx with retinoic acid
Check for DIC

Question 14

Therapy related AML

Answer 14

Loss of 5 or 7 (alkylating agents or radiation)
Rearrange MLL 11q23 (topoisomerase II inhibitors)
Very poor prognosis

Question 15

AML Not Otherwise Specified

Answer 15

FLT3 ITD (negative prognostic factor)
NPM1 (positive prognostic factor)
CEBPA (positive prognostic factor)

Question 16

Myelodysplastic Syndrome

Answer 16

Ineffective hematopoiesis (increased ineffective cells)
Increased risk transformation to AML
Replacement of marrow with myeloid lines (to extent)
Primary or secondary

Question 17

MDS: Changes in ___% but less than ___% of which myeloid cell lines and what are the characteristic findings?

Answer 17

10%, 20% (=AML)
Dyserythropoiesis (ring sideroblasts)
Dysgranulopoiesis (bilobed nuc, pseudo-Pelger-Heut cells)
Dysmegakaryopoiesis (hypo/non-lobed nuc)

Question 18

Cytogenetic Findings of MDS

Answer 18

Deletions 5 or 7 or (5q)

Trisomy 8

Question 19

Secondary MDS

Answer 19

morphologic evidence without cytogenetics or increased blasts
Vitamin def
Toxin exposure
Drug exposure
Viral infection

Question 20

Low grade MDS

Question 21

High grade MDS

Answer 21

>5% marrow, >2% blood myeloblasts (>20%=AML)
Refractory anemia with excess blasts 1
5-9%, 2-4%
Refractory anemia with excess blasts 2
10-19%, 5-19%
Dismal prognosis

Question 22

Myeloproliferative Neoplasms

4 cell lines

Answer 22

Non-dysplastic proliferation of 1 or more myeloid lines

Granulo, erythoid, megakary, mast

Question 23

Characteristics of MPN

Answer 23

Hypercellular marrow
Spleno/hepatomegaly
Insidious onset
Progress to AML, ALL, MDS, marrow fibrosis

Question 24

Classifications of MPN

Answer 24

Chronic myelogenous leukemia (CML)
Polycythemia vera (PV)
Primary myelofibrosis (PMF)
Essential thrombocythemia (ET)

Question 25

CML clinical findings and bone marrow biopsy findings

Answer 25

Leukocytosis (neutrophilia) Increased basophils Increased platelets Bone marrow biopsy: hypercellular marrow, small megakaryocytes with round, non-lobated nuclei, no dysplasia

Question 26

CML genetics and treatment

Answer 26

BCR-ABL1 | Tx: protein tyrosine kinase inhibitors

Question 27

PV clinical findings and unique symptoms

Answer 27

Erythrocytosis Plethora, pruritus, paresthesias Rare to progress to AML End with fibrosis

Question 28

PV genetics and secondary PV

Answer 28

``` JAK2 (V617F) activation W/out mutation = secondary Smokers (carboxyhemoglobin) Chronic hypoxia Hb disorders ```

Question 29

Phases of PV

Answer 29

``` Polycythemic phase (high counts) Spent phase (post PV, fibrosis of bone marrow) ```

Question 30

Major complication of PV

Answer 30

Venous or arterial thrombosis | Especially: mesenteric, portal or splenic vein

Question 31

PMF characteristics

Answer 31

PV w/out erythrocytosis (50% JAK2 mutation) Instead: granulo/megakaryo line No JAK2 = MPL or CALR mutation Progress to fibrotic stage (organ enlargement) Rare to progress to AML

Question 32

ET characteristics

Answer 32

``` 50% JAK2 No JAK2 = MPL or CALR mutation No granulo, megkaryocytes are larger Risk for transient ischemic attacks NO SPLENOMEGALY ```