Week 2: Heme Cx

Question 1

what is acute leukemia?

Answer 1

malignant white cells in bone marrow and blood

Question 2

in terms of bone marrow, describe acute leukemia

Answer 2

bm failure

anemia, neurtopenia, thrombocytopenia

Question 3

can acute leukemia metastasize?

Answer 3

yes, to the liver, spleen, lymph nodes, brains, meninges, skin,

Question 4

what is the classification system for acute leukemia? What are the scales for AML and ALL?

Answer 4

FAB (French American British)
M 0-7
L 1-3

Question 5

what kind of acute leukemia is most common in kids? in adults? in the general population?

Answer 5

kids - ALL
adults - AML
overall - AML (bc of number of adults)

Question 6

what is the age range in kids for ALL?

Answer 6

3-7 YO

40 YO

Question 7

what is the difference between primary and secondary AML?

Answer 7

primary: de novo
secondary: from myelodysplastic syndromes, etc.

Question 8

the cause/origin of most acute leukemia is _____

Answer 8

idiopathic

Question 9

what are some associated genetic diseases with acute leukemia?

Answer 9

Downs
fragile chromosome (Fanconi’s Anemia)
aplastic anemia
PNH

Question 10

what is the mechanism for the pathogenesis (starting point) of acute leukemia?

Answer 10

starts in a hematopoietic stem cell or early progenitor cell

Question 11

what are the three traits of acute leukemia pathogenesis? what do these things do overall?

Answer 11

1. inc prolif rate
2. dec apop
3. block cell diff
   overall: accumulate blast cells **

Question 12

number-wise, how do you classify acute leukemia?

Answer 12

> 20% blasts

<20% blasts with AL-associated cyto, molecular genetic abnormalities

Question 13

how do you determine AML v. ALL?

Answer 13

• immunophenotyping

- Auer Rods

Question 14

which AL has Auer Rods?

Answer 14

AML

Question 15

what is immunophenotyping?

Answer 15

read Ag pattern expression

Question 16

what are the Myeloid Ag?

Answer 16

MPI
CD33
CD13
HLA-DLR
**

Question 17

what are the Lymphoid Ag?

Answer 17

TdT
CD10
CD19
CD20
**

Question 18

list the FAB Classification of AML

Answer 18

M0 undiff
M1 without maturation
M2 with granulocytic maturation 
M3 acute promyelocytic (assoc with Auer Rods?)
M4 granulocytic and momocytic maturation 
M5 (a) monoblastic or (b) monocytic 
M6 erythroleukemia
M7 megakaryocytic

Question 19

list the FAB Classification of ALL

Answer 19

L1 blast cells small, uniform nuc:cyto ratio
L2 blast cells larger, hetergenous, lower nuc:cyto ration
L3 vaculoated blasts, basophilic cytoplasm

Question 20

t(15;17)

Answer 20

PML-RARalpha

M3

Question 21

t(8;21)

Answer 21

ETO/AML1

M1

Question 22

ETO/AML1 is a _____

Answer 22

CBF (core binding factor)

Question 23

PML-RARalpha does what to encourage leukemia? by what mechanism? what stops action?

Answer 23

represses differentiation genes :: reroutes into leuk stem cells

all-trans retinoic acid (vit A) + arsenic (break up protein dimer)

Question 24

what are three “good prognosis” AMLs?

Answer 24

t(15;17)
t(8;21)
inv(16)

Question 25

PML-RARalpha creates AL by what mechanism?

Answer 25

dimer protein binds to histones and DNA histone methyltransferase DNA methyltransferase

Question 26

when you look at a fusion protein with FISH, what will the signal look like?

Answer 26

yellow, if the 2 genes are tagged red and green :: a combination of the two

Question 27

who responds better to high dose chemo in AML, children or olds?

Answer 27

children

Question 28

what can we give olds with AML that is not cytotoxic?

Answer 28

Azacitidine doesn't cure but increases life span

Question 29

three stages of Tx for AML

Answer 29

1. remission induction 2. post-remission/ consolidation 3. maintenance (in some pts)

Question 30

describe AML remission induction

Answer 30

- 1-2 courses of intense Tx - want "complete response" i.e., - absence of detectable leuk cells

Question 31

describe AML post-remission Tx

Answer 31

- consolidation therapy - 3-4 intense short-course Tx - further reduce the subclinical body burden

Question 32

describe AML maintenance Tx

Answer 32

- only in some pts - mo-yrs of less intense Tx to further prevent occurrence (OR) - allogenic bone marrow transplant

Question 33

what information do we need to asses risk and determine the therapy plan (how intense the chemo needs to be) for AL?

Answer 33

cytogenetics

Question 34

what do we use for molecular assessment?

Answer 34

PCR

Question 35

what are the "poor prognosis" ALLs? what is the genetic mechanism? what pop are the prominent in?

Answer 35

MLL-AF4 BCR-ABL translocation kids + adults [think: MiLLie is mean, BCR sounds like BRCA...both bad]

Question 36

what are the "good prognosis" ALLs? what is the genetic mechanism? what pop are the prominent in?

Answer 36

E2A-PBX TEL-AML hyperdiploidy kids; rare in adults [note: TEL-AML is still an ALL and not what its name might imply // think: "elizabeth 2 anne" has to "TELl AMLee" about the "extreme PB&J"...bc extreme sandwiches are good]

Question 37

what is the mechanism for the "poor prognosis" ALLs?

Answer 37

translocation

Question 38

what is the aspect to adult leukemia that might make it different from kids?

Answer 38

possible genetic feature

Question 39

what med can be used to manage secondary effects of ALL? what is the secondary symptom?

Answer 39

- Allopurinol - manage hyperuricemia (inc uric acid) that comes with tumor breakdown *** - also CNS prophylaxis

Question 40

describe ALL induction Tx

Answer 40

VCR L-Asp DEX or PRED +/- Daunorubicin

Question 41

describe ALL consolidation Tx

Answer 41

``` Daunorubicin HD Ara-C VCR Etoposide Thioguanine or 6-Mercap Cyclophosphamide L-ASP ```

Question 42

describe ALL maintenance Tx

Answer 42

6-MP MTX PRED

Question 43

describe the CNS prophylaxis for ALL

Answer 43

intrathecal MTX or ARA-C

Question 44

what molecular abnormality gives a poor AML prognosis?

Answer 44

FLT3-IDT