AML

Question 1

AML therapeutic backbone

Answer 1

daunorubicin and cytarabine
gemtuzumab
TKI if FLT3+

Question 2

AML risk stratification

Answer 2

Favourable
- CEBPA, NPM1, inv(16), t(8;21)
- AMPL = t(15;17)
- T21<4yo

Unfavourable
- cytogenetics: KMT2A, -7, -5, del(5q), FLT3-ITD allelic ratio >0.1,
- RAM phenotype (GLIS2): bright CD56, -CD45, -CD38, -HLA-DR
- therapy- or MDS-related AML
- Primary induction failure
- older age
- Hispanic/Black ethnicity
- higher WBC at diagnosis

Question 3

JMML criteria

Answer 3

Class 1 (all 4 required)
- monocyte >= 1x10^9
- blast<20%
- splenomegaly
- no Ph or KMT2A

Class 2 (any one)
- PTPN11, KRAS, NRAS
- NF1
- CBL germline mutation

Class 3 (2+ of)
- increased HbF
- myeloid/erythroid precursors
- GMCSF hypersensitivity
- thrombocytopenia w hypercellular marrow and decreased megakaryocytes

Question 4

TAM mutation

Answer 4

GATA1

Question 5

TAM risk stratification

Answer 5

HR: life-threatening symptoms; hepatomegaly, liver/renal dysfunction, DIC, effusions, WBC>100
IR: hepatomegaly
LR: none of above

Question 6

ATRA syndrome - presentation and tx

Answer 6

fever, edema, pulmonary infiltrates, effusions, resp distress, hypotension, renal/liver dysfunction

Tx: dex 3+d until resolution; hold ATRA

Question 7

Infant blast DDx

Answer 7

infant ALL, AML
TAM
JMML
leukemoid reaction

Question 8

AML IT

Answer 8

weekly TIT until cleared then 1/course

Question 9

AML HSCT indications

Answer 9

Induction failure
HR
IR
relapse
JMML

Question 10

t-AML causes and cytogenetics

Answer 10

topo II inhibitors (etop > anthracyclines): KMT2Ar

Alkylators (Cy, cisplatin): -5, -7, del5q, del7q

Question 11

AML twin concordance

Answer 11

Dx <1yo, near 100%
Dx 1-6yo, 10-20% concordance
Dx y+yo, minimal increased risk

Question 12

AML etiology (inherited, acquired)

Answer 12

Inherited:
- T21, Noonan (JMML), bloom, IBMFS
- germline mutations: CEBPA, DDX41, TP53, RUNX1, ANKRD26, ETV6, GATA2

Acquired: ionizing radiation, benzene, pesticide, topo II inhibitors (etop, anthra), alkylators (Cy, cisplat), PNH, MDS, SAA

Question 13

TAM risk of AML

Answer 13

10-30% risk if resolution

Question 14

T21 AML age risk stratification

Answer 14

<4yo more favourable
>4yo similar to non-T21

Question 15

Relapse AML therapy

Answer 15

FLAG-GO: fludarabine, HD cytarabine, GCSF, gemtuzimab
HSCT

Question 16

AML Tx by risk stratification

Answer 16

HR: 3 courses then HSCT
LR or HR w/o donor: 5 courses
LR-fav (fav cyto and EOI1 MRD neg): 4 courses

Question 17

AML Px

Answer 17

EFS 50% OS 70%
LR: DFS 70% OS 88%
HR: OS 50%

Question 18

T21 risk of ALL/AML

Answer 18

<4yo: 40x ALL, 150x AML; cumulative risk 2%
5-30yo: decreases to 10-20x

Question 19

AML specific cell surface markers

Answer 19

CD 11b, 13, 14, 15, 33, 36 ,41, 42, 61, 64, 117, 163
MPO
HLA-DR (not APL or RAM)

Question 20

RAM phenotype

Answer 20

CBFA2T3-GLIS2
Bright CD 56
dim-neg CD 45, 37
neg HLA-DR

Question 21

AML and ALL MRD

Answer 21

ALL: 0.01%
AML: 0.1%

Question 22

APML risk stratification

Answer 22

SR: WBC<10
HR: WBC 10+

Question 23

MPAL Tx strategy

Answer 23

included on ALL trials. ALL therapy > AML therapy

Question 24

JMML RF

Answer 24

Noonan (15% of cases)
NF1 (10% of cases)

Question 25

JMML presentation

Answer 25

HSM, LN, rash
pallor, fever, bleeding, infection