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Erez's HEM TEST notes 2024 > AML facts > Flashcards

AML facts Flashcards

1
Q

AML with myelodysplasia-related
gene mutations

A

ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2

BREASSSUZ- BCOR, RUNX1, EZH2, ASXL1, SRSF2, SF3B1, STAG2, U2AF1, ZRSR2

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2
Q

Hierarchy of AML classification

A

Recurrent mutational abnormalities
# p53
# myelodysplasia-related gene mutation
# myelodysplasia-related cytogenetic abnormalities
# NOS

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3
Q

Qualifiers for AML classification (ICC)

A

Therapy related
Prior MDS, MDS/MPN
Germline disposition

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4
Q

AML with myelodysplasia-related cytogenetic abnormalities

A

Complex karyotype
5
7
12
17
20

7+5=12
12+5=17
5+5+5+5=20

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5
Q

Therapy related AML after alkylating agents/radiation

A

5-7 years latency
Preceded by MDS
Complex karyotype

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6
Q

Therapy related AML after topoisomerase Tx

A

Etoposide/Anthracyclines
1-3 years latency
Antecedent MDS is rare
MLL rearrangement

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7
Q

Important germline mutations in AML and their presetation

A

DDX41- older age of presentation - good prognosis
ANKRD26, ETV6, and RUNX1- Platelet defects
GATA2- immunodeficiency
Shwachman Diamond syndrome - pancreatic insufficiency+ skeletal dysplasia
Fanconi anemia - facial dysmorphism, squamous cell carcinomas, liver tumors
Dyskeratosis congenita with pulmonary fibrosis, liver cirrhosis,
and vascular anomalies

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8
Q

Precurser markers in AML

A

CD34, CD117, HLA-DR

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9
Q

Myeloid markers in AML

A

Cytoplasmic MPO, CD33, CD13

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10
Q

Monocytic markers in AML

A

CD14, CD36, CD64, lysozyme
CD4, CD38,
CD11c

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11
Q

Megakaryocytic markers in AML

A

CD41 (glycoprotein IIb/IIIa), CD61
(glycoprotein IIIa), CD36

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12
Q

MPAL immuphenotype

A

MPO/monocytic
+ CD3
or CD19+CD79a/CD22/CD10

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12
Q

Erythroid markers in AML

A

CD235a (glycophorin A), CD71,
CD36

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13
Q

Favorable risk AML

A

inv16 (core binding factor)
t8:21 (RUNX1)
NPM1
bZIP in frame CEPBA

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14
Q

Intermediate risk AML

A

FLT3
t(9:11) MLL:KMT2A
NOS

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15
Q

Poor risk AML

A

T(6:9) -Basophilia
inv3- EVI1
t(9:22)
MDS related mutations (BREASSSUZ)/cytogentic abnormalities (5, 7, (8), 12, 17, 20)
p53

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16
Q

Timing of response assessment in AML

A

2 cycles of intensive therapy
180 days of VV

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17
Q

CPX-351 induction in AML

A

High risk or post MDS (Hx or cytogenetic)
pts 60-75
Less mucositis and TRM
Longer time to neut recovery
Better 5 year OS (18% vs 10%)
Higher ORR

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18
Q

IDH1 i combination in ND AML

A

AGILE
HMA +- Ivosidenib
OS benefit
24 months median OS
Differentiation syndrome 14%

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19
Q

Principal of tranplant decision in AML (risk/benefit)

A

When relapse rates are >35-40%

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20
Q

MAC vs RIC in AML

A

If MRD is positive before transplant- Improved OS with MAC
In young fit pts MAC is better than RIC

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21
Q

Number of chemo cycles prior to transplant in AML

A

No advantage for >2 cycles

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22
Q

VV maintenance post transplant in AML

A

Still in research
Seems safe and effective
5 days pf AZA (35mg/m2) with 14 days ven 400 mg

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23
Q

CHIP mutations in AML

A

DTA
DNMT3A, TET2, ASXL1

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24
Sorafenib maintenance after allo
SORMAIN trial limitation- no midostaurin in induction Improves OS
25
GATA2-related MDS
Monosomy 7 Young age Hx of immunodeficiency
26
ELN 2024 classification in AML pts on VV
P53- poor RAS FLT3- int NPM1 IDH DDX41- favorable
27
When to consider LP in CR1 of AML
Monocytic differentiation MPAL WBC >40 at diagnosis Extramedullary disease FLT3 mutations
28
RUNX1 mutated AML
Older age, male gender, and secondary AML Presents with thrombocytopenia
29
Inv16 gene
CBFB-MYH11
30
t(8:21)
RUNX1-RUNX1LT1
31
Cutoff of 20% for AML with genetic alterations
BCR:ABL1 CBPA
32
AML with defining genetic abnormalitis (not requiring blast threshold)
PML:RARA Core binding factor NPM1 KMT2A MECOM DEK:NUP214 RBM15:MRTFA NUP98
33
AML inv16 morphology
Eosinophilic granules in blasts
34
Down syndrome associated AML
GATA1 mutated Seen only in Down syndrome Megakayoblastic
35
APL thresholds for PLT/Cryo
PLT 30-50 Fib 150-200
36
Tx of differentiation syndrome
Dexa 10 mg 2/d for 3 days after dyspnea resolves
37
Tx of APL in CR2
Auto transplant
38
Type I FLT3 inhibitors
Midostaurin Giltretinib (Active+non active conformation FLT3, TKD+ITD)
39
Type II FLT3 inhibitors
Quizartinib Sorafinib (Active FLT3, ITD)
40
Quizartinib in AML
QUANTUM FIRST pts 18-75 OS advantage in pts <60
41
Maintenance gilt after ASCT in AML
MORPHO trial Negative trial (0.051) But OS advantage in MRD+ pts
42
Number of somatic mutations on de novo AML
13 5 of them driver mutations
43
ATRX mutations im AML
Thalassemia like phenotype
44
AML biology def
Clonal somatic mutations with proliferation and maturation arrest Acquisition over time
45
Calculator for CCUS risk
CHRS
46
CEBPA mutation
In frame bZIP mutation Germline CEBPA 100% penetrance. Good prognosis
47
DDX41 germline mutation
Older age Good risk
48
GO SE
Prolonged thrombocytopenia VOD
49
MRD change that defines progression in AML
1 log increase
50
Onureg
QUAZAR Oral azacitidine High risk pts not going to tranplant Improves OS
51
Management of MRD failure NPM1 AML
Preemptive therapy with ASCT with or without bridging
52
Prognostic groups for AML pts Tx with VV
Poor- p53 Intermedate- KRAS, NRAS, FLT3-ITD Favorable- NPM1, IDH1, IDH2, DDX41
53
Is single agent venetoclx maintenance effective after MRD neg on VV
No High degree (50%) of relapse Not salvageable with reinitiating of vidaza
54
Daunorubicin dosage in induction
90 better than 45 60 as effective as 90
55
AML presenting with extreme leukocytosis
FLT3 RAS
56
AML with t(6;9) blast count threshold
10% Usually prominent basophilia WHO does not require blast threshold
57
APL with other RARA rearrangement blast count threshold
10%
58
Management of prolonged (>42 days) cytpenia in VV Tx of AML
Shorten venetoclax duration Reduce AZA dosage Increase inter-cycle interval Administer GCSF during expected nadir
59
CBF MRD in AML that is exceptable for FU only
1%
60
NPM1 MRD in AML that is exceptable for FU only
2%
61
D14 in AML
Not as significant as ELN risk score
62
Tx of low positive NPM1 AML with FLT3
Allo Consider Low intensity Tx to erase MRD (VALDAC)
63
Tx of low positive NPM1 AML without FLT3
FU
64
Oral AZA in high risk AML pts not receiveing allo
OS advantage Mainly effective in MRD positive pts
65
MRD testing in AML (PB vs BM)
BM at end of Tx PB after 2 cycles and during FU
66
Giltritinib in RR AML
Admiral trial Phase III Compared to salvage Better CR and OS Most pts were not exposed to midostaurin
67
Giltritinib + Venetoclax in RR AML
Daver Phase I/II High CRi 75% OS 10 mon
68
GO Tx of favorable risk AML
For CBF and NPM1 Evidence is not clear in CEBPA Doesn't improve CR But it improves OS One study showed a loss of OS benefit in 5 years, but a matanalyiss confirmed the benefit.
69
Quazratinib in 1st line AML
QUANTUM-FIRST 3+7 backbonone Compared to placebo 18-75 OS advantage Limitation of not comparing to mido that was SOC
70
FLAG-IDA ven in AML
Approved slavage based on phase II (Di nardo) Good results from phase I/II studies in 1st line
71
AML subgrups in which ven not of benefit
p53 Monocytic
72
CEBPA diagnosis method
NGS Usually in time for tranplantation decision
73
APL transfusion thresholds
Fibrinogen 150 PLT 50K PT and aPTT close to normal values
74
Hydroxyurea in APL
To control WBC during ATRA Tx
75
ATRA dose in APL
45 mg/m2
76
Management of cytarabinae cerebellar toxicity
Hold Don't attempt high dose cytosar Tx
77
Suuportive care in pts Tx with high dose cytosar
Steroid eye drops Daily cerebellar exam
78
New low intensity induction for AML
LDAC+Cladribine + Venetoclax Alternating with VV Followed by VV Phase II High response rates. except in p53
79
All oral Tx for RR AML with NPM1/MLL
Revuminib+decatibine+venetoclax Phase I/II High response rates
80
Side effects of quizratinib
Hypokalemia Neutropenia PNA
81
VIALE-A pts
> 75 years or comorbities

Erez's HEM TEST notes 2024 (35 decks)

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