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AML Flashcards

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1
Q

Threshold concerning for leukostasis in AMl

A

50k

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2
Q

What is considered treatment related AML?

A

Exposure to prior chemo, radiation, or ***immunosuppressive drugs

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3
Q

Gene mutation associated with topoisomerase II inhibitors in AML

A

11q23 (II looks like an 11)

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4
Q

Timeframe for treatment related AmL from topoisomerase exposure

A

1-3 years post treatment
*No MDS phase

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5
Q

Drug classes associated with therapy related AML

A
  • anthracyclines (topoisomerase II)
  • alkylating agents (eg cytoxan)
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6
Q

Cytogenetic abnormalities associated with exposure to alkylating agents in AML

A

5 and 7 deletions (present 5 and 7 years after)

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7
Q

Timeframe for treatment related AML from alkylating agents

A

5-7 years
*preceeding MDS phase

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8
Q

Change in CEBPA classification for favorable risk category

A
  • not biallelic. It’s now any bzip in frame mutated CEBPA
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9
Q

Risk stratification of FLT3 in AML

A

All intermediate now regardless of NPM1 (improved outcomes from FLT3 targeted therapy)

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10
Q

Indications for LP for de novo AML

A

1) WBC>30K
2) monocytic or myelomonocytic
3) FLT3 mutant
AND symptomatic

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11
Q

Initial management of leukostasis

A
  • hydrea
  • Given myeloid lineage on flow, 1-2 g cytarabine (can also be used) vs. cytoxan
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12
Q

Allopurinol mechanism of action

A

inhibits xanthine oxidase

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13
Q

Rasburicase mechanism of action

A

catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite allantoin

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14
Q

What is core binding factor AML?

A

AML with inv(16) or t(8;21)

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15
Q

Standard of care for CBF AML

A

7+3 + gemtuzumab ozogamicin (dramatic improvement in outcomes)

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16
Q

1) gemtuzumab mechanism 2) SE’s to know with gemtuzumab

A
  • increased risk of VOD (sinusoidal obstruction syndrome)
  • myelosuppression
  • increased liver toxicity
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17
Q

generic name of vyxeos

A

liposomal-daunorubicin/cytarabine

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18
Q

Treatment options for frail patient that is IDH1 mutant

A

1) HMA + venetoclax
2) HMA + ivosidenib 500 mg daily for at least 2 years + HMA q28 days (Preferred -AGILE - OS 24 vs. 8 months)

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19
Q

High dose cytarabine (HiDAC) SE to know + management

A
  • cerebellar toxicity
  • permanent discontinuation
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20
Q

Prophylaxis required when giving HiDAC

A

Steroid eye drops

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21
Q

Blast cutoff for AML diagnosis

A

Greater than 20%

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22
Q

What is 7 + 3

A

7 days cytarabine
3 days anthracycline

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23
Q

IDH1 targeted drug

A

Ivosidenib

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24
Q

IDH2 targeted drug

A

Enasidenib

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25
AML immunophenotype
CD13+, CD33+, MPO+, CD34+
26
Morphologic CR in AML
<5% blasts
27
Consolidation for patient requiring 2 inductions in AML in CR2
Allo-HSCT
28
Options for relapsed/refractory AML - "remission reinduction"
1) salvage combination chemotherapy followed by allo-HSCT (Phase 2 -- impressive response rates but very toxic) 2) HMA + venetoclax if not received upfront, then allo-HSCT 3) Clinical trial followed by allo-HSCT 4) Add targeted therapy if available: Given IDH mutation, add IDH inhibitor to regimen, e.g. HMA/venetoclax Given FLT3 ITD or TKD mutant (prior FLT3 doesn’t exclude), gilteritinib followed by allo-HSCT (OS benefit) Given CD33 and not used previously, gemtuzumab followed by allo-HSCT
29
Most commonly used systemic therapy regimens for re-induction
(FLAG-IDA + venetoclax) MEC
30
What is FLAG-IDA?
Fludarabine, cytarabine, plus G-CSF , idarubicin
31
What is MEC?
M - mitoxantrone E - etoposide C - cytarabine
32
Favorable risk AML mutations
1) t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 2) inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11 3) Mutated NPM1 without FLT3-ITD 4) bZIP in-frame mutated CEBPA
33
Other AML RF's
Benzene
34
Germline mutations associated with increased risk of AML
CEBPA DDX41
35
AML defining genetic abnormalities
*NPM1 + RUNX1:RUNX1 + CBFB:MYH11 + DEK::NUP214 + RBM15::MRTFA fusion + KMT2A + MECOM + NUP98 + CEBPA
36
What is the answer in terms of genetic abnormality with question showing peripheral smear full of eosinophils?
AML with inversion 16
37
Management of AML with inversion 16
gemtuzumab
38
What is AML-MRC?
AML with myelodysplasia related changes?
39
Board answer to management of Down syndrome patient with MPN + mutation
- observation (erythromegakaryocytic MPN, it spontaneously resolves over the first few months of life) - GATA1
40
Genetic abnormality for patient presenting with basophilia
t(6;9)
41
Genetic abnormality associated with AML presenting with thrombocytosis
inv(3) or T(3;3)
42
What does quizartinib target
FLT3-ITD *not TKD
43
Giltertinib approval
Relapsed/refractory, not induction
44
Common mutation in therapy related AML
TP53 (30-40%)
45
Management of p53 mutant AML
clinical trial (we have no good standard therapies)
46
Standard for defining who is ineligible for induction chemotherapy in AML
- Age >75 - CHF requiring treatment or EF <50% - DLCO <65% or FEV1 <65% - ECOG 2-3, can be disease dependent
47
Board answer for elderly patient unfit for induction chemo
HMA + venetoclax
48
Venetoclax dosing w/ HMA + venetoclax
- continuous is board answer - small but compelling abstract for 14 days so a lot of centers are using 14 day dosing
49
New IDH inhibitor recently approved
olutasidenib (only approved in relapsed/refractory setting)
50
Preferred conditioning and clinical benefit for patients MRD+ prior to transplant
- myeloablative conditioning (OS benefit vs. RIC w/ genomic evidence of disease prior to transplant)
51
Age as a RF for AML
Age over 65 is an independent predictor of poor prognosis
52
Caveat to genetically defined AML
Has to be at least 10% blasts in marrow or blood
53
Indication for germline testing in AML
Age <40 years
54
Role for maintenance azacitidine
Approved for pts >55 in CR1 who aren't candidates for intensive consolidation therapy
55
t(6;9) risk stratification
adverse
56
Induction therapy for CBF AML patients with CHF
Fludarabine, cytarabine, GCSF, and gemtuzumab
57
What is the role of gemtuzumab in AML induction?
- approved in addition to 7+3 in adults with intermediate or favorable (NOT adverse) but truth is results have been mixed from trials
58
Basic physiology of NPM1 mutation
Abnormal nuclear export signal
59
Clinical significance of -7
high risk
60
Preferred conditioning regimens
IF significant comorbidities (DM1, cardiac), reduced intensity IF fit, myeloablative
61
Preferred reduced intensity conditioning regimen
Fludarabine, busulfan
62
What are the myeloablative conditioning regimens
- cyclophosphamide/busulfan - cyclophosphamide, TBI - Etoposide, TBI
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