AML

Question 1

What cytogenetic abnormalities qualify as AML regardless of the blast count?

Answer 1

t(8;21), inv (16), t(9;11), t(6;9), inv3, mutated NPM1, in frame bZIP mutated CEBPA, t(9;22), and t(15;17)

Question 2

What are some favorable risk cytogenetics for AML?

Answer 2

Biallelic mutated CEBPA (bZIP in frame mutated CEBPA), mutated NPM1 w/o FLT3 ITD or with FLT3 ITD low, inv 16, t(16;16), t (8;21)-RUNX1/RUNX1T1

Question 3

Wild type NPM1 and FLT-3 ITD high confer what kind of risk in AML?

Answer 3

Intermediate risk disease. (take note the previous answer I had here was high risk, but looking at resources it is intermediate risk)

Question 4

Mutated RUNX1, ASXL1, and TP53 mutation carry what kind of risk in AML?

Answer 4

High risk disease

Question 5

In regards to NPM1 mutations what are the combinations that give you intermediate risk disease? What other cytogenetic translocation qualifies as intermediate risk disease?

Answer 5

Mutated NPM1 and FLT3 ITD high, wild type NPM w/ FLT-3 ITD or without FLT-3 ITD or FLT3 ITD low
t(9;11)

Question 6

What is the typical translocation found in APL?

Answer 6

t(15;17) PML;RARA

Question 7

What is a atypical chromosome translocation that can be seen in APL? What is the clinical significance?

Answer 7

t(11;17) This translocation is not responsive to ATRA, you will need to use AML directed chemo

Question 8

What is defined as high risk APL and what is the tx?

Answer 8

Greater than 10 K WBC, you start dexamethasone.

Question 9

What are the flow results for APL?

Answer 9

HLA-DR-, CD33, CD13+, CD34-

Question 10

What are the tx options for high risk APL?

Answer 10

ATRA/ATO plus Gemtuzumab Ozogamicin (preferred)
ATRA/ATO plus Idarubicin (preferred)
You can use ATRA with Daunorubicin and Cytarabine if ATO for some reason is contraindicated or ATRA with Idarubicin as well

Question 11

What is the induction regimen used for FLT3 ITD or TKD?

Answer 11

1. 7+3 (dauno or Ida) w/midostaurin (ITD or TKD)
2. 7+3 (dauno or Ida) w quizartinib (ITD only)

Question 11

What induction regimens do you use for low risk core binding AML? t(8;21), inv 16, t(16;16)

Answer 11

1. 7+3 (daunorubicin)+Gemtuzumab (CD33+) (preferred regimen).
2. 7+3 (w/daunorubicin or Ida)
3. 7+3 (mitoxantrone) age>60

Question 12

What is tx for favorable risk by molecular mutation (mutated NPM1 w/o FLT3 mutation, bZIP in frame mutation of CEBPA) and intermediate risk AML?

Answer 12

7+3 (dauno or Ida) (Cat 1)
7+3 (mitoxantrone) for 60 and older

Question 13

What is the induction regimen preferred for TP53 and/or del17p?

Answer 13

New updated recommendation per NCCN: Clinical Trial. Below are the older recommendations:
1. 7+3 (cat 1 rec)
2. 7+3 (mitoxantrone) for 60 and older
3. HiDAC+ dauno or Ida+ Etoposide (cat 1 rec)

Question 14

What is the induction therapy for therapy induced AML or antecedent MDS/CMML/ MDS related cytogenetic changes (meaning they had MDS transform to AML)?

Answer 14

1. 7+3 (for less than age 60) (preferred)
2. CPX-351 Vyxeos (liposomal daunorubicin and cytarabine) (only for age 60 or older) (preferred)
3. Azacitidine or Decitabine w/Venetoclax

Question 15

What is the mechanism of action of Gemtuzumab?

Answer 15

It is a antibody drug conjugate against CD33, callcheamicin is released causing double stranded DNA breakage

Question 16

When using Gemtuzumab the benefit was only shown in what group of AML patients?

Answer 16

There is only a OS benefit with good risk disease.

Question 17

What is the induction regimen of choice in elderly patients or those less fit with multiple comorbidities w/a IDH1? What if they don’t have a IDH1 mutation?

Answer 17

IDH1: Ven with Aza (Cat 1) or Decitabine. Azacitidine with Ivosedenib (Cat 1). Ivosedenib alone is an option, just not preferred.
No IDH1: Azacitidine w/Venetoclax (Cat 1) or Decitabine w/Venetoclax

Question 18

Gilteritinib is approved for what?

Answer 18

Adults with relapsed/refractory FLT3 mutated AML, both ITD and TKD.

Question 19

What treatment do you give for IDH2 mutation and what is the indication?

Answer 19

Updated guidelines: Enasidenib for relapsed/refractory disease with a IDH2 mutation.

Question 20

What are the side effects seen with Ivosidenib and Enasidenib?

Answer 20

Ivosidenib-diarrhea, pyrexia, fatigue
Enasidenib-nausea, fatigue, increased bilirbuin, diarrhea.
Differentiation syndrome for both!

Question 21

What are the tx options for relapsed disease if you have a FLT3 ITD mutation?

Answer 21

Gilternitib or Azacitidine/Decitabine plus Sorafenib
Quizartinib-Cat 2B

Question 22

What are the tx options for relapsed disease with FLT3-TKD? IDH 1 and 2?

Answer 22

Gilternitib alone-TKD
IDH1-Ivosidenib and Olutasenidib
IDH2-Enasidenib

Question 23

What is the treatment for relapsed CD33 AML?

Answer 23

Gemtuzumab

Question 24

What are intensive regimens that you can use in relapsed/refractory disease? May not have to remember this, but just be familiar

Answer 24

Cladribine + cytarabine + G-CSF ± mitoxantrone or idarubicin Cytarabine +/- Daunorubicin or Idarubicin or Mitoxantrone Fludarabine + Cytarabine + GCSF +/- Idarubicin +/- Venetoclax (FLAG) Etoposide+Cyatarbine +/- Mitoxantrone

Question 25

For less fit patients with relapsed disease what do you do?

Answer 25

HMA plus Venetoclax Venetoclax plus low dose Cytarabine. HMA alone or low dose ARA-C alone. Low dose ARA-C is cat 2 rec.

Question 26

What do you do for patients after induction therapy if they have hypoplastic disease with blasts less than 5%? When should the marrow be performed?

Answer 26

You should repeat marrow once plt>100 and ANC>1000. If not by day 35 this is achieved you do another marrow. If still no count recovery, you repeat marrow in 1 week. Marrow should be performed 3-4 weeks after induction treatment. If they say the marrow was done early then you wait.

Question 27

What patients should receive maintenance therapy?

Answer 27

For those who don't undergo alloSCT, completed some or no consolidation or all of it. Options: Oral Aza or IV Aza or Decitabine (these options you only give for intermediate or poor risk disease). Decitabine is a category 2 Rec. If you have a FLT3 mutation you can use the appropriate options (for those that received a SCT). ASCO says to use oral Azacitidne.

Question 28

After a patient completes induction therapy when do you perform a repeat BM biopsy?

Answer 28

After standard dose cytarabine: 14-21 days After high dose Cytarabine for poor risk disease: 21-28 days

Question 29

When using FLT3 inhibitors in the maintenance setting who does this apply to?

Answer 29

So for all the FLT3 inhibitors you give these to patients who have received a SCT. Quizartinib (ITD only) can be given to patients who did not receive a SCT and previously received Quizartinib.

Question 30

When a patient is getting treated with Cytarabine for consolidation therapy and develops neurotoxicity, what is the best next step?

Answer 30

Stop therapy right away and switch to a new therapy. If they are getting this as consolidation therapy, then you should switch to allogeneic transplant if they are a candidate.

Question 31

What induction regimens do you use for low risk APL?

Answer 31

ATRA plus daily ATO or intermittent ATO, both are Cat 1. If ATO is contraindicated you can use ATRA plus Idarubicin (Cat 1) or Gemtuzumab

Question 32

Remember what are the two morphological variants of APL and which one is the most common?

Answer 32

Hypergranular-80% Microgranular-20%

Question 33

What consolidation therapy do you offer a patient with good risk AML that responds to induction therapy?

Answer 33

Cytarabine +/- Gemtuzumab if given w/induction Cytarabine for 5-7 days +/- Daunorubicin/Idarubicin or Mitoxantrone (for 60 years or older) Cytarabine plus Idarubicin or Daunorubicin plus Gemtuzumab

Question 34

What do we offer for consolidation therapy for patients who have FLT3 ITD or TKD disease?

Answer 34

Allogeneic transplant is preferred for patients who have FLT3 ITD mutation. Can also use Cytarabine plus Midostaurin for ITD or TKD mutation Cytarabine plus Quizartinib (ITD mutation only)

Question 35

What is offered for consolidation therapy for those patients that have intermediate disease?

Answer 35

Ultimately these patients need a allogeneic SCT so they can go directly for this or undergo 1-2 cycles consolidation tx of (while doing donor search): Cytarabine alone Cytarabine plus Idarubicin or Daunorubicin plus Gemtuzumab

Question 36

What is the timeline that you use when determining if a patient can be retreated with Atra +/- ATO in relapsed APML?

Answer 36

If the relapse occurred 6 months or longer after the initial treatment then they can be retreated with Atra +/-ATO +/- Anthracycline or Gemtuzumab.

Question 37

In the second relapse for APML after they respond to reinduction what should the next best step be?

Answer 37

If they are candidate for transplant they should undergo a auto transplant if BM is negative for disease or allo SCT if the BM is positive for disease. If they aren't then you give ATO x6 cycles for consolidation therapy. You should also consider getting IT chemo for CNS prophylaxis w/MTX or Cytarabine.

Question 38

What is the best next step for a patient who has APML that has relapsed less than 6 months?

Answer 38

ATRA plus daunorubicin or Idarubicin. You can also consider using Gemtuzumab.

Question 39

What are the recommended induction options for poor risk AML with deletion 17p or Tp53? Wo Tp53?

Answer 39

Tp53: Clinical trial is the preferred answer. W/o Tp53: 7+3, CPX-351 (Lipo Dauno+Cytarabine) (Cat 2B), FLAG-IDA (Cat 2B), Decitabine/Azacitidine+Venetoclax

Question 40

When a patient fails induction therapy, what are the treatment options to consider? For FLT3 mutation?

Answer 40

Cytarabine, 7+3 (Daunorubicin or Idarubicin), 5+2 (mitoxantrone for age 60 or older) or can give with Daunorubicin or Idarubicin, 7+3 mitoxantrone for age 60 or older). FLT3: use 7+3 with Midostaurin (TKD and ITD) Other regimens you use for refractory disease

Question 41

What are the clinical features of SOS (formerly VOD), what is the treatment and what can you give for prophylaxis?

Answer 41

Increase in bili greater than 2, painful hepatomegaly or RUQ, weight gain (above 2% from baseline). Defibrotide can be given as treatment in addition to supportive care and given as prophylaxis.

Question 42

High dose Daunorubicin 90 mg/m2 benefits what prognostic groups of AML and what age?

Answer 42

Favorable and intermediate risk. Less than 65 years of age. DNMT3A is a intermediate risk factor.

Question 43

High dose Ara-C is contraindicated for which age group?

Answer 43

Patients aged 60 years or older per NCCN

Question 44

When can you give chemo to a pregnant patient and what agents can you use?

Answer 44

After the first trimester, so after 13 weeks. You can use 7+3 therapy, so yes it's okay to use an anthracycline. Yes there is still the risk of fetal death/other complications.

Question 45

What are cytogenetic features that classify someone as having high risk AML?

Answer 45

t(6;9), inv3, t(9;22), t(8;16), t(v;11q23.30)KMT2A rearranged, -5 or del 5q, del 7, del 17p, complex karyotype, Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2i t(3q26.2;v)/MECOM (EVI1)-rearranged

Question 46

CPX-351 Vyxeos is approved for what patients?

Answer 46

Patients aged 60-75 with AML transformed in the prior presence of MDS, treatment related MDS, or CMML