AML Flashcards
What cytogenetic abnormalities qualify as AML regardless of the blast count?
t(8;21), inv (16), t(16;16), and t(15;17)
What are some favorable risk cytogenetics for AML?
Biallelic mutated CEBPA, mutated NPM1 w/o FLT3 ITD or with FLT3 ITD low, inv 16, t(16;16), t (8;21) RUNX1/RUNX1T1
Wild type NPM1 and FLT-3 ITD high confer what kind of risk in AML?
High risk disease!
Mutated RUNX1, ASXL1, and TP53 mutation carry what kind of risk in AML?
High risk disease
In regards to NPM1 mutations what are the combinations that give you intermediate risk disease?
Mutated NPM1 and FLT3 ITD high, wild type NPM w/o FLT-3 ITD or with FLT3-ITD low
What is the typical translocation found in APL?
t(15;17) PML;RARA
What is a atypical chromosome translocation that can be seen in APL? What is the clinical significance?
t(11;17) This translocation is not responsive to ATRA, you will need to use AML directed chemo
What is defined as high risk APL and what is the tx?
Greater than 10 K WBC, you start dexamethasone.
What are the flow results for APL?
HLA-DR-, CD33, CD13+, CD34-
What are the tx options for high risk APL?
ATRA/ATO plus Gemtuzumab Ozogamicin
ATRA/ATO plus Idarubicin or Daunarubicin
What is the induction regimen used for FLT3 ITD or TKD?
- 7+3 (dauno or Ida) w/midostaurin (ITD or TKD)
- 7+3 (dauno or Ida) w quizartinib (ITD only)
What induction regimens do you use for low risk AML?
- 7+3 (daunorubicin)+Gemtuzumab (preferred regimen).
- 7+3 (w/daunorubicin or Ida)
- 7+3 (mitoxantrone)
What is tx for intermediate risk AML?
7+3 (dauno or Ida)
7+3 (mitoxantrone) for 60 and older
What is the induction regimen preferred for TP53 and/or del17p?
- 7+3 (cat 1 rec)
- 7+3 (mitoxantrone) for 60 and older
- HiDAC+ dauno or Ida+ Etoposide (cat 1 rec)
What is the tx for therapy induced AML or antecedent MDS/CMML or MDS related cytogenetic changes (that define AML)?
- 7+3
- Vyxeos (liposomal daunorubicin and cytarabine) (only for age 60 or older)
- Azacitidine or Decitabine w/Venetoclax
What is the mechanism of action of Gemtuzumab?
It is a antibody drug conjugate against CD33, callcheamicin is released causing double stranded DNA breakage
When using Gemtuzumab the benefit was only shown in what group of AML patients?
There is only a OS benefit with good risk disease.
What is the induction regimen of choice in elderly patients or those less fit with multiple comorbidities?
Ven with Aza or Decitabine or low dose Cytarabine. ASH also mentions Glasdegib plus low dose cytarabine-assoc with OS benefit.
Gilteritinib is approved for what?
Adults with relapsed/refractory FLT3 mutated AML.
For those with IDH1 mutation what treatment should these patients receive? What is the specific indication?
Ivosidenib w/Azacitidine, associated with OS benefit. When giving with Azacitidine you give it to patients with newly diagnosed AML who are 75 years or older or unfit for intensive chemo. NCCN also mentions severe cardiac/pulmonary dx, CrCl less than 45, T bili of 1.5 or higher. Can also give it alone for upfront tx (those that aren’t eligible for intense upfront tx). You also give it to patients with relapsed disease.
What treatment do you give for IDH2 mutation and what is the indication?
You give Enasidenib to those for induction therapy (those that aren’t eligible for strong induction regimen) or for relapsed/refractory disease with a IDH2 mutation. Enasidenib w/Aza is Cat 2 Rec.
What are the side effects seen with Ivosidenib and Enasidenib?
Ivosidenib-diarrhea, pyrexia, fatigue
Enasidenib-nausea, fatigue, increased bilirbuin, diarrhea.
Differentiation syndrome for both!
What are the tx options for relapsed disease if you have a FLT3 ITD mutation?
Gilternitib or Azacitidine/Decitabine plus Sorafenib
What are the tx options for relapsed disease with FLT3-TKD? IDH 1 and 2?
Gilternitib alone-TKD
IDH1-Ivosidenib and Olutasenidib
IDH2-Enasidenib
What is the treatment for relapsed CD33 AML?
Gemtuzumab
What are intensive regimens that you can use in relapsed/refractory disease? May not have to remember this, but just be familiar
Cladribine + cytarabine + G-CSF ± mitoxantrone or idarubicin
HiDAC (if not received previously in treatment) ± (idarubicin or
daunorubicin or mitoxantrone)
For less fit patients with relapsed disease what do you do?
HMA plus Venetoclax
Venetoclax plus low dose Cytarabine. HMA alone or low dose ARA-C alone. Low dose ARA-C is cat 2 rec.
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?
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.
What patients should receive maintenance therapy?
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).
After a patient completes induction therapy when do you perform a repeat BM biopsy?
After standard dose cytarabine: 14-21 days
After high dose Cytarabine for poor risk disease: 21-28 days
When using FLT3 inhibitors in the maintenance setting who does this apply to?
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.
