1. AML2012 Overview MEC R1 BM d22* R AD(x)E FLAD(x) HAM HA3E FLA BM**
SCT for HR CR
No CR
Salvage therapy
Inv(16)
and SR

2. MEC MEC Cytarabine 200 mg/m2 12h ci iv Mitoxantrone 5 mg/m2 iv
Mtx it*
Cytarabine 200 mg/m2 12h ci iv
Etoposide 150 mg/m2 iv
Mitoxantrone 5 mg/m2 iv
Day 6-12
Day 6-10 Inf 1 hour
Day 1-5 Inf 2 hours
Day 1 2 3 4 5 6 7 8 9 10 11 12
MEC
Mtx it age-adjusted
<1y 6 mg
1-<2y 8 mg
2-<3y 10 mg
≥ 3y 12 mg
Children < 1y or < 10kg
Cytarabine 6.7 mg/kg
Etoposide 5 mg/kg
Mitoxantrone 0.17 mg/kg

3. AD(x)E Cytarabine 100 mg/m2 ci Cytarabine 100 mg/m2 iv
Mtx it
Cytarabine 100 mg/m2 iv
Etoposide 150 mg/m2 iv
(liposomaal) Daunorubicine
60 mg/m2 iv
Day 3-8, 30 min inf, every 12h
Day 2,4,6 1 hour inf
Day 6,7,8 2 hour
Day 1 2 3 4 5 6 7 8
Cytarabine 100 mg/m2 ci
Day 1,2
Mtx it age-adjusted
<1y 6 mg
1-<2y 8 mg
2-<3y 10 mg
≥ 3y 12 mg
Children < 1y or < 10kg
Cytarabine 3.3 mg/kg
Etoposide 5 mg/kg
Daunoxome 2 mg/kg

4. FLAD(x) Fludarabine 30 mg/m2 iv (30min) Cytarabine 2000 mg/m2 inf (3h)
(liposomaal)Daunorubicine
60 mg/m2 iv inf (1h)
Day
Day 1-5
Day 1-5 4h after fludarabine
Day 2,4,6 immediately after fludarabine
Mtx it 1 5 6 4 3 2
Mtx it age-adjusted
<1y 6 mg
1-<2y 8 mg
2-<3y 10 mg
≥ 3y 12 mg
Children < 1y or < 10kg
Cytarabine 67 mg/kg
Fludarabine 1 mg/kg
Daunoxome 2 mg/kg

5. Overview of consolidation
Inv(16)
HA3E
FLA
Standard risk
HAM
HA3E
FLA
No donor
High risk
HAM
SCT
Note that SR patients with Inv(16)
only receive two consolidation blocks

6. HAM Cytarabine 1000 mg/m2 inf (2h)
Mitoxantrone 10 mg/m2 iv inf (1 hour)
Day 1-3 every 12 hours
Day 3,4,5
Mtx it
Day 1 5 4 3 2
Mtx it age-adjusted
<1y 6 mg
1-<2y 8 mg
2-<3y 10 mg
≥ 3y 12 mg
Children < 1y or < 10 kg
Cytarabine 33 mg/kg
Mitoxantrone 0.33 mg/kg

7. HA3E Cytarabine 3000 mg/m2 inf (2h) Etoposide 100 mg/m2 inf (1h)
Day 1-3 every 12 hours
Day 1-5
MTX it
Day 1 5 4 3 2
Mtx it age-adjusted
<1y 6 mg
1-<2y 8 mg
2-<3y 10 mg
≥ 3y 12 mg
Children < 1y or < 10 kg
Cytarabine 67 mg/kg
Fludarabine 1 mg/kg
Daunoxome 2 mg/kg

8. FLA Fludarabine 30 mg/m2 iv (30min) Cytarabine 2000 mg/m2 inf (3h)
Day
Day 1-5
Day 1-5 4h after fludarabine
Mtx it 1 5 4 3 2
Mtx it age-adjusted
<1y 6 mg
1-<2y 8 mg
2-<3y 10 mg
≥ 3y 12 mg
Children < 1y or < 10kg
Cytarabine 67 mg/kg
Fludarabine 1 mg/kg
Daunoxome 2 mg/kg

9. Flowsheet induction BM + MRD Repeat BM + MRD weekly Start course 2
Day 22 after course 1
Repeat BM + MRD weekly
until recovery of ANC and platelets
Start course 2
immediately
day after course 2
Salvage therapy
If very aplastic BM consider
repeat BM – see protocol text
LC ≥ 5%
LC < 5%
on recovery after course 1
LC < 5% and recovery
start HAM
LC ≥ 0.1% assign HR
BM +MRD + HAM*
On recovery after course 2
LC before HAM ≥ 0.1%
assign HR
LC ≥ 15%
Assign HR
Assign RD

10. AML2012
Flow MRD sampling

11. Induction MRD Standard risk patients MRD before course 5*
Diagnosis – MRD target search
Day 22 – MRD all patients
Good Response < 5% LC
MRD repeated weekly
Start course one
Start course two
Poor Response ≥ 5% LC
Course 2 direct
after regeneration
MRD before consolidation
MRD D22
Poor Response
Off protocol
Good Response
Start consolidation
High risk patients
MRD before SCT

12. Consolidation MRD High risk patients MRD before SCT
Standard risk patients
MRD before course 5
The exact number of MRD samples
cannot be determined but it is
expected that 3-4 samples per
patient will be taken during induction