Acute myeloid leukemia, pediatric

Section editor transclusions This page contains studies that were specific to pediatric populations. For the more general AML page, follow this link.

14 regimens on this page 15 variants on this page

AAML1031 ARM A Low Risk

Induction I

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 1 - 30 minutes every 12 hours on days 1 through 10 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 1 - 30 minutes every 12 hours on days 1 through 10
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 1 - 15 minutes once per day on days 1, 3, 5 OR
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.7 mg/kg/dose IV over 1 - 15 minutes once per day
• Etoposide (Vepesid) 100 mg/m² IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

10-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Induction II

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 1 - 30 minutes every 12 hours on days 1 through 8 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 1 - 30 minutes every 12 hours on days 1 through 8
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 1 - 15 minutes once per day on days 1, 3, 5 OR
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.7 mg/kg/dose IV over 1 - 15 minutes once per day
• Etoposide (Vepesid) 100 mg/m² IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with bone marrow evaluation at the end of Induction I.
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

8-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Intensification I

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 - 3 hours every 12 hours on days 1 through 5 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 - 3 hours every 12 hours on days 1 through 5
• Etoposide (Vepesid) 150 mg/m²/dose IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 5 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with the bone marrow evaluation at the end of Induction II.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

5-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Intensification II

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 - 3 hours every 12 hours on days 1 through 4 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 - 3 hours every 12 hours on days 1 through 4
• Mitoxantrone (Novantrone) 12 mg/m² IV over 15 - 30 minutes once per day on days 3 through 6 OR
  • IF BSA < 0.6 m², Mitoxantrone (Novantrone) 0.4 mg/kg/dose once per day on days 3 through 6.
  • On days where both are given, give Mitoxantrone (Novantrone) 8 hours AFTER the END of the high dose Cytarabine (Ara-C) infusions.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with the bone marrow evaluation at the end of Intensification I.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

6-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

AAML1031 Arm A High Risk

Induction I

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 1 - 30 minutes every 12 hours on days 1 through 10 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 1 - 30 minutes every 12 hours on days 1 through 10
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 1 - 15 minutes once per day on days 1, 3, 5 OR
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.7 mg/kg/dose IV over 1 - 15 minutes once per day
• Etoposide (Vepesid) 100 mg/m² IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

10-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Induction II

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 - 3 hours every 12 hours on days 1 through 4 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 - 3 hours every 12 hours on days 1 through 4
• Mitoxantrone (Novantrone) 12 mg/m² IV over 15 - 30 minutes once per day on days 3 through 6 OR
  • IF BSA < 0.6 m², Mitoxantrone (Novantrone) 0.4 mg/kg/dose once per day on days 3 through 6.
  • On days where both are given, give Mitoxantrone (Novantrone) 8 hours AFTER the END of the high dose Cytarabine (Ara-C) infusions.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with the bone marrow evaluation at the end of Induction I.
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

6-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Intensification I

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 - 3 hours every 12 hours on days 1 through 5 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 - 3 hours every 12 hours on days 1 through 5
• Etoposide (Vepesid) 150 mg/m²/dose IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 5 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with the bone marrow evaluation at the end of Induction II.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

5-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Intensification II

Chemotherapy

• High Dose Cytarabine (Ara-C) 3000 mg/m²/dose IV over 3 hours every 12 hours on days 1, 2, 8, and 9.
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 100 mg/kg/dose IV over 3 hours every 12 hours on days 1, 2, 8, and 9
• E.Coli L-Asparaginase (LASP) 6000 international units/m²/dose IM on Day 2 (at hour 42) and Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8).
  • IF BSA < 0.6 m², E.Coli L-Asparaginase (LASP) 200 international units/kg/dose IM on Day 2 (at hour 42) and Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8).

may substitute with another asparaginase formulation

• Asparaginase Erwinia chrysanthemi (Erwinaze)

28-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

AAML1031 Arm C (FLT3/ITD+)

Induction I

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 1 - 30 minutes every 12 hours on days 1 through 10 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 1 - 30 minutes every 12 hours on days 1 through 10
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 1 - 15 minutes once per day on days 1, 3, 5 OR
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.7 mg/kg/dose IV over 1 - 15 minutes once per day
• Etoposide (Vepesid) 100 mg/m² IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5
• Sorafenib (Nexavar) 200 mg/m² PO once per day, rounded to accommodate tablet size on days 11 through 28
  • Max dose of 400 mg/dose, see Sorafenib Dosing Nomogram for more details.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

28-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Induction II

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 1 - 30 minutes every 12 hours on days 1 through 8 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 1 - 30 minutes every 12 hours on days 1 through 8
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 1 - 15 minutes once per day on days 1, 3, 5 OR
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.7 mg/kg/dose IV over 1 - 15 minutes once per day
• Etoposide (Vepesid) 100 mg/m² IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5
• Sorafenib (Nexavar) 200 mg/m² PO once per day, rounded to accommodate tablet size on days 9 through 36
  • Max dose of 400 mg/dose, see Sorafenib Dosing Nomogram for more details.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with bone marrow evaluation at the end of Induction I.
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

36-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Intensification I

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 - 3 hours every 12 hours on days 1 through 5 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 - 3 hours every 12 hours on days 1 through 5
• Etoposide (Vepesid) 150 mg/m²/dose IV over 60 - 120 minutes once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 5 mg/kg/dose IV over 60 - 120 minutes once per day on days 1 through 5
• Sorafenib (Nexavar) 200 mg/m² PO once per day, rounded to accommodate tablet size on days 6 through 33
  • Max dose of 400 mg/dose, see Sorafenib Dosing Nomogram for more details.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with the bone marrow evaluation at the end of Induction II.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

33-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

Intensification II

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 - 3 hours every 12 hours on days 1 through 4 OR
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 - 3 hours every 12 hours on days 1 through 4
• Mitoxantrone (Novantrone) 12 mg/m² IV over 15 - 30 minutes once per day on days 3 through 6 OR
  • IF BSA < 0.6 m², Mitoxantrone (Novantrone) 0.4 mg/kg/dose once per day on days 3 through 6.
  • On days where both are given, give Mitoxantrone (Novantrone) 8 hours AFTER the END of the high dose Cytarabine (Ara-C) infusions.
• Sorafenib (Nexavar) 200 mg/m² PO once per day, rounded to accommodate tablet size on days 7 through 34
  • Max dose of 400 mg/dose, see Sorafenib Dosing Nomogram for more details.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with the bone marrow evaluation at the end of Intensification I.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

6-day course

References

1. COG AAML1031: Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7). link to original article contains verified protocol NCT01371981

AAMLL0531 ARM B (Gemtuzumab)

Induction I

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 15 minutes every 12 hours on days 1 through 10
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 15 minutes every 12 hours on days 1 through 10
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 6 hours once per day on days 1, 3, and 5
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.67 mg/kg/dose IV over 6 hours once per day on days 1, 3, and 5
• Etoposide (Vepesid) 100 mg/m² IV over 4 hours once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 4 hours once per day on days 1 through 5
• Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV over 2 hours once on day 6
  • IF BSA < 0.6 m², Gemtuzumab ozogamicin (Mylotarg) 0.1 mg/kg/dose once on day 6.

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1
  • For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

10-day course

References

1. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

Induction II

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/dose IV over 15 minutes every 12 hours on days 1 through 8
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 3.3 mg/kg/dose IV over 15 minutes every 12 hours on days 1 through 8
• Daunorubicin (Cerubidine) 50 mg/m²/dose IV over 6 hours once per day on days 1, 3, and 5
  • IF BSA < 0.6 m², Daunorubicin (Cerubidine) 1.67 mg/kg/dose IV over 6 hours once per day on days 1, 3, and 5
• Etoposide (Vepesid) 100 mg/m² IV over 4 hours once per day on days 1 through 5 OR
  • IF BSA < 0.6 m², Etoposide (Vepesid) 3.3 mg/kg/dose IV over 4 hours once per day on days 1 through 5

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with bone marrow evaluation at the end of Induction I.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

28-day course

References

1. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

Intensification I

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 hour every 12 hours on days 1 through 5
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 hour every 12 hours on days 1 through 5
• Etoposide (Vepesid) 150 mg/m² IV over 1 hour once per day on days 1 through 5
  • IF BSA < 0.6 m², Etoposide (Vepesid) 5 mg/kg/dose IV over 4 hours once per day on days 1 through 5
  • Each dose of Etoposide (Vepesid) should immediately follow the AM dose of Cytarabine (Ara-C)

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with bone marrow evaluation at the end of Induction II.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

5-day course

References

1. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

Intensification II

Chemotherapy

• High Dose Cytarabine (Ara-C) 1000 mg/m²/dose IV over 1 hour every 12 hours on days 1 through 4
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 hour every 12 hours on days 1 through 4
• Mitoxantrone (Novantrone) 12 mg/m² IV over 1 hour once per day on days 3 through 6 OR
  • IF BSA < 0.6 m², Mitoxantrone (Novantrone) 0.4 mg/kg/dose once per day on days 3 through 6.
  • On days where both are given, give Mitoxantrone (Novantrone) 8 hours AFTER the END of the high dose Cytarabine (Ara-C) infusions.
• Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV over 2 hours once on day 7
  • IF BSA < 0.6 m², Gemtuzumab ozogamicin (Mylotarg) 0.1 mg/kg/dose once on day 7

CNS Prophylaxis

• Cytarabine (Ara-C) IT on day 1 or with bone marrow evaluation at the end of Intensification I.

Age	Dose
0 - 0.99	20
1 - 1.99	30
2 - 2.99	50
≥ 3	70

7-day course

References

1. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

Intensification III

Chemotherapy

• High Dose Cytarabine (Ara-C) 3000 mg/m²/dose IV over 3 hours every 12 hours on days 1, 2, 8, and 9.
  • IF BSA < 0.6 m², Cytarabine (Ara-C) 33 mg/kg/dose IV over 1 hour every 12 hours on days 1, 2, 8, and 9
• E.Coli L-Asparaginase (LASP) 6000 international units/m²/dose IM on Day 2 (at hour 42) and Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8).
  • IF BSA < 0.6 m², E.Coli L-Asparaginase (LASP) 200 international units/kg/dose IM on Day 2 (at hour 42) and Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8).

may substitute with another asparaginase formulation

28-day course

References

1. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

Upfront induction therapy

ADE (standard-dose Ara-C)

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ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
7-3-7: 7 days of Cytarabine, 3 days of Daunorubicin, 7 days of Etoposide
8-3-5: 8 days of Cytarabine, 3 days of Daunorubicin, 5 days of Etoposide
10-3-5: 10 days of Cytarabine, 3 days of Daunorubicin, 5 days of Etoposide

Regimen variant #1, 8-3-5, 1600/150/500, intermittent Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hann et al. 1997 (UK MRC AML10)	1988-1995	Phase III (E-switch-ic)	DAT 3+8	Did not meet efficacy endpoints
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase III (C)	See link	See link
Gamis et al. 2014 (COG AAML0531)	2006-2010	Non-randomized portion of RCT

Note: these trials have complicated treatment schemas; see papers for details. This is IND2 for COG AAML0531.

Preceding treatment

• UK MRC AML10: ADE 10-3-5 induction
• COG AAML0531: ADE 10-3-5 induction versus ADE & GO

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/day IV every 12 hours on days 1 to 8
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5
• Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5

8-day course

Subsequent treatment

• UK MRC AML10: MACE consolidation
• COG AAML0531: CYVE interim maintenance
• Other trials: Consolidation (see paper for details)

Regimen variant #2, 10-3-5, 2000/150/500, intermittent Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hann et al. 1997 (UK MRC AML10)	1988-1995	Phase III (E-switch-ic)	DAT 3+10	Did not meet efficacy endpoints
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase III (C)	See link	See link
Gamis et al. 2014 (COG AAML0531)	2006-2010	Phase III (C)	ADE & GO	Seems to have inferior EFS

Note: these trials have complicated treatment schemas; see papers for details.

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/day IV every 12 hours on days 1 to 10
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5
• Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

10-day course

Subsequent treatment

• ADE 8-3-5 re-induction

References

1. UK MRC AML10: Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. link to original article contains verified protocol PubMed
   1. Update: Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, Wheatley K; UK Medical Research Council Adult and Children's Leukaemia Working Parties. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet. 1998 Mar 7;351(9104):700-8. link to original article PubMed
2. UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
   1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
   2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
3. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

ADE (high-dose Ara-C)

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ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
HIDAC-3-5: HIgh-Dose Ara-C (Cytarabine), 3 days of Daunorubicin, 5 days of Etoposide
HIDAC-3-7: HIgh-Dose Ara-C (Cytarabine), 3 days of Daunorubicin, 7 days of Etoposide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Rubnitz et al. 2019 (AML08)	2008-2017	Phase III (C)	Clofarabine & Cytarabine	Seems to have superior MRD at day 22

Note: this regimen was intended for patients younger than 22 years.

Chemotherapy

• Cytarabine (Ara-C) 3000 mg/m² IV every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m²)
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 2, 4, 6
• Etoposide (Vepesid) 100 mg/m² IV once per day on days 2 to 6

6-day course

Subsequent treatment

• Response- and risk-adapted therapy; see paper for details

References

1. AML08: Rubnitz JE, Lacayo NJ, Inaba H, Heym K, Ribeiro RC, Taub J, McNeer J, Degar B, Schiff D, Yeoh AE, Coustan-Smith E, Wang L, Triplett B, Raimondi SC, Klco J, Choi J, Pounds S, Pui CH. Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial. J Clin Oncol. 2019 Aug 10;37(23):2072-2081. Epub 2019 Jun 27. link to original article link to PMC article contains verified protocol PubMed NCT00703820

ADE & GO

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ADE & GO: Ara-C (Cytarabine), Daunorubicin, Etoposidem, Gemtuzumab Ozogamicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Gamis et al. 2014 (COG AAML0531)	2006-2010	Phase III (E-RT-esc)	ADE 10-3-5	Seems to have superior EFS

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m²/day IV every 12 hours on days 1 to 10
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5
• Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

Antibody-drug conjugate therapy

• Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV over 2 hours once on day 6

10-day course

Subsequent treatment

• ADE 8-3-5 re-induction

References

1. COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed NCT00372593

AIE

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AIE: Ara-C (Cytarabine), Idarubicin, Etoposide
ICE: Idarubicin, Cytarabine, Etoposide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Entz-Werle et al. 2005 (EORTC 58921)	1992-2002	Phase III (C)	MEC	Did not meet efficacy endpoints

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m² IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m²)
• Idarubicin (Idamycin) 12 mg/m² IV over 30 minutes once per day on days 1 to 3
• Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

7-day course

References

1. EORTC 58921: Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y, Margueritte G, Plouvier E, Boutard P, Vandecruys E, Ferster A, Lutz P, Uyttebroeck A, Hoyoux C, Thyss A, Rialland X, Norton L, Pages MP, Philippe N, Otten J, Behar C; EORTC Children Leukemia Group. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia. 2005 Dec;19(12):2072-81. link to original article PubMed NCT00002517

DA 3 + 10

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DA 3 + 10: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine

Regimen variant #1, 50 mg/m² dauno

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase III (C)	See link	See link

Note: this regimen is very similar to 7+3d (standard-dose); however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 10
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5

10-day course

Subsequent treatment

• See papers for details (to be completed).

References

1. UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
   1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
   2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed

DA 3 + 10, GO

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DA 3 + 10, GO: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine, Gemtuzumab Ozogamicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase III (E-esc)	See link	See link

This trial has complicated treatment schemas; see papers for details.

Chemotherapy

• Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 10
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5

Antibody-drug conjugate therapy

• Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV once on day 1

10-day course

Subsequent treatment

• See paper for details (to be completed).

References

1. UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
   1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
   2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed

FLAG-Ida

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FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Lenograstim), Idarubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase III (C)	1. ADE 10+3+5 2. DA 3+10 3. DA 3+10 & GO 4. FLAG-Ida & GO	Did not meet primary endpoint of OS1

¹While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.

Chemotherapy

• Fludarabine (Fludara) 30 mg/m² IV once per day on days 2 to 6
• Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 2 to 6, given 4 hours after fludarabine
• Idarubicin (Idamycin) 8 mg/m² IV once per day on days 4 to 6

Growth factor therapy

• Lenograstim (Granocyte) 263 mcg SC once per day on days 1 to 7

7-day course

Subsequent treatment

• See paper for details

References

1. UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
   1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
   2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed

Consolidation after upfront therapy

BuCy, then auto HSCT

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BuCy: Busulfan & Cyclophosphamide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ravindranath et al. 1996	1988-1993	Phase III (E-esc)	Intensive chemotherapy	Did not meet primary endpoint of EFS24

Preceding treatment

• 7+3d, then HiDAC

Chemotherapy

• Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -9 to -6
• Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days -5 to -2

Supportive therapy

• Autologous stem cells re-infused on day 0

One course

References

1. Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. link to original article contains verified protocol PubMed

Cyclophosphamide & TBI, then allo HSCT

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Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study	Evidence
Brochstein et al. 1987	Non-randomized

Details in most of the manuscripts are limited.

Chemotherapy

• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Radiotherapy

• Total body irradiation by the following study-specific criteria:
  • Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
  • Other studies: 10 to 1200 cGy total

Immunotherapy

• Allogeneic stem cells transfused on day 0

One course

Immunotherapy

• Allogeneic stem cells

Stem cells transfused on day 0

References

1. Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. link to original article PubMed

Relapsed or refractory, salvage therapy

Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.

FLAG

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FLAG: FLudarabine, Ara-C (Cytarabine), G-CSF

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kaspers et al. 2013 (I-BFM-SG 2001/01)	2001-2009	Phase III (C)	FLAG-DNX	Seems to have inferior CR rate

Note: this regimen was studied in patients up to 21 years of age.

Chemotherapy

• Fludarabine (Fludara) 30 mg/m² IV once per day on days 1 to 5, given second
• Cytarabine (Ara-C) 2000 mg/m² IV once per day on days 1 to 5, given third, 4 hours after the start of fludarabine

Growth factor therapy

• Filgrastim (Neupogen) 200 mcg/m² (route not specified) once per day on days 0 to 5, given first

2 cycles (length not specified)

Subsequent treatment

• CYVE or Cytarabine & Thioguanine consolidation, as a bridge to allogeneic HSCT

References

1. I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains verified protocol PubMed NCT00186966

Consolidation after salvage therapy

Cytarabine & Thioguanine

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Regimen

Study	Evidence
Kaspers et al. 2013 (I-BFM-SG 2001/01)	Non-randomized portion of RCT

Note: this regimen was studied in patients up to 21 years of age, and was intended for use when the time to transplant would be relatively short or for patients in "poor condition".

Preceding treatment

• FLAG versus FLAG-DNX

Chemotherapy

• Cytarabine (Ara-C) 75 mg/m² SC once per day on days 1 to 4
• Thioguanine (Tabloid) as follows:
  • Cycles 1 & 2: 100 mg/m² PO once per day

14-day cycles

Subsequent treatment

• Allogeneic HSCT

References

1. I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains verified protocol PubMed NCT00186966

CYVE

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CYVE: CYtarabine & VEpesid (Etoposide)

Regimen

Study	Evidence
Kaspers et al. 2013 (I-BFM-SG 2001/01)	Non-randomized portion of RCT

Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.

Preceding treatment

• FLAG versus FLAG-DNX

Chemotherapy

• Cytarabine (Ara-C) 500 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m²)
• Etoposide (Vepesid) 100 mg/m² IV twice per day on days 1 to 4

Subsequent treatment

• allogeneic HSCT

References

1. I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains verified protocol PubMed NCT00186966