Difference between revisions of "Acute myeloid leukemia, pediatric"

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{{TOC limit|limit=4}}
 
{{TOC limit|limit=4}}
 
 
=Guidelines=
 
=Guidelines=
 
=="How I Treat"==
 
=="How I Treat"==
 
*'''2021:''' Rubnitz & Kaspers [https://doi.org/10.1182/blood.2021011694 How I treat pediatric acute myeloid leukemia]
 
*'''2021:''' Rubnitz & Kaspers [https://doi.org/10.1182/blood.2021011694 How I treat pediatric acute myeloid leukemia]
 
 
=Upfront induction therapy=
 
=Upfront induction therapy=
 
==COG AAML1031 arm A (low-risk)==
 
==COG AAML1031 arm A (low-risk)==
===Protocol===
+
<div class="toccolours" style="background-color:#eeeeee">
====Chemotherapy, induction I====
+
===Induction, part I===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10  
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
Line 59: Line 59:
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1  
 
*[[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)
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
**
 
**
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 81: Line 79:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''10-day course, followed by:'''
 
'''10-day course, followed by:'''
 
+
</div></div><br>
====Chemotherapy, induction II====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Induction, part II===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*[[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
*[[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 8  
 
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 8  
Line 95: Line 94:
 
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
*[[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).  
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).  
 
**
 
**
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 117: Line 114:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''8-day course, followed by:'''
 
'''8-day course, followed by:'''
 
+
</div></div><br>
====Chemotherapy, Intensification I====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Intensification, part I===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
*High Dose [[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5  
 
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5  
Line 128: Line 126:
 
**BSA 0.6 m<sup>2</sup> or more: 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 through 5  
 
**BSA 0.6 m<sup>2</sup> or more: 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 through 5  
 
**BSA < 0.6 m<sup>2</sup>: 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**BSA < 0.6 m<sup>2</sup>: 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 149: Line 144:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''5-day course, followed by:'''
 
'''5-day course, followed by:'''
 
+
</div></div><br>
====Chemotherapy, Intensification II====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Intensification, part II===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
*High Dose [[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4  
 
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4  
Line 161: Line 157:
 
**BSA < 0.6 m<sup>2</sup>: 0.4 mg/kg once per day on days 3 to 6
 
**BSA < 0.6 m<sup>2</sup>: 0.4 mg/kg once per day on days 3 to 6
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Intensification I
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Intensification I
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 183: Line 175:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''6-day course'''
 
'''6-day course'''
 
+
</div></div>
 
===References===
 
===References===
 
# '''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):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
 
# '''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):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
  
 
==COG AAML1031 arm A (high-risk)==
 
==COG AAML1031 arm A (high-risk)==
===Protocol===
+
<div class="toccolours" style="background-color:#eeeeee">
====Chemotherapy, induction I====
+
===Induction, part I===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10  
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
Line 199: Line 191:
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1  
 
*[[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)
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 221: Line 210:
 
|70
 
|70
 
|}
 
|}
 
+
'''10-day course, followed by:'''
 
+
</div></div><br>
'''10-day course'''
+
<div class="toccolours" style="background-color:#eeeeee">
 
+
===Induction, part II===
====Chemotherapy, induction II====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4  
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
Line 231: Line 221:
 
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6.  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6.  
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction I
 
*[[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)
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 253: Line 240:
 
|70
 
|70
 
|}
 
|}
 
+
'''6-day course, followed by:'''
 
+
</div></div><br>
'''6-day course'''
+
<div class="toccolours" style="background-color:#eeeeee">
 
+
===Intensification, part I===
====Chemotherapy, intensification I====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5  
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 283: Line 268:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''5-day course'''
 
'''5-day course'''
 
+
</div></div><br>
====Chemotherapy, intensification II====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Intensification, part II===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 2, 8, 9
 
*High Dose [[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 2, 8, 9
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 100 mg/kg IV over 3 hours every 12 hours on days 1, 2, 8, 9
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 100 mg/kg IV over 3 hours every 12 hours on days 1, 2, 8, 9
*[[E.Coli L-Asparaginase (LASP)]] 6000 international units/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
*[[E.Coli L-Asparaginase (LASP)]] 6000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
**IF BSA < 0.6 m<sup>2</sup>, [[E.Coli L-Asparaginase (LASP)]] 200 international units/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
**IF BSA < 0.6 m<sup>2</sup>, [[E.Coli L-Asparaginase (LASP)]] 200 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
  may substitute with another asparaginase formulation
 
  may substitute with another asparaginase formulation
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 25,000 International units/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 25,000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
**IF BSA < 0.6 m<sup>2</sup>, [[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 830 international units/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
**IF BSA < 0.6 m<sup>2</sup>, [[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 830 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
  If Erwinia asparaginase is not available, pegasparaginase should NOT be given, and asparaginase should be omitted
 
  If Erwinia asparaginase is not available, pegasparaginase should NOT be given, and asparaginase should be omitted
 
 
'''28-day course'''
 
'''28-day course'''
 
+
</div></div>
 
===References===
 
===References===
 
# '''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):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
 
# '''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):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
  
 
==COG AAML1031 arm C (FLT3/ITD+)==
 
==COG AAML1031 arm C (FLT3/ITD+)==
===Protocol===
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Induction, part I===
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*FLT3/ITD+
 
*FLT3/ITD+
====Chemotherapy, induction I====
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10  
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
Line 313: Line 302:
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 +
====Targeted therapy====
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 11 to 28
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 11 to 28
 
**see [[Sorafenib Dosing Nomogram]] for more details.
 
**see [[Sorafenib Dosing Nomogram]] for more details.
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1  
 
*[[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)
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
**
 
**
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 337: Line 325:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''28-day course'''
 
'''28-day course'''
 
+
</div></div><br>
====Chemotherapy, induction II====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Induction, part II===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 8  
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 8  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 8
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 8
Line 348: Line 337:
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 +
====Targeted therapy====
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 9 to 36
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 9 to 36
 
**see [[Sorafenib Dosing Nomogram]] for more details.
 
**see [[Sorafenib Dosing Nomogram]] for more details.
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
*[[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).  
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).  
 
**
 
**
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 372: Line 360:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''36-day course'''
 
'''36-day course'''
 
+
</div></div><br>
====Chemotherapy, intensification I====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Intensification, part I===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5  
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 +
====Targeted therapy====
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 6 through 33
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 6 through 33
 
**see [[Sorafenib Dosing Nomogram]] for more details.
 
**see [[Sorafenib Dosing Nomogram]] for more details.
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II.  
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II.  
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 404: Line 391:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''33-day course'''
 
'''33-day course'''
 
+
</div></div><br>
====Chemotherapy, intensification II====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Intensification, part II===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4  
 
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
Line 414: Line 402:
 
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6
 
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions  
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions  
 +
====Targeted therapy====
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 7 to 34  
 
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 7 to 34  
 
**see [[Sorafenib Dosing Nomogram]] for more details
 
**see [[Sorafenib Dosing Nomogram]] for more details
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Intensification I
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Intensification I
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 437: Line 423:
 
|70
 
|70
 
|}
 
|}
 
 
 
'''6-day course'''
 
'''6-day course'''
 
+
</div></div>
 
===References===
 
===References===
 
# '''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):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
 
# '''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):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
  
 
==COG AAML0531 arm B (Gemtuzumab)==
 
==COG AAML0531 arm B (Gemtuzumab)==
===Protocol===
+
<div class="toccolours" style="background-color:#eeeeee">
====Chemotherapy, induction I====
+
===Induction, part I===
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 15 minutes every 12 hours on days 1 to 10  
+
<div class="toccolours" style="background-color:#b3e2cd">
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 10
+
====Chemotherapy====
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 6 hours once per day on days 1, 3, 5  
+
*[[Cytarabine (Ara-C)]] by the following weight-based criteria:
**IF BSA < 0.6 m<sup>2</sup>, [[Daunorubicin (Cerubidine)]] 1.67 mg/kg IV over 6 hours once per day on days 1, 3, 5
+
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 15 minutes every 12 hours on days 1 to 10  
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5  
+
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 10
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 4 hours once per day on days 1 to 5
+
*[[Daunorubicin (Cerubidine)]] by the following weight-based criteria:
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV over 2 hours once on day 6
+
**BSA 0.6 m<sup>2</sup> or more: 50 mg/m<sup>2</sup> IV over 6 hours once per day on days 1, 3, 5  
**IF BSA < 0.6 m<sup>2</sup>, [[Gemtuzumab ozogamicin (Mylotarg)]] 0.1 mg/kg once on day 6
+
**BSA < 0.6 m<sup>2</sup>: 1.67 mg/kg IV over 6 hours once per day on days 1, 3, 5
 +
*[[Etoposide (Vepesid)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5  
 +
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 4 hours once per day on days 1 to 5
 +
====Antibody-drug conjugate therapy====
 +
*[[Gemtuzumab ozogamicin (Mylotarg)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 3 mg/m<sup>2</sup> IV over 2 hours once on day 6
 +
**BSA < 0.6 m<sup>2</sup>: 0.1 mg/kg IV once on day 6
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1  
 
*[[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)
 
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 476: Line 465:
 
|70
 
|70
 
|}
 
|}
 
 
'''10-day course'''
 
'''10-day course'''
 
+
</div></div><br>
====Chemotherapy, induction II====
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Induction, part II===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 15 minutes every 12 hours on days 1 to 8  
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 15 minutes every 12 hours on days 1 to 8  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 8
 
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 8
Line 486: Line 477:
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5  
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5  
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 4 hours once per day on days 1 to 5
 
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 4 hours once per day on days 1 to 5
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 507: Line 495:
 
|70
 
|70
 
|}
 
|}
 
 
'''28-day course'''
 
'''28-day course'''
 
+
</div></div><br>
====Chemotherapy, intensification I====
+
<div class="toccolours" style="background-color:#eeeeee">
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 hour every 12 hours on days 1 to 5
+
===Intensification, part I===
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 hour every 12 hours on days 1 to 5
+
<div class="toccolours" style="background-color:#b3e2cd">
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 5  
+
====Chemotherapy====
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 4 hours once per day on days 1 to 5
+
*High Dose [[Cytarabine (Ara-C)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 hour every 12 hours on days 1 to 5
 +
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 hour every 12 hours on days 1 to 5
 +
*[[Etoposide (Vepesid)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 150 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 5  
 +
**BSA < 0.6 m<sup>2</sup>: 5 mg/kg IV over 4 hours once per day on days 1 to 5
 
**Each dose of [[Etoposide (Vepesid)]] should immediately follow the AM dose of [[Cytarabine (Ara-C)]]
 
**Each dose of [[Etoposide (Vepesid)]] should immediately follow the AM dose of [[Cytarabine (Ara-C)]]
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction II
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction II
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 537: Line 526:
 
|70
 
|70
 
|}
 
|}
 
 
'''5-day course'''
 
'''5-day course'''
 
+
</div></div><br>
====Chemotherapy, intensification II====
+
<div class="toccolours" style="background-color:#eeeeee">
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 hour every 12 hours on days 1 to 4
+
===Intensification, part II===
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 hour every 12 hours on days 1 to 4
+
<div class="toccolours" style="background-color:#b3e2cd">
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV over 1 hour once per day on days 3 to 6  
+
====Chemotherapy====
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6
+
*High Dose [[Cytarabine (Ara-C)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 hour every 12 hours on days 1 to 4
 +
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 hour every 12 hours on days 1 to 4
 +
*[[Mitoxantrone (Novantrone)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 12 mg/m<sup>2</sup> IV over 1 hour once per day on days 3 to 6  
 +
**BSA < 0.6 m<sup>2</sup>: 0.4 mg/kg once per day on days 3 to 6
 
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
**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/m<sup>2</sup> IV over 2 hours once on day 7
+
====Antibody-drug conjugate therapy====
**IF BSA < 0.6 m<sup>2</sup>, [[Gemtuzumab ozogamicin (Mylotarg)]] 0.1 mg/kg once on day 7
+
*[[Gemtuzumab ozogamicin (Mylotarg)]] by the following weight-based criteria:
 
+
**BSA 0.6 m<sup>2</sup> or more: 3 mg/m<sup>2</sup> IV over 2 hours once on day 7
 +
**BSA < 0.6 m<sup>2</sup>: 0.1 mg/kg once on day 7
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Intensification I
 
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Intensification I
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 569: Line 561:
 
|70
 
|70
 
|}
 
|}
 
 
'''7-day course'''
 
'''7-day course'''
 
+
</div></div><br>
====Chemotherapy, intensification III====
+
<div class="toccolours" style="background-color:#eeeeee">
*High Dose [[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 2, 8, 9
+
===Intensification, part III===
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 hour every 12 hours on days 1, 2, 8, 9
+
<div class="toccolours" style="background-color:#b3e2cd">
*[[E.Coli L-Asparaginase (LASP)]] 6000 international units/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
====Chemotherapy====
**IF BSA < 0.6 m<sup>2</sup>, [[E.Coli L-Asparaginase (LASP)]] 200 international units/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
*High Dose [[Cytarabine (Ara-C)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 2, 8, 9
 +
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 hour every 12 hours on days 1, 2, 8, 9
 +
*[[E.Coli L-Asparaginase (LASP)]] by the following weight-based criteria:
 +
**BSA 0.6 m<sup>2</sup> or more: 6000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 +
**BSA < 0.6 m<sup>2</sup>: 200 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
  may substitute with another asparaginase formulation
 
  may substitute with another asparaginase formulation
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 25,000 International units/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] by the following weight-based criteria:
**IF BSA < 0.6 m<sup>2</sup>, [[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 830 international units/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
+
**BSA 0.6 m<sup>2</sup> or more: 25,000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
+
**BSA < 0.6 m<sup>2</sup>: 830 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
'''28-day course'''
 
'''28-day course'''
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
#'''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. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
  
 
==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}==
 
==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}==
 
 
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
<br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
<br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
<br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
<br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
<br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
<br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #1, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}===
 
===Regimen variant #1, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 621: Line 616:
 
|}
 
|}
 
''Note: these trials have complicated treatment schemas; see papers for details. This is IND2 for COG AAML0531.''
 
''Note: these trials have complicated treatment schemas; see papers for details. This is IND2 for COG AAML0531.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
 
 
*UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction
 
*UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction
 
*COG AAML0531: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction versus [[#ADE_.26_GO|ADE & GO]]
 
*COG AAML0531: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction versus [[#ADE_.26_GO|ADE & GO]]
 
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 8
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 8
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
 
'''8-day course'''
 
'''8-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*UK MRC AML10: [[#MACE_88|MACE]] consolidation
 
*UK MRC AML10: [[#MACE_88|MACE]] consolidation
 
*COG AAML0531: [[#CYVE|CYVE]] interim maintenance
 
*COG AAML0531: [[#CYVE|CYVE]] interim maintenance
 
*Other trials: Consolidation (see paper for details)
 
*Other trials: Consolidation (see paper for details)
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}===
 
===Regimen variant #2, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 673: Line 669:
 
|}
 
|}
 
''Note: these trials have complicated treatment schemas; see papers for details.''
 
''Note: these trials have complicated treatment schemas; see papers for details.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 or days 2, 4, 6
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 or days 2, 4, 6
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 or days 2 to 6
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 or days 2 to 6
 
 
'''10-day course'''
 
'''10-day course'''
 
+
</div></div>
 
===References===
 
===References===
 
#'''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. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed]
 
#'''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. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed]
Line 689: Line 684:
 
##'''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. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
##'''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. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
#'''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. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
#'''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. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
 
==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}==
 
==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}==
 
 
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
<br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
<br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
<br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
<br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:386dha|Variant=1}}===
 
===Regimen {{#subobject:386dha|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 711: Line 705:
 
|}
 
|}
 
''Note: this regimen was intended for patients younger than 22 years.''
 
''Note: this regimen was intended for patients younger than 22 years.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 2, 4, 6
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 2, 4, 6
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
 
'''6-day course'''
 
'''6-day course'''
 
+
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*Response- and risk-adapted therapy; see paper for details
 
*Response- and risk-adapted therapy; see paper for details
 +
</div></div>
 
===References===
 
===References===
 
#'''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. [https://doi.org/10.1200/jco.19.00327 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7001777/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31246522 PubMed] NCT00703820
 
#'''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. [https://doi.org/10.1200/jco.19.00327 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7001777/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31246522 PubMed] NCT00703820
 
 
==ADE & GO {{#subobject:e33id7|Regimen=1}}==
 
==ADE & GO {{#subobject:e33id7|Regimen=1}}==
 
 
ADE & GO: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposidem, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
ADE & GO: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposidem, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:99ye46|Variant=1}}===
 
===Regimen {{#subobject:99ye46|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 743: Line 736:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
 
====Antibody-drug conjugate therapy====
 
====Antibody-drug conjugate therapy====
 
 
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV over 2 hours once on day 6
 
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV over 2 hours once on day 6
 
 
'''10-day course'''
 
'''10-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction
 
*[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
#'''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. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
 
==AIE {{#subobject:948b49|Regimen=1}}==
 
==AIE {{#subobject:948b49|Regimen=1}}==
 
 
AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide
 
AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide
 
<br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
 
<br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:c7b35a|Variant=1}}===
 
===Regimen {{#subobject:c7b35a|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 781: Line 770:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
 
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
 
'''7-day course'''
 
'''7-day course'''
 +
</div></div>
 
===References===
 
===References===
 
#'''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; [[Study_Groups#EORTC|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. [https://www.nature.com/articles/2403932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16136166 PubMed] NCT00002517
 
#'''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; [[Study_Groups#EORTC|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. [https://www.nature.com/articles/2403932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16136166 PubMed] NCT00002517
 
 
==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}==
 
==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}==
 
 
DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
 
DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}===
 
===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 810: Line 798:
 
|}
 
|}
 
''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|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.''
 
''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|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.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
 
'''10-day course'''
 
'''10-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*See papers for details (to be completed).
 
*See papers for details (to be completed).
 
+
</div></div>
 
===References===
 
===References===
 
#'''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. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
#'''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. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
## '''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. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
## '''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. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
##'''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. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
##'''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. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
 
==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}==
 
==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}==
 
 
DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:6a938e|Variant=1}}===
 
===Regimen {{#subobject:6a938e|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 843: Line 830:
 
|-
 
|-
 
|}
 
|}
''This trial has complicated treatment schemas; see papers for details.''
+
''Note: This trial has complicated treatment schemas; see papers for details.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
 
====Antibody-drug conjugate therapy====
 
====Antibody-drug conjugate therapy====
 
 
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 
 
'''10-day course'''
 
'''10-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*See paper for details (to be completed).
 
*See paper for details (to be completed).
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
#'''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. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
## '''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. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
## '''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. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
Line 865: Line 849:
  
 
==FLAG-Ida {{#subobject:7fc219|Regimen=1}}==
 
==FLAG-Ida {{#subobject:7fc219|Regimen=1}}==
 
 
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin
 
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:44e85e|Variant=1}}===
 
===Regimen {{#subobject:44e85e|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 883: Line 867:
 
|}
 
|}
 
''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.''
 
''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, '''given 4 hours after fludarabine'''
 
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, '''given 4 hours after fludarabine'''
 
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6
 
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6
 
 
====Growth factor therapy====
 
====Growth factor therapy====
 
 
*[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7
 
*[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7
 
 
'''7-day course'''
 
'''7-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*See paper for details
 
*See paper for details
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
#'''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. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
## '''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. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
## '''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. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
##'''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. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
##'''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. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
 
=Consolidation after upfront therapy=
 
=Consolidation after upfront therapy=
 
==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}==
 
==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}==
 
 
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
 
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:5d4efb|Variant=1}}===
 
===Regimen {{#subobject:5d4efb|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 923: Line 903:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
 
 
*[[#7.2B3d_.28standard-dose.29|7+3d]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]]
 
*[[#7.2B3d_.28standard-dose.29|7+3d]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]]
 
{{#lst:Autologous HSCT|5d4efb}}
 
{{#lst:Autologous HSCT|5d4efb}}
 +
</div></div>
 
===References===
 
===References===
 
 
#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. [https://doi.org/10.1056/NEJM199605303342203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8618581 PubMed]
 
#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. [https://doi.org/10.1056/NEJM199605303342203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8618581 PubMed]
 
 
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}==
 
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}==
 
 
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:6ca28d|Variant=1}}===
 
===Regimen {{#subobject:6ca28d|Variant=1}}===
 
{| class="wikitable sortable" style="width: 40%; text-align:center;"
 
{| class="wikitable sortable" style="width: 40%; text-align:center;"
Line 944: Line 923:
 
|}
 
|}
 
{{#lst:Allogeneic HSCT|6ca28d}}
 
{{#lst:Allogeneic HSCT|6ca28d}}
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
 
*[[Allogeneic stem cells]]
 
*[[Allogeneic stem cells]]
 
 
'''Stem cells transfused on day 0'''
 
'''Stem cells transfused on day 0'''
 +
</div></div>
 
===References===
 
===References===
 
#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. [https://doi.org/10.1056/NEJM198712243172602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3317056 PubMed]
 
#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. [https://doi.org/10.1056/NEJM198712243172602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3317056 PubMed]
 
 
=Relapsed or refractory, salvage therapy=
 
=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.''
 
''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.''
 
 
==COGAAML1421 protocol==
 
==COGAAML1421 protocol==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Protocol===
 
===Protocol===
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy, cycle 1====
 
====Chemotherapy, cycle 1====
*[[Cytarabine and Daunorubicin Liposome (CPX-351)]] 135 units/m<sup>2</sup> IV over 90 minutes on days 1, 3, 5  
+
*[[Cytarabine and daunorubicin liposomal (Vyxeos)]] 135 units/m<sup>2</sup> IV over 90 minutes on days 1, 3, 5  
 
====CNS therapy====
 
====CNS therapy====
 
*[[Cytarabine (Ara-C)]] IT 2 doses
 
*[[Cytarabine (Ara-C)]] IT 2 doses
Line 965: Line 945:
 
*CNS2 Patients
 
*CNS2 Patients
 
**[[Cytarabine (Ara-C)]] IT twice weekly until the CSF is clear starting at least 48 hours following the 3rd dose of CPX-351
 
**[[Cytarabine (Ara-C)]] IT twice weekly until the CSF is clear starting at least 48 hours following the 3rd dose of CPX-351
 
 
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
! style="width: 25%" |Age
 
! style="width: 25%" |Age
Line 979: Line 957:
 
|70
 
|70
 
|}
 
|}
 
 
'''28-Day course'''
 
'''28-Day course'''
 
 
====Chemotherapy, cycle 2====
 
====Chemotherapy, cycle 2====
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SQ once per day on days 1 to 5, one hour prior to each dose of [[Fludarabine (Fludara)]]
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SQ once per day on days 1 to 5, one hour prior to each dose of [[Fludarabine (Fludara)]]
Line 989: Line 965:
 
*High Dose [[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 1 to 3 hours every once daily on days 1 to 5
 
*High Dose [[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 1 to 3 hours every once daily on days 1 to 5
 
**Begin [[Cytarabine (Ara-C)]] 4 hours after the start of [[Fludarabine (Fludara)]]
 
**Begin [[Cytarabine (Ara-C)]] 4 hours after the start of [[Fludarabine (Fludara)]]
 
 
'''28-day course'''
 
'''28-day course'''
 
+
</div></div>
 
===References===
 
===References===
 
# '''COG AAML1421:'''Cooper TM, Absalon M, Alonzo TA, Gerbing RB, Leger KJ, Hirsch BA, Pollard JA, Razzouk BI, Aplenc R, Kolb EA. AAML1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A report from the Children's Oncology Group. Journal of Clinical Oncology. 2019 May;37(15). [https://doi.org/10.1200/JCO.2019.37.15_suppl.10003 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32401633/ PubMed]NCT02642965
 
# '''COG AAML1421:'''Cooper TM, Absalon M, Alonzo TA, Gerbing RB, Leger KJ, Hirsch BA, Pollard JA, Razzouk BI, Aplenc R, Kolb EA. AAML1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A report from the Children's Oncology Group. Journal of Clinical Oncology. 2019 May;37(15). [https://doi.org/10.1200/JCO.2019.37.15_suppl.10003 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32401633/ PubMed]NCT02642965
  
 
==FLAG {{#subobject:551761|Regimen=1}}==
 
==FLAG {{#subobject:551761|Regimen=1}}==
 
 
FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
 
FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:bdc7e4|Variant=1}}===
 
===Regimen {{#subobject:bdc7e4|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
Line 1,014: Line 989:
 
|}
 
|}
 
''Note: this regimen was studied in patients up to 21 years of age.''
 
''Note: this regimen was studied in patients up to 21 years of age.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
 
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
 
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given third, 4 hours after the start of fludarabine'''
 
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given third, 4 hours after the start of fludarabine'''
 
 
====Growth factor therapy====
 
====Growth factor therapy====
 
 
*[[Filgrastim (Neupogen)]] 200 mcg/m<sup>2</sup> (route not specified) once per day on days 0 to 5, '''given first'''
 
*[[Filgrastim (Neupogen)]] 200 mcg/m<sup>2</sup> (route not specified) once per day on days 0 to 5, '''given first'''
 
 
'''2 cycles (length not specified)'''
 
'''2 cycles (length not specified)'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[Regimen_classes#Allogeneic_HSCT|allogeneic HSCT]]
 
*[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[Regimen_classes#Allogeneic_HSCT|allogeneic HSCT]]
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
#'''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. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
 
=Consolidation after salvage therapy=
 
=Consolidation after salvage therapy=
 
==Cytarabine & Thioguanine {{#subobject:3c38bc|Regimen=1}}==
 
==Cytarabine & Thioguanine {{#subobject:3c38bc|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:f2728e|Variant=1}}===
 
===Regimen {{#subobject:f2728e|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 1,045: Line 1,016:
 
|}
 
|}
 
''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".''
 
''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".''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
 
 
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 4
 
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 4
 
*[[Thioguanine (Tabloid)]] as follows:
 
*[[Thioguanine (Tabloid)]] as follows:
 
**Cycles 1 & 2: 100 mg/m<sup>2</sup> PO once per day
 
**Cycles 1 & 2: 100 mg/m<sup>2</sup> PO once per day
 
 
'''14-day cycles'''
 
'''14-day cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic HSCT]]
 
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic HSCT]]
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
#'''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. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
 
==CYVE {{#subobject:4bd791|Regimen=1}}==
 
==CYVE {{#subobject:4bd791|Regimen=1}}==
 
 
CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
 
CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:a16529|Variant=1}}===
 
===Regimen {{#subobject:a16529|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 1,077: Line 1,046:
 
|}
 
|}
 
''Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.''
 
''Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
 
 
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
 
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m<sup>2</sup>)
 
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m<sup>2</sup>)
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV twice per day on days 1 to 4
 
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV twice per day on days 1 to 4
 
+
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
 
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic HSCT]]
 
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic HSCT]]
 
+
</div></div>
 
===References===
 
===References===
 
 
#'''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. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
#'''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. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
 
[[Category:Acute myeloid leukemia regimens]]
 
[[Category:Acute myeloid leukemia regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Acute leukemias]]
 
[[Category:Acute leukemias]]
 
[[Category:Pediatric hematologic neoplasms]]
 
[[Category:Pediatric hematologic neoplasms]]

Revision as of 01:29, 23 October 2022

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

The following study protocols are included on this page:

Study Years of enrollment
UK MRC AML10 1988-1995
EORTC 58921 1992-2002
I-BFM-SG 2001/01 2001-2009
UK MRC AML15 2002-2006
St. Jude AML02 2002-2008
COG AAML0531 2006-2010
St. Jude AML08 2008-2017
COG AAML1031 2011-2016
COG AAML1421 2016-2018


Guidelines

"How I Treat"

Upfront induction therapy

COG AAML1031 arm A (low-risk)

Induction, part I

Chemotherapy

CNS therapy, 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, followed by:


Induction, part II

Chemotherapy

  • Cytarabine (Ara-C) by the following BSA-based criteria:
    • BSA 0.6 m2 or more: 100 mg/m2 IV over 1 to 30 minutes every 12 hours on days 1 to 8
    • BSA < 0.6 m2: 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 8
  • Daunorubicin (Cerubidine) by the following BSA-based criteria:
    • BSA 0.6 m2 or more: 50 mg/m2 IV over 1 to 15 minutes once per day on days 1, 3, 5
    • BSA < 0.6 m2: 1.7 mg/kg IV over 1 to 15 minutes once per day on days 1, 3, 5
  • Etoposide (Vepesid) by the following BSA-based criteria:
    • BSA 0.6 m2 or more: 100 mg/m2 IV over 60 to 120 minutes once per day on days 1 to 5
    • BSA < 0.6 m2: 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5

CNS therapy, 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, followed by:


Intensification, part I

Chemotherapy

  • High Dose Cytarabine (Ara-C) by the following BSA-based criteria:
    • BSA 0.6 m2 or more: 1000 mg/m2 IV over 1 to 3 hours every 12 hours on days 1 to 5
    • BSA < 0.6 m2: 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
  • Etoposide (Vepesid) by the following BSA-based criteria:
    • BSA 0.6 m2 or more: 150 mg/m2 IV over 60 to 120 minutes once per day on days 1 through 5
    • BSA < 0.6 m2: 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5

CNS therapy, 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, followed by:


Intensification, part II

Chemotherapy

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

CNS therapy, 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):1879-1886. Epub 2020 Feb 6. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01371981

COG AAML1031 arm A (high-risk)

Induction, part I

Chemotherapy

CNS therapy, 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, followed by:


Induction, part II

Chemotherapy

CNS therapy, 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, followed by:


Intensification, part I

Chemotherapy

CNS therapy, 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


Intensification, part II

Chemotherapy

  • High Dose Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 2, 8, 9
    • IF BSA < 0.6 m2, Cytarabine (Ara-C) 100 mg/kg IV over 3 hours every 12 hours on days 1, 2, 8, 9
  • E.Coli L-Asparaginase (LASP) 6000 IU/m2 IM on Day 2 (at hour 42), 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 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
may substitute with another asparaginase formulation
If Erwinia asparaginase is not available, pegasparaginase should NOT be given, and asparaginase should be omitted

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):1879-1886. Epub 2020 Feb 6. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01371981

COG AAML1031 arm C (FLT3/ITD+)

Induction, part I

Biomarker eligibility criteria

  • FLT3/ITD+

Chemotherapy

Targeted therapy

CNS therapy, 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


Induction, part II

Chemotherapy

Targeted therapy

CNS therapy, 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


Intensification, part I

Chemotherapy

Targeted therapy

CNS therapy, 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


Intensification, part II

Chemotherapy

Targeted therapy

CNS therapy, 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):1879-1886. Epub 2020 Feb 6. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01371981

COG AAML0531 arm B (Gemtuzumab)

Induction, part I

Chemotherapy

  • Cytarabine (Ara-C) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 100 mg/m2 IV over 15 minutes every 12 hours on days 1 to 10
    • BSA < 0.6 m2: 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 10
  • Daunorubicin (Cerubidine) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 50 mg/m2 IV over 6 hours once per day on days 1, 3, 5
    • BSA < 0.6 m2: 1.67 mg/kg IV over 6 hours once per day on days 1, 3, 5
  • Etoposide (Vepesid) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 100 mg/m2 IV over 4 hours once per day on days 1 to 5
    • BSA < 0.6 m2: 3.3 mg/kg IV over 4 hours once per day on days 1 to 5

Antibody-drug conjugate therapy

  • Gemtuzumab ozogamicin (Mylotarg) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 3 mg/m2 IV over 2 hours once on day 6
    • BSA < 0.6 m2: 0.1 mg/kg IV once on day 6

CNS therapy, 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


Induction, part II

Chemotherapy

CNS therapy, prophylaxis

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

28-day course


Intensification, part I

Chemotherapy

  • High Dose Cytarabine (Ara-C) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 1000 mg/m2 IV over 1 hour every 12 hours on days 1 to 5
    • BSA < 0.6 m2: 33 mg/kg IV over 1 hour every 12 hours on days 1 to 5
  • Etoposide (Vepesid) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 150 mg/m2 IV over 1 hour once per day on days 1 to 5
    • BSA < 0.6 m2: 5 mg/kg IV over 4 hours once per day on days 1 to 5
    • Each dose of Etoposide (Vepesid) should immediately follow the AM dose of Cytarabine (Ara-C)

CNS therapy, prophylaxis

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

5-day course


Intensification, part II

Chemotherapy

  • High Dose Cytarabine (Ara-C) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 1000 mg/m2 IV over 1 hour every 12 hours on days 1 to 4
    • BSA < 0.6 m2: 33 mg/kg IV over 1 hour every 12 hours on days 1 to 4
  • Mitoxantrone (Novantrone) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 12 mg/m2 IV over 1 hour once per day on days 3 to 6
    • BSA < 0.6 m2: 0.4 mg/kg once per day on days 3 to 6
    • On days where both are given, give Mitoxantrone (Novantrone) 8 hours AFTER the END of the high dose Cytarabine (Ara-C) infusions

Antibody-drug conjugate therapy

  • Gemtuzumab ozogamicin (Mylotarg) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 3 mg/m2 IV over 2 hours once on day 7
    • BSA < 0.6 m2: 0.1 mg/kg once on day 7

CNS therapy, 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


Intensification, part III

Chemotherapy

  • High Dose Cytarabine (Ara-C) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 2, 8, 9
    • BSA < 0.6 m2: 33 mg/kg IV over 1 hour every 12 hours on days 1, 2, 8, 9
  • E.Coli L-Asparaginase (LASP) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 6000 IU/m2 IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
    • BSA < 0.6 m2: 200 IU/kg IM on Day 2 (at hour 42), 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) by the following weight-based criteria:
    • BSA 0.6 m2 or more: 25,000 IU/m2 IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
    • BSA < 0.6 m2: 830 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)

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 dosing details in manuscript PubMed NCT00372593

ADE (standard-dose Ara-C)

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 3 (E-switch-ic) DAT 3+8 Did not meet efficacy endpoints
Burnett et al. 2010 (UK MRC AML15) 2002-2006 Phase 3 (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

Chemotherapy

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 3 (E-switch-ic) DAT 3+10 Did not meet efficacy endpoints
Burnett et al. 2010 (UK MRC AML15) 2002-2006 Phase 3 (C) See link See link
Rubnitz et al. 2010 (AML02) 2002-2008 Phase 3 (C) ADE; high-dose Ara-C Did not meet primary endpoint of MRD-positivity at day 22
Gamis et al. 2014 (COG AAML0531) 2006-2010 Phase 3 (C) ADE & GO Seems to have inferior EFS

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

Chemotherapy

10-day course

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 dosing details in manuscript 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. AML02: Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010 Jun;11(6):543-52. Epub 2010 May 5. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00136084
  3. 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
  4. 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 dosing details in manuscript PubMed NCT00372593

ADE (high-dose Ara-C)

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 3 (C) Clofarabine & Cytarabine Seems to have superior MRD at day 22

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

Chemotherapy

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 dosing details in manuscript PubMed NCT00703820

ADE & GO

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 3 (E-RT-esc) ADE 10-3-5 Seems to have superior EFS

Chemotherapy

Antibody-drug conjugate therapy

10-day course

Subsequent treatment

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 dosing details in manuscript PubMed NCT00372593

AIE

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 3 (C) MEC Did not meet efficacy endpoints

Chemotherapy

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

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 3 (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

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

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 3 (E-esc) See link See link

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

Chemotherapy

Antibody-drug conjugate therapy

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

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 3 (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

Growth factor therapy

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

BuCy: Busulfan & Cyclophosphamide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ravindranath et al. 1996 1988-1993 Phase 3 (E-esc) Intensive chemotherapy Did not meet primary endpoint of EFS24

Preceding treatment

Chemotherapy

Supportive therapy

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 dosing details in manuscript PubMed

Cyclophosphamide & TBI, then allo HSCT

Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study Evidence
Brochstein et al. 1987 Non-randomized

Details in most of the manuscripts are limited.

Chemotherapy

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

One course

Immunotherapy

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.

COGAAML1421 protocol

Protocol

Chemotherapy, cycle 1

CNS therapy

  • Cytarabine (Ara-C) IT 2 doses
    • At the time of diagnostic lumbar puncture or Day 0 of cycle 1
    • At the time of the Day 28 to 30 bone marrow biopsy, or up to one week prior to Day 1 of cycle 2
  • CNS2 Patients
    • Cytarabine (Ara-C) IT twice weekly until the CSF is clear starting at least 48 hours following the 3rd dose of CPX-351
Age Dose 1 - 1.99 30
2 - 2.99 50
≥ 3 70

28-Day course

Chemotherapy, cycle 2

Pegfilgrastim cannot be utilized in the place of filgrastim or biosimilar

28-day course

References

  1. COG AAML1421:Cooper TM, Absalon M, Alonzo TA, Gerbing RB, Leger KJ, Hirsch BA, Pollard JA, Razzouk BI, Aplenc R, Kolb EA. AAML1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A report from the Children's Oncology Group. Journal of Clinical Oncology. 2019 May;37(15). link to original article contains dosing details in manuscript link to PMC article PubMedNCT02642965

FLAG

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 3 (C) FLAG-DNX Seems to have inferior CR rate

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

Chemotherapy

Growth factor therapy

2 cycles (length not specified)

Subsequent treatment

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 dosing details in manuscript PubMed NCT00186966

Consolidation after salvage therapy

Cytarabine & Thioguanine

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

Chemotherapy

14-day cycles

Subsequent treatment

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 dosing details in manuscript PubMed NCT00186966

CYVE

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

Chemotherapy

Subsequent treatment

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 dosing details in manuscript PubMed NCT00186966