Section editor transclusionsThis page contains studies that are specific to pediatric populations. For the more general B-cell acute lymphoblastic leukemia page, including regimens for adolescents and young adults, follow this link.
CNS2 Patients will receive an additional dose of Cytarabine (Ara-C) IT on either day 4, 5, or 6, followed by Methotrexate (MTX) IT on day 8 and then another dose of Cytarabine (Ara-C) IT on either day 11 or 12 according to the following dosing.
Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
Given over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted).
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
Given over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted).
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I
References
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
Currently maintenance arm B and D are also treated with Methotrexate (MTX) PO at 20 mg/m2 (decreased from the starting dose of 40 mg/m2) on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57
Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 to 5, 29 - 33, and 57 - 61 (6 mg/m2/day)
12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I
References
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I
References
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
Given as a 200 mg/m2 bolus over 20 - 30 minutes followed by 800 mg/m2 over 23.5 hours (initial bolus of 30 minutes) or 23 hours and 40 minutes (if initial bolus was over 20 minutes)
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 78, and 85.
Dexamethasone (Decadron) 3 mg/m2/dose IV or PO twice daily on days 15 - 21, and 78 - 84. (6 mg/m2/day)
Folinic acid (Leucovorin) 10 mg/m2 x 2 doses PO or IV (given 48 and 60 hours after the START of MTX infusion, continuing until MTX level < 0.2 μM) on days 9 - 10, 30 - 31, 51 - 52, 72 - 73, 93 - 94, and 114 - 115.
CNS prophylaxis
Methotrexate (MTX) IT once on day 8, 29, 50, 71, 92, and 113 (To be delivered within 6 hours of the beginning of the IV MTX infusion, -6hr to + 6 hr)
Age
Dose
1 - 1.99
8 mg
2 - 2.99
10 mg
3 - 8.99
12 mg
≥ 9
15 mg
19-week cycle
References
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
16-week cycles until a total duration of therapy of 2.5 years from the date of diagnosis is reached for both boys and girls.
References
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I
References
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.
CNS2 Patients will receive an additional dose of Cytarabine (Ara-C) IT on either day 4, 5, or 6, and then another dose of Cytarabine (Ara-C) IT on either day 11 or 12 according to the following dosing.
Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
Age 9 and older: 15 mg IT once per day on days 8 & 29
4-week course
Subsequent treatment
See protocol for details of treatment beyond induction
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
High Dose Methotrexate (MTX) 5000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
MTX 500 mg/m2 IV infused over 30 minutes. This is followed, immediately, by MTX 4500 mg/m2 given by continuous IV infusion over 23.5 hours.
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX
Folinic acid (Leucovorin) 15 mg/m2 x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 - 4, 17 - 18, 31 - 32, and 45 - 46.
When IT therapy and HD MTX are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV MTX infusion. (hour -6 or +6, with 0 being the start of the MTX bolus).
63-Day Course
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Methotrexate (MTX) IT once per day on days 1, 8, 15, and 22. (Omit days 15 and 22 for CNS3 Patients)
Age
Dose
1 - 1.99
8 mg
2 - 2.99
10 mg
3 - 8.99
12 mg
≥ 9
15 mg
56-Day course
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
High Dose Methotrexate (MTX) 5000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
MTX 500 mg/m2 IV infused over 30 minutes. This is followed, immediately, by MTX 4500 mg/m2 given by continuous IV infusion over 23.5 hours.
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX
Folinic acid (Leucovorin) 15 mg/m2 x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 - 4, 17 - 18, 31 - 32, and 45 - 46.
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, and 41.
Methotrexate (MTX) 100 mg/m2 IV over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted) on days 1, 150 mg/m2 on day 11, 200 mg/m2 on day 21, 250 mg/m2 on day 31, and 300 mg/m2 on day 41.
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Total body irradiation (TBI) 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance.
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.
Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).
Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.
CNS prophylaxis
Methotrexate (MTX) IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation).
Age
Dose
1 - 1.99
8 mg
2 - 2.99
10 mg
3 - 8.99
12 mg
≥ 9
15 mg
12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.
56-Day Course
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
High Dose Methotrexate (MTX) 5000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
MTX 500 mg/m2 IV infused over 30 minutes. This is followed, immediately, by MTX 4500 mg/m2 given by continuous IV infusion over 23.5 hours.
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX
Folinic acid (Leucovorin) 15 mg/m2 x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 - 4, 17 - 18, 31 - 32, and 45 - 46.
Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 63.
When IT therapy and HD MTX are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV MTX infusion. (hour -6 or +6, with 0 being the start of the MTX bolus).
63-Day Course
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original article
Interim Maintenance II with Capizzi MTX (Dasatinib Arm)
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, and 41.
Methotrexate (MTX) 100 mg/m2 IV over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted) on days 1, 150 mg/m2 on day 11, 200 mg/m2 on day 21, 250 mg/m2 on day 31, and 300 mg/m2 on day 41.
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Total body irradiation (TBI) 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance.
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.
Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).
Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.
Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 84.
CNS prophylaxis
Methotrexate (MTX) IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation).
Age
Dose
1 - 1.99
8 mg
2 - 2.99
10 mg
3 - 8.99
12 mg
≥ 9
15 mg
12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.
Folinic acid (Leucovorin) 5 mg/m2 x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 10 - 11 and 31 - 32. (CNS3 also on days 17 - 18 and 24 - 25).
Ages 1 to 1.99: 8 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
Ages 2 to 2.99: 10 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
Ages 3 to 8.99: 12 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
Age 9 and older: 15 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
4-week course
Subsequent treatment
See protocol for details of treatment beyond induction
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Folinic acid (Leucovorin) 5 mg/m2 x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 3 - 4, 10 - 11, 17 - 18, and 24 - 25.
56-Day Course
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
Intermediate Dose Methotrexate (MTX) 2000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
MTX 200 mg/m2 IV infused over 30 minutes. This is followed, immediately, by MTX 1800 mg/m2 given by continuous IV infusion over 23.5 hours.
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX
Folinic acid (Leucovorin) 15 mg/m2 x a minimum of 5 doses PO or IV (given at 30, 36, 42, 48, and 54 hours after the START of ID MTX infusion) on days 2 - 3, 17 - 18, 31 - 32, and 45 - 46.
When IT therapy and HD MTX are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV MTX infusion. (hour -6 or +6, with 0 being the start of the MTX bolus).
63-Day Course
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
Total body irradiation (TBI) 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance.
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on day 1 ONLY.
Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).
Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5.
CNS prophylaxis
Methotrexate (MTX) IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation).
Age
Dose
1 - 1.99
8 mg
2 - 2.99
10 mg
3 - 8.99
12 mg
≥ 9
15 mg
12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
AIEOP-BFM ALL 2000: Möricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Aricò M, Bartram CR, Attarbaschi A, Silvestri D, Beier R, Basso G, Ratei R, Kulozik AE, Lo Nigro L, Kremens B, Greiner J, Parasole R, Harbott J, Caruso R, von Stackelberg A, Barisone E, Rössig C, Conter V, Schrappe M. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016 Apr 28;127(17):2101-12. Epub 2016 Feb 17. link to original articlecontains verified protocol in supplementPubMed NCT00430118; NCT00613457
Note: this regimen is of historic interest as an induction regimen; it is still occasionally used as pre-phase in patients too ill to get cytotoxic chemotherapy at time of diagnosis.
Chemotherapy
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
Sallan SE, Cammita BM, Cassady JR, Nathan DG, Frei E 3rd. Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results. Blood. 1978 Mar;51(3):425-33. link to original articlecontains verified protocolPubMed
Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.
Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
Age 9 and older: 15 mg IT once per day on days 8 & 29
4-week course
Subsequent treatment
See protocol for details of treatment beyond induction
References
COG AALL1131: Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. link to original articlelink to PMC articlePubMed NCT02883049
ALL-BFM 86: Reiter A, Schrappe M, Ludwig WD, Hiddemann W, Sauter S, Henze G, Zimmermann M, Lampert F, Havers W, Niethammer D, Odenwald E, Ritter J, Mann G, Welte K, Gadner H, Riehm H. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients: results and conclusions of the multicenter trial ALL-BFM 86. Blood. 1994 Nov 1;84(9):3122-33. link to original articlecontains verified protocolPubMed
DCLSG ALL-7: Kamps WA, Bökkerink JP, Hählen K, Hermans J, Riehm H, Gadner H, Schrappe M, Slater R, van den Berg-de Ruiter E, Smets LA, de Vaan GA, Weening RS, van Weerden JF, van Wering ER, den der Does-van den Berg A. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group protocol ALL-7 (1988-1991). Blood. 1999 Aug 15;94(4):1226-36. link to original articlePubMed
ALL-BFM 90: Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H; German-Austrian-Swiss ALL-BFM Study Group. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood. 2000 Jun 1;95(11):3310-22. link to original articlecontains verified protocolPubMed
Pooled subgroup analysis: Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. link to original articlePubMed
DCLSG ALL-8: Kamps WA, Bökkerink JP, Hakvoort-Cammel FG, Veerman AJ, Weening RS, van Wering ER, van Weerden JF, Hermans J, Slater R, van den Berg E, Kroes WG, van der Does-van den Berg A. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996). Leukemia. 2002 Jun;16(6):1099-111. link to original articlerefers to ALL-BFM 90 protocolPubMed
COG CCG-1961: Seibel NL, Steinherz PG, Sather HN, Nachman JB, Delaat C, Ettinger LJ, Freyer DR, Mattano LA Jr, Hastings CA, Rubin CM, Bertolone K, Franklin JL, Heerema NA, Mitchell TL, Pyesmany AF, La MK, Edens C, Gaynon PS. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 1;111(5):2548-55. link to original articlelink to PMC articlecontains verified protocolPubMed NCT00002812
ALL-BFM 95: Möricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dördelmann M, Löning L, Beier R, Ludwig WD, Ratei R, Harbott J, Boos J, Mann G, Niggli F, Feldges A, Henze G, Welte K, Beck JD, Klingebiel T, Niemeyer C, Zintl F, Bode U, Urban C, Wehinger H, Niethammer D, Riehm H, Schrappe M; German-Austrian-Swiss ALL-BFM Study Group. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008 May 1;111(9):4477-89. Epub 2008 Feb 19. Erratum in: Blood. 2009 Apr 30;113(18):4478. Dosage error in article text. link to original articlecontains verified protocolPubMed
Pooled subgroup analysis: Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. link to original articlePubMed
Intensification (randomized) or Cy/TBI with allo HSCT, depending on donor availability
References
UK MRC ALLX: Chessells JM, Bailey C, Wheeler K, Richards SM. Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia in first remission: experience in MRC UKALL X. Lancet. 1992 Sep 5;340(8819):565-8. link to original articlecontains verified protocolPubMed
Update: Chessells JM, Bailey C, Richards SM; Medical Research Council Working Party on Childhood Leukaemia. Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X. Lancet. 1995 Jan 21;345(8943):143-8. link to original articlePubMed
EORTC CLG 58951: De Moerloose B, Suciu S, Bertrand Y, Mazingue F, Robert A, Uyttebroeck A, Yakouben K, Ferster A, Margueritte G, Lutz P, Munzer M, Sirvent N, Norton L, Boutard P, Plantaz D, Millot F, Philippet P, Baila L, Benoit Y, Otten J; Children's Leukemia Group of the European Organisation for Research and Treatment of Cancer. Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951. Blood. 2010 Jul 8;116(1):36-44. Epub 2010 Apr 20. link to original articlelink to PMC articlecontains verified protocolPubMed NCT00003728
Update: Domenech C, Suciu S, De Moerloose B, Mazingue F, Plat G, Ferster A, Uyttebroeck A, Sirvent N, Lutz P, Yakouben K, Munzer M, Röhrlich P, Plantaz D, Millot F, Philippet P, Dastugue N, Girard S, Cavé H, Benoit Y, Bertrand Y; Children's Leukemia Group (CLG) of European Organisation for Research and Treatment of Cancer. Dexamethasone (6 mg/m2/day) and prednisolone (60 mg/m2/day) were equally effective as induction therapy for childhood acute lymphoblastic leukemia in the EORTC CLG 58951 randomized trial. Haematologica. 2014 Jul;99(7):1220-7. Epub 2014 Apr 11. link to original articlelink to PMC articlePubMed
Update: Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poirée M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cavé H, Rohrlich P, Bertrand Y, Benoit Y; Children–s Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer. Prolonged versus standard native E coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951. Haematologica. 2017 Oct;102(10):1727-1738. Epub 2017 Jul 27. link to original articlelink to PMC articlePubMed
Younger than 18: 2 mg/m2 (maximum dose of 2.5 mg) IV once per day on days 1, 8, 15, 22, 29
18 or older: 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29
Prednisolone (Millipred) 20 mg/m2 PO three times per day on days 1 to 29, then 10 mg/m2 PO three times per day on days 30 to 32, then 5 mg/m2 PO three times per day on days 33 to 35, then 2.5 mg/m2 PO three times per day on days 36 to 38
Note: the primary endpoint of CCG 1962 was incidence of high-titer ASNase antibodies in the first dose intensification, which is neither an efficacy nor a toxicity endpoint.
See protocol for details of treatment beyond induction
References
CCG 1962: Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, Ettinger AG, Ettinger LJ, Franklin J, Gaynon PS, Hilden JM, Lange B, Majlessipour F, Mathew P, Needle M, Neglia J, Reaman G, Holcenberg JS, Stork L. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood. 2002 Mar 15;99(6):1986-94. Erratum in: Blood 2002 Sep 1;100(5):1531. link to original articlePubMed
Methotrexate (MTX) 200 mg/m2 IV over 20 minutes, then 3800 mg/m2 IV continuous infusion over 23 hours and 40 minutes on days 1 & 8 (total dose: 8000 mg/m2)
Subsequent treatment
Reinduction
References
COG P9407: Dreyer ZE, Hilden JM, Jones TL, Devidas M, Winick NJ, Willman CL, Harvey RC, Chen IM, Behm FG, Pullen J, Wood BL, Carroll AJ, Heerema NA, Felix CA, Robinson B, Reaman GH, Salzer WL, Hunger SP, Carroll WL, Camitta BM. Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3). Pediatr Blood Cancer. 2015 Mar;62(3):419-26. Epub 2014 Nov 14. link to original articlelink to PMC articlePubMed NCT00002756
COG AALL0631: Brown PA, Kairalla JA, Hilden JM, Dreyer ZE, Carroll AJ, Heerema NA, Wang C, Devidas M, Gore L, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Borowitz MJ, Small D, Loh ML, Hunger SP. FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children's Oncology Group trial AALL0631. Leukemia. 2021 May;35(5):1279-1290. Epub 2021 Feb 23. Erratum in: Leukemia. 2021 Apr 12. link to original articlecontains verified protocol in supplementPubMed NCT00557193
POG 9005: Mahoney DH Jr, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP, Camitta B. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III trial. J Clin Oncol. 1998 Jan;16(1):246-54. link to original articlePubMed
POG 9006: Lauer SJ, Shuster JJ, Mahoney DH Jr, Winick N, Toledano S, Munoz L, Kiefer G, Pullen JD, Steuber CP, Camitta BM. A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial. Leukemia. 2001 Jul;15(7):1038-45. link to original articlePubMed
Consolidation after upfront therapy (including post-remission therapy)
Note that many of these regimens are complex and as such will be referred to by their study name, not by the individual drug names. This is also a phase of treatment often referred to as post-remission or postinduction therapy.
COG AALL0232: Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, Mattano LA Jr, Cole C, Eicher A, Haugan M, Sorenson M, Heerema NA, Carroll AA, Gastier-Foster JM, Borowitz MJ, Wood BL, Willman CL, Winick NJ, Hunger SP, Carroll WL. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232. J Clin Oncol. 2016 Jul 10;34(20):2380-8. Epub 2016 Apr 25. link to original articlelink to PMC articlecontains verified protocolPubMed NCT00075725
Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN, Wolff L, Uckun FM, Gaynon PS. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med. 1998 Jun 4;338(23):1663-71. link to original articlePubMed
Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. link to original articlecontains protocolPubMed
Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. link to original articlecontains verified protocolPubMed
ALL-SCT-BFM-2003: Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. link to original articlePubMed NCT01423747
COG AALL0232: Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, Mattano LA Jr, Cole C, Eicher A, Haugan M, Sorenson M, Heerema NA, Carroll AA, Gastier-Foster JM, Borowitz MJ, Wood BL, Willman CL, Winick NJ, Hunger SP, Carroll WL. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232. J Clin Oncol. 2016 Jul 10;34(20):2380-8. Epub 2016 Apr 25. link to original articlelink to PMC articlecontains verified protocolPubMed NCT00075725
Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
COG CCG-1991: Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. link to original articlelink to PMC articlePubMed NCT00005945
COG AALL0932: Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. link to original articlecontains verified protocolPubMed NCT01190930
Methotrexate (MTX) 200 mg/m2 IV once on day 1, then 250 mg/m2 IV once on day 11, then 300 mg/m2 IV once on day 21, then 350 mg/m2 IV once on day 31, then 400 mg/m2 IV once on day 41
Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
7-day cycle for 74 cycles or a total of 2 years from start of treatment
References
EORTC 58881: Millot F, Suciu S, Philippe N, Benoit Y, Mazingue F, Uyttebroeck A, Lutz P, Mechinaud F, Robert A, Boutard P, Marguerite G, Ferster A, Plouvier E, Rialland X, Behard C, Plantaz D, Dresse MF, Philippet P, Norton L, Thyss A, Dastugue N, Waterkeyn C, Vilmer E, Otten J; Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer. Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organisation for Research and Treatment of Cancer 58881 randomized phase III trial. J Clin Oncol. 2001 Apr 1;19(7):1935-42. link to original articlePubMed
Update: Duval M, Suciu S, Ferster A, Rialland X, Nelken B, Lutz P, Benoit Y, Robert A, Manel AM, Vilmer E, Otten J, Philippe N. Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial. Blood. 2002 Apr 15;99(8):2734-9. link to original articlePubMed
Update: van der Werff Ten Bosch J, Suciu S, Thyss A, Bertrand Y, Norton L, Mazingue F, Uyttebroeck A, Lutz P, Robert A, Boutard P, Ferster A, Plouvier E, Maes P, Munzer M, Plantaz D, Dresse MF, Philippet P, Sirvent N, Waterkeyn C, Vilmer E, Philippe N, Otten J. Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG. Leukemia. 2005 May;19(5):721-6. link to original articlePubMed
I-BFM-SG IR ALL: Conter V, Valsecchi MG, Silvestri D, Campbell M, Dibar E, Magyarosy E, Gadner H, Stary J, Benoit Y, Zimmermann M, Reiter A, Riehm H, Masera G, Schrappe M. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet. 2007 Jan 13;369(9556):123-31. link to original articlecontains verified protocolPubMed NCT00411541
Cycle 1: 5 mcg/day IV continuous infusion over 7 days, started on day 1, then 15 mcg/day IV continuous infusion over 21 days, started on day 8 (total dose: 350 mcg)
Cycles 2 to 5: 28 mcg/day IV continuous infusion over 28 days, started on day 1 (total dose per cycle: 784 mcg)
42-day cycle for up to 5 cycles
References
MT103-205: von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. link to original articlecontains verified protocolPubMed NCT01471782
Patients in this study were pediatric: ≤ 15 years old at diagnosis and ≤ 21 years old at time of treatment. No patients had CNS disease at time of treatment, and no patients received CNS prophylaxis.
Chemotherapy
Clofarabine (Clolar) 40 mg/m2 IV over 2 hours once per day on days 1 to 5, given first
Prophylactic steroids used for patients with greater than 30 x 109 blasts/L in the peripheral blood prior to treatment
5-day course
2 out of 25 patients received a second course of CCE as consolidation therapy. Responding patients were given allogeneic HSCT if a suitable donor was immediately available or were given consolidation courses of chemotherapy including multiple agents active against ALL cells, chosen according to the treating physician's preference."
References
Locatelli F, Testi AM, Bernardo ME, Rizzari C, Bertaina A, Merli P, Pession A, Giraldi E, Parasole R, Barberi W, Zecca M. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol. 2009 Nov;147(3):371-8. Epub 2009 Aug 29. link to original articlecontains verified protocolPubMed
2- to 6-week cycles, depending on response count recovery
References
Phase 1: Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R, Rytting M, Brandt M, Keating M, Plunkett W, Kantarjian H. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004 Feb 1;103(3):784-9. Epub 2003 Oct 9. link to original articlePubMed
Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V, Luchtman-Jones L, Rytting M, Bomgaars LR, Rheingold S, Ritchey K, Albano E, Arceci RJ, Goldman S, Griffin T, Altman A, Gordon B, Steinherz L, Weitman S, Steinherz P. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006 Apr 20;24(12):1917-23. link to original articlecontains protocolPubMed
See paper for details of treatment beyond induction
References
Rivera GK, Buchanan G, Boyett JM, Camitta B, Ochs J, Kalwinsky D, Amylon M, Vietti TJ, Crist WM; Pediatric Oncology Group. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse: a Pediatric Oncology Group study. N Engl J Med. 1986 Jul 31;315(5):273-8. link to original articlePubMed
See papers for details of treatment beyond induction block 1
References
POG 9310: Abshire TC, Pollock BH, Billett AL, Bradley P, Buchanan GR. Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood. 2000 Sep 1;96(5):1709-15. link to original articlePubMed
COG AALL01P2: Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, Camitta BM, Gaynon PS, Carroll WL. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected]. J Clin Oncol. 2008 Aug 20;26(24):3971-8. Erratum in: J Clin Oncol. 2008 Oct 1;26(28): 4697. link to original articlelink to PMC articlecontains verified protocolPubMed NCT00049569
COG AALL0433: Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2021 Jan 1;106(1):46-55. link to original articlelink to PMC articledoes not contain protocolPubMed NCT00381680
For patients achieving CR or CRi, day 1 dose was reduced to 0.5 mg/m2
21-day cycle for 1 cycle, then 28-day cycle for up to 5 cycles
References
MDACC 2009-0872: Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, York S, Ravandi F, Kwari M, Faderl S, Rios MB, Cortes J, Fayad L, Tarnai R, Wang SA, Champlin R, Advani A, O'Brien S. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012 Apr;13(4):403-11. Epub 2012 Feb 21. link to original articlecontains protocolPubMed NCT01134575
Age less than 2: 8 mg IT once per day on days 1 & 8
Age 2: 10 mg IT once per day on days 1 & 8
Age older than 2: 12 mg IT once per day on days 1 & 8
4-week course
Subsequent treatment
See paper for details of treatment beyond induction
References
CCLG ALL R3: Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. link to original articlecontains verified protocollink to PMC articlePubMed NCT00967057
Age less than 2: 8 mg IT once per day on days 1 & 8
Age 2: 10 mg IT once per day on days 1 & 8
Age older than 2: 12 mg IT once per day on days 1 & 8
4-week course
Subsequent treatment
See paper for details of treatment beyond induction
References
CCLG ALL R3: Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. link to original articlecontains verified protocollink to PMC articlePubMed NCT00967057
Up to 50 kg: 2 to 5 x 106 CTL019 transduced viable T-cells per kg body weight IV once on day 0
Greater than 50 kg: 1.0 to 2.5 x 108 CTL019 transduced viable T-cells IV once on day 0
One course
References
Pedi CART19: Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. Epub 2013 Mar 25. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. link to original articlelink to PMC articlePubMed NCT01626495
UPCC04409: Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. link to original articlelink to PMC articlePubMed NCT01029366
ELIANA: Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. link to original articlelink to supplementary protocolcontains verified protocol in supplementlink to PMC articlePubMed NCT02435849
COG AALL1331: Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. link to original articlePubMed NCT02101853
Amgen 20120215: Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Mergen N, Mohammad A, Kormany WN, Eckert C, Möricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. link to original articlecontains protocolPubMed NCT02393859
Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. link to original articlePubMed
Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. link to original articlePubMed
Further notes
Pediatric ALL regimens tend to be very complex. This list on ped-onc.org appears to be fairly comprehensive and includes regimen details for some of the common regimens e.g. COG-AALL0232. For now we will try to include a list of references here and potentially build these regimens here, over time.