T-cell acute lymphoblastic leukemia, pediatric

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This page contains studies that were specific to pediatric populations. For the more general T-cell acute lymphoblastic leukemia page, follow this link.
Last updated on 2024-12-02:17 regimens on this page
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=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia.
=Upfront therapy=
==COG AALL0434 protocol==
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Winter et al. 2015 (COG AALL0434)	2007-2014 	Phase 3 (E-RT-esc)	Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine	Seems to have longer DFS1 (primary endpoint)	Similar toxicity
1Reported efficacy is based on the 2020 update.
===Induction, Arms B (Nelarabine Arms)===
All Patients
====Chemotherapy====
*Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 4 (OR 5 OR 6)
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
*Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 30 mg/m2 PO twice per day on days 1 to 28 (Total of 60 mg/m2/day, DO NOT TAPER)
====CNS therapy, prophylaxis====
*Cytarabine (Ara-C) IT once at time of diagnostic lumbar puncture or Day 1
Age in years, rounded to the nearest hundredth	Initial Dose
1.00 to 1.99 	30 mg
2.00 to 2.99 	50 mg
3.00 or older 	70 mg
*Methotrexate (MTX) IT once per day on days 8, 29 (CNS3 patients on days 15, 22 ALSO)
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
29-day course
===Consolidation, Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine===
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
====Preceding treatment====
*Daunorubicin, Pegaspargase, Vincristine, Prednisone induction
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 minutes once per day on days 8, 50
**Must reduce urine specific gravity to less than or equal to 1.015 prior to administration
*Cytarabine (Ara-C) 75 mg/m2 IV over 1 to 30 minutes or SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
*Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
**DO NOT escalate or modify dose based on blood counts during this course. 
*Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 1 to 5, 43 to 47
*Pegaspargase (Oncaspar) 2500 units/m2 IM or IV over 1 to 2 hours once per day on days 22 & 64
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 22, 29, 64, 71
====CNS therapy, prophylaxis====
*Methotrexate (MTX) IT once per day on days 15, 22, 57, 64 (Omit Day 22 if CNS3 T-ALL)
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
*Whole-brain irradiation by the following risk-based criteria:
**CNS3 T-ALL: 1,800cGy in 10 once daily fractions.
**Intermediate/High Risk ARM B: 1,200 cGy in 8 once-daily fractions given during weeks 4 and 5 of consolidation
71-day course
====Subsequent treatment====
*Interim maintenance
===Interim Maintenance, with Capizzi MTX (Arms A and B)===
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
====Preceding treatment====
*Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine induction
====Chemotherapy====
*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
**If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose. 
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
*Pegaspargase (Oncaspar) 2500 units/m2 IM or IV over 1 to 2 hours once per day on days 2, 22
====CNS therapy, prophylaxis====
*Methotrexate (MTX) IT once per day on days 1 & 31
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Delayed Intensification, Nelarabine Arms (Arms B and D)===
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50 
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 minutes once on day 29
*Cytarabine (Ara-C) 75 mg/m2 SC or IV over 1 to 30 minutes once per day on days 29 to 32, 36 to 39
*Doxorubicin (Adriamycin) 25 mg/m2 IV push/infusion over 1 to 15 minutes once per day on days 1, 8, 15
*Pegaspargase (Oncaspar) 2500 units/m2 IM or IV over 1 to 2 hours once on day 4 (OR 5 OR 6), 43
*Thioguanine (Tabloid) 60 mg/m2 PO once per day on days 29 to 42
**Should not be given to patients receiving CRT (Arm D and CNS3 T-ALL patients)
*Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 29 to 33
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 7, 15 to 21 (10 mg/m2/day, divided twice per day). 
====CNS therapy, prophylaxis====
*Methotrexate (MTX) IT once per day on days 1, 29, 36
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
====Radiotherapy====
*Total body irradiation (TBI) by the following risk-based criteria:
**Arm D Only: 1,200 cGy in 8 once daily fractions to start on day 50 of DI
**CNS3 T-ALL: 1,800 cGy in 10 once daily fractions to start on day 50 of DI
63-day course
===Maintenance, Arms B and D===
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 57
*Mercaptopurine (6-MP) 75 mg/m2 PO once per day on days 1 to 28, 36 to 84
*Methotrexate (MTX) 20 mg/m2 PO once per day on days 8, 15, 22, 36, 43, 50, 57, 64, 71, 78
**No dose escalation recommended for the first maintenance cycle
**Thereafter, for ANC at least 1500 μL on 3 CBCs done over 6 weeks or 2 monthly CBCs, increase dose of methotrexate or mercaptopurine by 25%
*Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 29 to 33
**DO NOT Administer with other Chemotherapy agents
====Glucocorticoid therapy====
*Prednisone (Sterapred) 20 mg/m2 PO twice per day on days 1 to 5 and 57 to 61 (Total of 40 mg/m2/day, divided twice per day) 
====CNS prophylaxis====
*Methotrexate (MTX) IT once on day 1
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
 Repeat above cycle for a total of 3 cycles. 
3 cycles
===Maintenance, continuation after cycle 3 (Arms B and D)===
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, 57
*Mercaptopurine (6-MP) 75 mg/m2 PO once per day on days 1 to 84
*Methotrexate (MTX) 20 mg/m2 PO once per day on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
**No dose escalation recommended for the first maintenance cycle 
**Thereafter, for ANC at least 1500 μL on 3 CBCs done over 6 weeks or 2 monthly CBCs, increase dose of methotrexate or mercaptopurine by 25%
====Glucocorticoid therapy====
*Prednisone (Sterapred) 20 mg/m2 PO twice per day on days 1 to 5, 29 to 33, 57 to 61 (Total of 40 mg/m2/day, divided twice per day) 
====CNS prophylaxis====
*Methotrexate (MTX) IT once on day 1
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
====Duration====
*Girls T-ALL: Continue repeating 12 week cycles of maintenance therapy II until the total duration of therapy is two years from the start of Interim Maintenance (~ Week 121)
*Boys T-ALL: Continue to repeat 12 week cycles of Maintenance therapy II until the total duration of therapy is three years from the start of Interim Maintenance (~ Week 173). 
*T-NHL patients (regardless of gender): Continue to repeat 12 week cycles of maintenance therapy II until the total duration reaches two years from the start of Interim Maintenance (~ Week 121)
84-day course
===References===
# COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00408005
## Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article EuroPMC
## Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article EuroPMC
==COG AALL1231 Protocol Arm A==
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Teachey et al. 2022 (COG AALL1231)	2014-2017 	Phase 3 (C)	COG AALL1231 Protocol Arm B (with bortezomib)	Did not meet primary endpoint of EFS
Note: Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
===Induction===
 All T-ALL and T-LLy patients
====Chemotherapy====
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once on day 4, 18 
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
*Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 28 (DO NOT TAPER)
====CNS prophylaxis====
*Cytarabine (Ara-C) IT once on day 1 or at the time of diagnostic lumbar puncture (if within 72 hours of protocol initiation)
Age in years, rounded to the nearest hundredth	Initial Dose
1.00 to 1.99 	30 mg
2.00 to 2.99 	50 mg
3.00 or older 	70 mg
*Methotrexate (MTX) IT once per day on days 8 & 29
====CNS treatment====
**CNS3 patients also receive Methotrexate (MTX) IT once per day on days 15 & 22
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
===Consolidation===
 All T-ALL and T-LLy Patients
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day over 30 to 60 minutes on days 1, 29
*Cytarabine (Ara-C) 75 mg/m2 IV over 1 to 30 minutes or SC once per day on days 1 to 4, 8 to 11, 29 to 32, 36 to 39 
*Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 1 to 14, 29 to 42 
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 15, 43
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
====CNS prophylaxis====
*Methotrexate (MTX) IT once per day on days 1, 8, 15, 22
**CNS3 patients and CNS3 T-LLy: Omit days 15, 22
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Interim Maintenance, SR patients, with CMTX===
 SR Patients Receive After Consolidation
====Chemotherapy====
*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
**If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 2, 22
====CNS prophylaxis====
*Methotrexate (MTX) IT once per day on days 1 & 31
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Delayed Intensification===
 All T-ALL and T-LLy Patients
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 minutes once on day 29
*Cytarabine (Ara-C) 75 mg/m2 SC or IV over 1 to 30 minutes once per day on days 29 to 32, 36 to 39
*Doxorubicin (Adriamycin) 25 mg/m2 IV push or infusion over 1 to 15 minutes once per day on days 1, 8, 15
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 4, 18, 43
*Thioguanine (Tabloid) 60 mg/m2 PO once per day on days 29 to 42
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 7, 15 to 21 (10 mg/m2/day, divided twice per day)
====CNS prophylaxis====
*Methotrexate (MTX) IT once per day on days 1, 29, 36
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Delayed Intensification, IR patients===
 All T-ALL and T-LLy Patients
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 minutes once on day 29
*Cytarabine (Ara-C) 75 mg/m2 SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
*Doxorubicin (Adriamycin) 25 mg/m2 IV push or infusion over 1 to 15 minutes once per day on days 1, 8, 15
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours on day 4, 18, 43
*Thioguanine (Tabloid) 60 mg/m2 PO once per day on days 29 to 42
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 7, 15 to 21 (10 mg/m2/day, divided twice per day)
====CNS prophylaxis====
*Methotrexate (MTX) IT once per day on days 1, 29, 36
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Interim Maintenance, #1 with HDMTX - ALL IR Patients===
 SR and VHR T-ALL and T-LLy DO NOT RECEIVE
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
*Mercaptopurine (6-MP) 25 mg/m2 PO once per day on days 1 to 56
*High Dose Methotrexate (MTX) 5,000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 15, 29, 43. 
**Methotrexate (MTX) 500 mg/m2 IV infused over 30 minutes, then 4500 mg/m2 given by continuous IV infusion over 23.5 hours
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of high dose methotrexate infusion) on days 3, 4, 17, 18, 31, 32, 45, 46
====CNS prophylaxis====
*Methotrexate (MTX) IT once per day on days 1, 29, 36
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Interim Maintenance, #2 with CMTX - ALL IR Patients===
 IR T-ALL and T-LLy Patients receive this after DI as IM#2
====Chemotherapy====
*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
**If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 2, 22
====CNS prophylaxis====
*Methotrexate (MTX) IT once per day on days 1 & 31
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Intensification, Block 1 (VHR patients)===
 VHR Patients receive immediately after consolidation
====Chemotherapy====
*High Dose Methotrexate (MTX) 500 mg/m2 IV over 30 minutes once on day 1, then 4500 mg/m2 IV continuous infusion over 23.5 hours, started on day 1
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 6
*Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 1 to 6 hours every 12 hours x 5 doses on days 2 to 4
*High Dose Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours x 2 doses once on day 5 
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once on day 6
** Administer 3 hours after completion of the second high dose Cytarabine (Ara-C) infusion
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 10 mg/m2 IV or PO twice per day on days 1 to 5 (20 mg/m2/day, divided twice per day)
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of high dose methotrexate infusion) on days 3 & 4
*Filgrastim (Neupogen) 5 mcg/kg SC or IV once per day beginning on day 7 and until WBC count more than 3 x 109/L
**Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Maximum dose of 6 mg) SC once during the 7 to 11th day
====CNS prophylaxis, Triple Intrathecal Therapy====
*Methotrexate (MTX) by the following age-based criteria:
**1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
*Hydrocortisone (Cortef) by the following age-based criteria:
**1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
*Cytarabine (Ara-C) by the following age-based criteria:
**1 up to 2 years old: 16 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 20 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 24 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 30 mg IT on day 1, given 2 hours after the start of HD MTX infusion
===Intensification, Block 2===
====Chemotherapy====
*High Dose Methotrexate (MTX) 500 mg/m2 IV over 30 minutes once on day 1, then 4500 mg/m2 IV continuous infusion over 23.5 hours, started on day 1
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 6
*Ifosfamide (Ifex) 800 mg/m2 IV infusion over 1 hour every 12 hours x 5 doses on days 2 to 4 
**Start Immediately after completion of high dose Methotrexate (MTX) infusion. 
*Daunorubicin (Cerubidine) 30 mg/m2 IV over 1 to 15 minutes on day 5 
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours on day 6
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 10 mg/m2 IV or PO twice per day on days 1 to 5 (20 mg/m2/day, divided twice per day)
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of high dose methotrexate infusion) on days 3 & 4
*Mesna (Mesnex) 300 mg/m2 at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 2 to 4
*Filgrastim (Neupogen) 5 mcg/kg SC or IV once per day beginning on day 7 and until WBC count more than 3 x 109/L
**Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Max 6 mg/dose) SC once during the 7 to 11th day
====CNS prophylaxis, Triple Intrathecal Therapy====
*Methotrexate (MTX) by the following age-based criteria:
**1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
*Hydrocortisone (Cortef) by the following age-based criteria:
**1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
*Cytarabine (Ara-C) by the following age-based criteria:
**1 up to 2 years old: 16 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 20 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 24 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 30 mg IT on day 1, given 2 hours after the start of HD MTX infusion
===Intensification, Block 3===
====Chemotherapy====
*High Dose Cytarabine (Ara-C) 2,000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses total)
*Etoposide (Vepesid) 100 mg/m2 IV over 1 to 2 hours every 12 hours on days 3 to 5 (5 doses total)
**First dose to be given 12 hours after the start of the 4th high dose cytarabine on day 2
**Infusion rate should not exceed 300 mg/m2/hour (10 mg/kg/hour) 
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once on day 6 
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 10 mg/m2 IV or PO twice per day on days 1 to 5 (20 mg/m2/day, divided twice per day)
====Supportive therapy====
*Filgrastim (Neupogen) 5 mcg/kg SC or IV once per day beginning on day 7 and until WBC count more than 3 x 109/L
**Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Max 6 mg/dose) SC once during the 7 to 11th day
====CNS therapy, Triple Intrathecal Therapy====
*Methotrexate (MTX) by the following age-based criteria:
**1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
*Hydrocortisone (Cortef) by the following age-based criteria:
**1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
*Cytarabine (Ara-C) by the following age-based criteria:
**1 up to 2 years old: 16 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**2 up to 3 years old: 20 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**3 up to 9 years old: 24 mg IT on day 1, given 2 hours after the start of HD MTX infusion
**9 years old and older: 30 mg IT on day 1, given 2 hours after the start of HD MTX infusion
===Delayed Intensification===
 All T-ALL and T-LLy Patients
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 minutes once on day 29
*Cytarabine (Ara-C) 75 mg/m2 SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
*Doxorubicin (Adriamycin) 25 mg/m2 IV push or infusion over 1 to 15 minutes once per day on days 1, 8, 15
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 4, 18, 43 
*Thioguanine (Tabloid) 60 mg/m2 PO once per day on days 29 to 42
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 7, 15 to 21 (10 mg/m2/day, divided twice per day)
====CNS therapy, prophylaxis====
*Methotrexate (MTX) IT once per day on days 1, 29, 36
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Interim Maintenance, with CMTX===
 VHR Patients receive after DI
====Chemotherapy====
*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
**If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 2, 22
====CNS therapy, prophylaxis====
*Methotrexate (MTX) IT once per day on days 1 & 31
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
56-day course
===Maintenance, all patients===
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, 57 
*Mercaptopurine (6-MP) 75 mg/m2 PO once per day on days 1 to 84
*Methotrexate (MTX) 20 mg/m2 PO once per day on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
**Omit day 29 of the first FOUR cycles for SR T-ALL and T-LLy patients
**Omit day 29 of the first TWO cycles for IR T-ALL and T-LLy patients
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 5, 29 to 33, 57 to 61 (6 mg/m2/day, divided twice per day) 
====CNS therapy, prophylaxis====
*Methotrexate (MTX) IT once on day 1
**Also on day 29 of the first FOUR cycles for SR patients
**Also on day 29 of the first TWO cycles for IR patients
Age in years, rounded to the nearest hundredth	Dose
1.00 to 1.99 	8 mg
2.00 to 2.99 	10 mg
3.00 to 8.99 	12 mg
9.00 or older 	15 mg
====Radiotherapy====
*Total body irradiation (TBI) during the first cycle of maintenance, by the following histology- and risk-based criteria:
**T-ALL AND CNS1 VHR: 1200 cGy
**T-ALL AND CNS2 VHR: 1200 cGy
**T-ALL AND CNS3 IR: 1800 cGy
**T-ALL AND CNS3 VHR: 1800 cGy
**T-LLy AND CNS3 IR: 1800 cGy
**T-LLy AND CNS3 VHR: 1800 cGy
Duration of therapy:
*SR and IR T-ALL Girls: repeat 12 week cycles of maintenance for a total duration of 2 years from Interim Maintenance start.
*VHR T-ALL Girls: Repeat 12 week cycles of maintenance for a total duration of 2 years from Intensification Block 1 start. 
*SR and IR T-ALL Boys: repeat 12 week cycles of maintenance for a total duration of 3 years from Interim Maintenance start.
*VHR T-ALL Boys: Repeat 12 week cycles of maintenance for a total duration of 3 years from Intensification Block 1 start. 
*T-LLy regardless of gender: repeat 12 week cycles of maintenance for a total duration of 2 years from Interim Maintenance start.
===References===
# COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00408005
## Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article EuroPMC
## Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article EuroPMC
# COG AALL1231: Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. Epub 2022 Mar 10. link to original article link to PMC article EuroPMC NCT02112916
=Pre-phase=
==Methylprednisolone monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Place et al. 2015 (DFCI 05-001)	2005-2011 	Non-randomized part of phase 3 RCT
Burns et al. 2020 (DFCI 11-001)	2012-2015 	Non-randomized part of phase 3 RCT
Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001. 
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) 8 mg/m2 IV three times per day on days 1 to 3
3-day course
====Subsequent treatment====
*DFCI 05-001: Doxorubicin, L-asparaginase, Methotrexate, Vincristine, Methylprednisolone versus Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone induction
*DFCI 11-001: Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone versus Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone induction
===References===
# DFCI 05-001: Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. Epub 2015 Nov 6. link to original article EuroPMC NCT00400946
## Pooled update: Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC
# DFCI 11-001: Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01574274
## Update: Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. Epub 2021 Jul 6. link to original article EuroPMC
=Upfront induction therapy=
==Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone==
===Regimen, modified ABFM===
Study 	Dates of enrollment 	Evidence
Sato et al. 2023 (ALL-T11)	2011-12-01 to 2017-11-30	Phase 2
Note: Day counts included a 7-day pre-phase, not shown here.
====Chemotherapy====
*Daunorubicin (Cerubidine) 30 mg/m2 IV once per day on days 8, 15, 22, 29
*Asparaginase (Elspar) 5000 units/m2 IM or IV once per day on days 12, 15, 18, 21, 24, 27, 30, 33
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29
====Glucocorticoid therapy====
*Dexamethasone (Decadron) by the following age-based criteria:
**Younger than 10 years old: 10 mg/m2/day PO on days 8 to 28
**10 years old or older: 10 mg/m2/day PO on days 8 to 14, 22 to 28
====CNS therapy, prophylaxis====
*Cytarabine (Ara-C) by the following age-based criteria:
**Younger than 1 year old: 16 mg IT once per day on days 12 & 33
**1 to 1.99 years old: 20 mg IT once per day on days 12 & 33
**2 to 2.99 years old: 26 mg IT once per day on days 12 & 33
**3 years old or older: 30 mg IT once per day on days 12 & 33
*Methotrexate (MTX) by the following age-based criteria:
**Younger than 1 year old: 6 mg IT once per day on days 12 & 33
**1 to 1.99 years old: 8 mg IT once per day on days 12 & 33
**2 to 2.99 years old: 10 mg IT once per day on days 12 & 33
**3 years old or older: 12 mg IT once per day on days 12 & 33
*[[Prednisolone (Millipred) by the following age-based criteria
**Younger than 1 year old: 4 mg IT once per day on days 12 & 33
**1 to 1.99 years old: 6 mg IT once per day on days 12 & 33
**2 to 2.99 years old: 8 mg IT once per day on days 12 & 33
**3 years old or older: 10 mg IT once per day on days 12 & 33
4-week course
====Subsequent treatment====
*See paper for details
===References===
#ALL-T11: Sato A, Hatta Y, Imai C, Oshima K, Okamoto Y, Deguchi T, Hashii Y, Fukushima T, Hori T, Kiyokawa N, Kato M, Saito S, Anami K, Sakamoto T, Kosaka Y, Suenobu S, Imamura T, Kada A, Saito AM, Manabe A, Kiyoi H, Matsumura I, Koh K, Watanabe A, Miyazaki Y, Horibe K. Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group. Lancet Haematol. 2023 Jun;10(6):e419-e432. Epub 2023 May 8. Erratum in: Lancet Haematol. 2023 Jun;10(6):e399. link to original article dosing details in supplement have been reviewed by our editors EuroPMC jRCTs041180145
==Daunorubicin, Pegaspargase, Vincristine, Dexamethasone==
===Regimen, modified ABFM===
Study 	Dates of enrollment	Evidence
Vora et al. 2013 (UKALL 2003)	2003-2011 	Non-randomized part of phase 2 RCT
====Chemotherapy====
*Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 4 & 18
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 28
====CNS therapy, prophylaxis====
*Cytarabine (Ara-C) by the following age-based criteria:
**1 to 1.99 years old: 30 mg IT once on day 1
**2 to 2.99 years old: 50 mg IT once on day 1
**3 years old or older: 70 mg IT once on day 1
*Methotrexate (MTX) by the following age-based criteria:
**1 to 1.99 years old: 8 mg IT once per day on days 8 & 29
**2 to 2.99 years old: 10 mg IT once per day on days 8 & 29
**3 to 8.99 years old: 12 mg IT once per day on days 8 & 29
**9 years old or older: 15 mg IT once per day on days 8 & 29
4-week course
====Subsequent treatment====
*Cyclophosphamide, cytarabine, mercaptopurine, pegaspargase, vincristine consolidation
===References===
# UKALL 2003: Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. Epub 2013 Feb 7. link to original article EuroPMC ISRCTN07355119
==Daunorubicin, Pegaspargase, Vincristine, Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Winter et al. 2015 (COG AALL0434)	2007-2014 	Non-randomized part of phase 3 RCT
====Chemotherapy====
*Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
*Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 5 +/- 1 day
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 30 mg/m2 PO twice per day on days 1 to 28
4-week course
====Subsequent treatment====
*Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine
===References===
# COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00408005
## Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article EuroPMC
## Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article EuroPMC
==DOLP==
DOLP: Daunorubicin, Oncovin (Vincristine), L-Asparaginase, Prednisone
DVPA: Daunorubicin, Vincristine, Prednisone, Asparaginase
===Regimen, BFM 76/79 Phase I===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gaynon et al. 1988 (CCG-106) 	1983-05 to 1984-11 	Phase 3 (E-esc)	1. Control regimen 	Seems to have higher EFS36
Gaynon et al. 1988 (CCG-106) 	1983-05 to 1984-11 	Phase 3 (E-esc)	2. New York regimen 	Did not meet primary endpoint of EFS36
Steinherz et al. 1998 (CCG-123)	1983-1985 	Phase 3 (C) 	1. LSA2-L2 & WBRT2. LSA-L23. New York regimen	Did not meet primary endpoint of EFS
Note: the specific days of L-asparaginase are not specified; the schedule here is similar to those of other similar protocols.
====Chemotherapy====
*Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
*Asparaginase (Elspar) 6000 units/m2 IM once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 28, then tapered over 2 weeks
====CNS therapy====
*Methotrexate (MTX) IT once per day on days 1, 15, 29 (dose not specified)
6-week course
====Subsequent treatment====
*BFM 76/79 Phase II
===References===
# CCG-106: Gaynon PS, Steinherz PG, Bleyer WA, Ablin AR, Albo VC, Finklestein JZ, Grossman NJ, Littman PS, Novak LT, Pyesmany AF, Sather HN, Hammond GD. Intensive therapy for children with acute lymphoblastic leukaemia and unfavourable presenting features: early conclusions of study CCG-106 by the Childrens Cancer Study Group. Lancet. 1988 Oct 22;2(8617):921-4. link to original article EuroPMC
# CCG-123: Steinherz PG, Gaynon PS, Breneman JC, Cherlow JM, Grossman NJ, Kersey JH, Johnstone HS, Sather HN, Trigg ME, Uckun FM, Bleyer WA. Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group. Cancer. 1998 Feb 1;82(3):600-12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Place et al. 2015 (DFCI 05-001)	2005-2011 	Phase 3 (E-switch-ic)	Doxorubicin, L-asparaginase, Methotrexate, Vincristine, Methylprednisolone	Did not meet secondary endpoint of DFS	Less anxiety
Burns et al. 2020 (DFCI 11-001)	2012-2015 	Phase 3 (C) 	Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone 	Not reported 	
Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001. Day numbering takes into account the pre-phase.
====Preceding treatment====
*Methylprednisolone pre-phase
====Chemotherapy====
*Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 4 & 5
*Methotrexate (MTX) 40 mg/m2 IV once on day 6
*Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 7
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 4, 11, 18, 25
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) 8 mg/m2 IV three times per day on days 4 to 32
====Supportive therapy====
*Dexrazoxane (Zinecard) 300 mg/m2 IV once per day on days 4 & 5
28-day course
====CNS therapy, prophylaxis====
*Cytarabine (Ara-C) IT once per day on days 1 & 18
**Day 18 dose is admixed with MTX and HC
*Methotrexate (MTX) IT once per day on days 18 & 32
**Day 18 dose is admixed with Ara-C and HC
*Hydrocortisone (Cortef) IT once on day 18, admixed with Ara-C and MTX
====Subsequent treatment====
*Doxorubicin, Mercaptopurine, Methotrexate, Vincristine consolidation (IA)
===References===
# DFCI 05-001: Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. Epub 2015 Nov 6. link to original article EuroPMC NCT00400946
## Pooled update: Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC
# DFCI 11-001: Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01574274
## Update: Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. Epub 2021 Jul 6. link to original article EuroPMC
=Consolidation after upfront therapy=
==Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Winter et al. 2015 (COG AALL0434)	2007-2014 	Phase 3 (E-RT-esc)	Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine	Seems to have longer DFS1 (primary endpoint)	Similar toxicity
1Reported efficacy is based on the 2020 update.
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
====Preceding treatment====
*Daunorubicin, Pegaspargase, Vincristine, Prednisone induction
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 8 & 50
*Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
*Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
*Nelarabine (Arranon) 650 mg/m2 IV once per day on days 1 to 5, 43 to 47
*Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 22 & 64
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 22, 64, 71
====CNS therapy, prophylaxis====
*Methotrexate (MTX) (dose not specified) IT on days 15, 22, 57, 64
*Whole-brain irradiation in some arms (see paper for details)
71-day course
====Subsequent treatment====
*Interim maintenance; see paper for details
===References===
# COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00408005
## Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article EuroPMC
## Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article EuroPMC
==Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine==
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy	Comparative Toxicity
Winter et al. 2015 (COG AALL0434)	2007-2014 	Phase 3 (C)	Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine	Not reported 	Similar toxicity
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
====Preceding treatment====
*Daunorubicin, Pegaspargase, Vincristine, Prednisone induction
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 8 & 50
*Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
*Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
*Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 22 & 64
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 22, 64, 71
====CNS therapy, prophylaxis====
*Methotrexate (MTX) (dose not specified) IT on days 15, 22, 57, 64
*Whole-brain irradiation in some arms (see paper for details)
71-day course
====Subsequent treatment====
*Interim maintenance; see paper for details
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Teachey et al. 2022 (COG AALL1231)	2014-2017 	Non-randomized part of phase 3 RCT
Note: Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
====Preceding treatment====
*Daunorubicin, pegaspargase, vincristine, dexamethasone induction
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 29
*Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
*Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 1 to 14, 29 to 42
**Dose may be modified based on TPMT status
*Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 15 & 43
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
====Supportive therapy====
*Mesna (Mesnex) "is not required for this dose of cyclophosphamide, but may be administered at institutional discretion."
====CNS therapy, prophylaxis====
*Methotrexate (MTX) by the following age-based criteria, for CNS3:
**1 to 1.99 years old: 8 mg IT once per day on days 1 & 8
**2 to 2.99 years old: 10 mg IT once per day on days 1 & 8
**3 to 8.99 years old: 12 mg IT once per day on days 1 & 8
**9 years old or older: 15 mg IT once per day on days 1 & 8
50-day course
====Subsequent treatment====
*See protocol for details of treatment beyond consolidation, which is guided by MRD status obtained at the end of induction.
===References===
# COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00408005
## Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article EuroPMC
## Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article EuroPMC
# COG AALL1231: Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. Epub 2022 Mar 10. link to original article link to PMC article EuroPMC NCT02112916
==Doxorubicin, Mercaptopurine, Methotrexate, Vincristine, Prednisone==
===Regimen variant #1, high-dose MTX===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Asselin et al. 2011 (POG 9404)	1996-2001 	Phase 3 (E-esc)	Doxorubicin, Mercaptopurine, Methotrexate, Vincristine, Prednisone; low-dose MTX	Seems to have longer EFS (primary endpoint)
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Chemotherapy====
*Doxorubicin (Adriamycin) 30 mg/m2 (maximum dose of 60 mg) IV once per day on days 1, 2, 22
*Mercaptopurine (6-MP) 50 mg/m2 (maximum dose of 100 mg) PO once per day on days 22 to 36
*Methotrexate (MTX) 40 mg/m2 (maximum dose of 80 mg) (route not specified) once on day 2, given 8 to 24 hours after doxorubicin, then 500 mg/m2 (maximum dose of 1000 mg) IV over 30 minutes once on day 22, then 4500 mg/m2 (maximum dose of 9000 mg) IV continuous infusion over 23.5 hours
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2/day (maximum dose of 80 mg/day) (route not specified) on days 1 to 22
====Supportive therapy====
*Dexrazoxane (Zinecard) 300 mg/m2 (maximum dose of 600 mg) IV once per day on days 1, 2, 22, given immediately before each dose of doxorubicin
42-day course
===Regimen variant #2, low-dose MTX===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Asselin et al. 2011 (POG 9404)	1996-2001 	Phase 3 (C)	Doxorubicin, Mercaptopurine, Methotrexate, Vincristine, Prednisone; high-dose MTX	Seems to have shorter EFS
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Chemotherapy====
*Doxorubicin (Adriamycin) 30 mg/m2 (maximum dose of 60 mg) IV once per day on days 1, 2, 22
*Mercaptopurine (6-MP) 50 mg/m2 (maximum dose of 100 mg) PO once per day on days 22 to 36
*Methotrexate (MTX) 40 mg/m2 (maximum dose of 80 mg) (route not specified) once on day 2, given 8 to 24 hours after doxorubicin
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2/day (maximum dose of 80 mg/day) (route not specified) on days 1 to 22
====Supportive therapy====
*Dexrazoxane (Zinecard) 300 mg/m2 (maximum dose of 600 mg) IV once per day on days 1, 2, 22, given immediately before each dose of doxorubicin
42-day course
===References===
# POG 9404: Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchison R, Lipshultz SE, Camitta BM. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood. 2011 Jul 28;118(4):874-83. Epub 2011 Apr 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==Etoposide & TBI, then allo HSCT==
===Regimen===
Study 	Dates of enrollment	Evidence
Peters et al. 2015 (ALL-SCT-BFM 2003)	2003-2011 	Non-randomized
===References===
# 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 article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 article EuroPMC
# 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 article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 article EuroPMC
# 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 article EuroPMC NCT01423747
==L-asparaginase monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Amylon et al. 1999 (POG 8704)	1987-1992 	Phase 3 (E-esc)	No L-asp 	Higher CRR
====Chemotherapy====
*Asparaginase (Elspar) 25,000 units/m2 IM once on day 1
7-day cycle for 20 cycles
===References===
# POG 8704: Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M, Katz J, Yu A, Laver J, Ravindranath Y, Kurtzberg J, Desai S, Camitta B, Murphy SB. Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study. Leukemia. 1999 Mar;13(3):335-42. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
=Interim maintenance=
==Mercaptopurine, Methotrexate, Pegaspargase, Vincristine==
===Regimen variant #1, Capizzi MTX===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Winter et al. 2015 (COG AALL0434)	2007-2014 	Phase 3 (C)	Interim maintenance; BFM HDMTX	Seems to have longer OS1
1Reported efficacy is based on the 2018 update.
====Preceding treatment====
*Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine induction
====Chemotherapy====
*Mercaptopurine (6-MP) 25 mg/m2 PO once per day on days 1 to 56
*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
*Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 2 & 22
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 15, 29, 43
====CNS prophylaxis====
*Methotrexate (MTX) (dose not specified) IT once per day on days 1 & 29
8-week course
====Subsequent treatment====
*Delayed intensification
===Regimen variant #2, HD-MTX===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Winter et al. 2015 (COG AALL0434)	2007-2014 	Phase 3 (C)	Interim maintenance; COG C-MTX	Seems to have shorter OS1
1Reported efficacy is based on the 2018 update.
====Preceding treatment====
*Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine induction
====Chemotherapy====
*Mercaptopurine (6-MP) 25 mg/m2 PO once per day on days 1 to 56
*Methotrexate (MTX) 5000 mg/m2 IV once per day on days 1, 15, 29, 43
*Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 2 & 22
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 15, 29, 43
====CNS prophylaxis====
*Methotrexate (MTX) (dose not specified) IT once per day on days 1 & 29
8-week course
====Subsequent treatment====
*Delayed intensification
===References===
# COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00408005
## Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article EuroPMC
## Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article EuroPMC
=Relapsed or refractory=
==Mitoxantrone, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Parker et al. 2010 (CCLG ALL R3)	2003-2007 	Phase 3, fewer than 20 pts in this subgroup (E-switch-ic)	Idarubicin, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone	Did not meet primary endpoint of PFS
Note: per the protocol, this regimen is intended only for patients 18 and younger and for patients allergic to pegaspargase. This is the same regimen used in relapsed B-ALL, but this subgroup did not have a statistically significant difference between the regimens.
====Chemotherapy====
*Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 & 8
*Asparaginase Erwinia chrysanthemi (Erwinaze) 20,000 units IM once per day on days 3, 5, 7, 9, 11, 13, 18, 20, 22, 24, 26, 28
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 3, 10, 17, 24
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg/m2 PO once per day on days 1 to 5, 15 to 19
====CNS therapy, prophylaxis====
*Methotrexate (MTX) by the following age-based criteria:
**Younger than 2 years old: 8 mg IT once per day on days 1 & 8
**Age 2: 10 mg IT once per day on days 1 & 8
**Older than 2 years old: 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 article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00967057
==Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Parker et al. 2010 (CCLG ALL R3)	2003-2007 	Phase 3, fewer than 20 pts in this subgroup (E-switch-ic)	Idarubicin, Pegaspargase, Vincristine, Dexamethasone	Did not meet primary endpoint of PFS
Note: per the protocol, this regimen is intended only for patients 18 and younger. This is the same regimen used in relapsed B-ALL, but this subgroup did not have a statistically significant difference between the regimens.
====Chemotherapy====
*Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 & 8
*Pegaspargase (Oncaspar) 1000 units/m2 IM once per day on days 3 & 18
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 3, 10, 17, 24
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg/m2 PO once per day on days 1 to 5, 15 to 19
====CNS therapy, prophylaxis====
*Methotrexate (MTX) by the following age-based criteria:
**Younger than 2 years old: 8 mg IT once per day on days 1 & 8
**Age 2: 10 mg IT once per day on days 1 & 8
**Older than 2 years old: 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 article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00967057
==Nelarabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Berg et al. 2005 	1997-2002 	Phase 2 (RT)	ORR: 14-55%
Zwaan et al. 2017 (GSK 111081)	2009-2014 	Phase 4 	ORR: 39%
====Chemotherapy====
*Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 1 to 5
21-day cycles
===References===
# Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, Billett A, Kurtzberg J, Reaman G, Gaynon P, Whitlock J, Krailo M, Harris MB; Children's Oncology Group. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005 May 20;23(15):3376-82. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# GSK 111081: Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, Ranganathan S, Leverger G. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017 Oct;179(2):284-293. Epub 2017 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00866671
Category:T-cell acute lymphoblastic leukemia regimens
Category:Disease-specific pages
Category:Acute lymphoblastic leukemias
Category:T-cell leukemias
Category:Pediatric hematologic neoplasms