Table 1. Chemotherapy Regimens.

Induction
Prednisone	40 mg/m2 PO in 3 divided doses for 28 d
Vincristine	1.5 mg/m2 IV days 1, 8, 15, and 22 (maximum dose 2 mg)
Doxorubicin	30 mg/m2 IV on days 1, 2
Asparaginase (randomized)
PEG	2500 U/m2 IM days 1, 8, 15, and 22 or
Escherichia coli	10,000 U/m2 IM days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26
Intrathecal therapy (age adjusted): days 1, 8, and 22 (also days 15 and 29 if CNS disease)
Age (y)	< 1	1	2	3-8	≥ 9
MTX	7.5	8	10	12	15
HDC	7.5	8	10	12	15
Ara-C	15	16	20	24	30
Consolidation 1
Ifosfamide	2.8 g/m2 IV days 1-5 with MESNA 350 mg/m2 IV q 3h × 8, days 1-5
Etoposide	100 mg/m2 IV days 1-5
G-CSF	5 μg/kg SC daily until ANC ≥ 5000 or > 1500 on 2 occasions (after the ANC nadir)
Consolidation 2
Ara-C	1 g/m2 IV over 6 h days 1-4
Idarubicin	5 mg/m2 IV days 1-4
G-CSF	as per consolidation 1
If cumulative lifetime dose of anthracycline (doxorubicin equivalents) is 450 mg/m2, substitute PEG asparaginase (2500 U/m2) weekly × 2 for idarubicin
Patients with a closely matched (6/6 or 5/6) related donor may be removed from study for a stem cell transplant after Consolidation 2
Continuation (5 cycles)
Week 1
Ifosfamide	3.4 g/m2 IV days 1-3 with MESNA 425 mg/m2 IV q 3h × 8, days 1-3
Etoposide	100 mg/m2 IV days 1-3
Week 4
6-thioguanine	75 mg/m2 PO days 1-14
Methotrexate	25 mg/m2 PO q 6 h × 4, days 1 and 8
Leucovorin	5 mg/m2 PO/IV q 12 h × 3 doses at days 3 and 10
Triple IT	day 1; doses as per induction
Week 6
Ara-C	1 gm/m2 IV over 6 h days 1-3
Idarubicin	5 mg/m2 IV days 1-3; discontinue if cumulative lifetime dose (doxorubicin equivalents) approaches 450 mg/m2
Week 9
Dexamethasone	8 mg/m2 PO in 3 divided doses days 1-14
Vincristine	2 mg/m2 IV days 1 and 8 (maximum dose 2 mg)
PEG Asparaginase	2500 U/m2 IM days 1 and 8

Patients with combined CNS and systemic relapse will have cranial (1800 cGy) and spinal (1200 cGy) radiation delayed until 2 cycles of continuation therapy have been delivered (approximately 6 mo into therapy).