Table 2.

Augmented and standard BFM chemotherapy regimens.

Induction phase (5 weeks):       • VCR† 1.5 mg/m2/day IV D0,7,14,21       • PDN 60 mg/m2/day PO D0–27       • ASP 6000 units/m2/day IM thrice weekly for 9 doses starting week 1       • Daunomycin 25 mg/m2/day IV D0,7,14,21       • ARA-C 70 mg IT D0       • MTX 12 mg IT D14
Stratify into risk groups
Standard BFM	Augmented BFM
Consolidation (5 weeks): CTX 1000 mg/m2/day IV D0,14 6-MP 60 mg/m2/day PO D0–27 ARA-C 75 mg/m2/day SQ/IV D1–4,8–11,15–18, 22–25 MTX 12 mg IT D1,8,15,22 Radiotherapy‡	Consolidation (9 weeks): CTX 1000 mg/m2/day IV D0,28 6-MP 60 mg/m2/day PO D0–13,28–41 ARA-C 75 mg/m2/day SQ/IV D1–4,8–11,29–32,36–39 VCR† 1.5 mg/m2/day IV D14,21,42,49 ASP 6000 units/m2/day IM D14,16,18,21, 23,25,42,44,46,49,51,53 MTX 12 mg IT D1,8,15,22 Radiotherapy‡
Interim maintenance (8 weeks): 6-MP 60 mg/m2/day PO D0–41 MTX 15 mg/m2/day PO D0,7,14,21,28,35	Interim maintenance 1 (8 weeks): VCR† 1.5 mg/m2/day IV D0,10,20,30,40 MTX 100 mg/m2/day IV D0,10,20,30,40 (escalate by 50 mg/m2/dose until toxicity) ASP 15,000 units/m2/day IM D1,11,21,31,41
Delayed intensification – Part 1 (Reinduction, 4 weeks): VCR† 1.5 mg/m2/day IV D0,14,21 DEX 10 mg/m2/day PO D0–20 DXR 25 mg/m2/day IV D0,7,14 ASP 6000 U/m2/day IM D3,5,7,10,12,14	Delayed intensification – Part 1 (Reinduction, 4 weeks): VCR† 1.5 mg/m2/day IV D0,14,21 DEX 10 mg/m2/day PO D0–20 DXR 25 mg/m2/day IV D0,7,14 ASP 6000 U/m2/day IM D3,5,7,10,12,14
Delayed intensification – Part 2 (Reconsolidation, 3 weeks): CTX 1000 mg/m2/day IV D28 6-TG 60 mg/m2/day PO D28–41 ARA-C 75 mg/m2/day SQ/IV D29–32,36–39 VCR† 1.5 mg/m2/day IV D42,49 MTX 12 mg IT D29,36	Delayed intensification – Part 2 (Reconsolidation, 4 weeks): CTX 1000 mg/m2/day IV D28 6-TG 60 mg/m2/day PO D28–41 ARA-C 75 mg/m2/day SQ/IV D29–32,36–39 VCR† 1.5 mg/m2/day IV D42,49 ASP 6000 U/m2/day IM D42,44,46,49,51,53 MTX 12 mg IT D29,36
Maintenance (12 weeks): VCR† 1.5 mg/m2/day IV D0,28,56 PDN 40 mg/m2/day PO D0–4,28–32,56–60 MTX 20 mg/m2/day PO D7,14,21,28,35,42,49, 56,63,70,77 6-MP 75 mg/m2/day PO D0–83 MTX 12 mg IT D0	Interim maintenance 2 (8 weeks): Same as interim maintenance 1 with addition of: MTX 12 mg IT D0,20,40
	Delayed intensification – Part 2 (same as for delayed intensification part 1)
	Maintenance (12 weeks): Same regimen as maintenance in standard BFM except prednisone dose is 60 mg/m2/day PO D0–4,28–32,56–60
Maintenance repeated for 6–8 cycles

^†Vincristine dose maximized at 2 mg.

^‡Radiotherapy for CNS prophylaxis (1800 cGy in 10 fractions) delivered during the first 2 weeks of consolidation therapy. Patients with CNS involvement at diagnosis received 2400 cGy to the cranial midplane in 12 fractions and 600 cGy to the spinal cord in 3 fractions.

Abbreviations: ARA-C = cytarabine, ASP = L-asparaginase, CTX = cyclophosphamide, DEX = dexamethasone, DXR = doxorubicin, 6-MP = 6-mercaptopurine, MTX = methotrexate, PDN = prednisone, 6-TP = 6-thioguanine, VCR = vincristine. IT = intrathecal, IM = intramuscular, IV = intravenous, PO=orally, SQ=subcutaneous.