Combination Chemotherapy Plus Steroid Therapy in Treating Children With Acute Lymphoblastic Leukemia or Lymphoblastic Non-Hodgkin's Lymphoma

OBJECTIVES: * Compare the value of dexamethasone (DM) vs prednisolone (PRDL) administered during induction therapy, in terms of event-free and overall survival, in children with acute lymphoblastic leukemia (ALL) or lymphoblastic non-Hodgkin's lymphoma (LNHL). * Assess the value of increasing the number of administrations of asparaginase during consolidation and late intensification therapy, in terms of disease-free and overall survival, in children without very high-risk (VHR) features. * Compare the response rate in children treated with prephase therapy comprising DM vs PRDL and intrathecal methotrexate. * Compare the incidence and grade of toxic effects of these treatment regimens in these children. * Compare the long-term effects of these treatment regimens on growth and pubertal development, neurocognitive, cardiac, and endocrine function, and incidence of aseptic bone necrosis in these children. * Evaluate the proportion of children with VHR disease when defined according to extended VHR criteria, and assess the prognostic importance of the new VHR features (cytogenetics and minimal-residual disease). * Compare the feasibility of the VHR chemotherapy protocol in patients treated with DM vs PRDL. OUTLINE: This is a randomized, multicenter study. Patients are stratified for prephase therapy according to center, disease (acute lymphoblastic leukemia \[ALL\] vs non-Hodgkin's lymphoma \[NHL\]), WBC for ALL patients (less than 10,000/mm\^3 vs 10,000/mm\^3 to less than 100,000/mm\^3 vs greater than 100,000/mm\^3), stage for NHL patients (I or II vs III or IV), and whether prephase already started (yes vs no). Patients are stratified for protocol II therapy according to center, risk group (very low risk \[VLR\] vs average risk 1 \[AR1\] vs average risk 2 \[AR2\]), and treatment arm at first randomization. * Prephase: Patients are randomized to 1 of 2 treatment arms * Arm I: Patients receive oral prednisolone (PRDL) twice daily or methylprednisolone IV over 1 hour every 12 hours on days 1-7. * Arm II: Patients receive dexamethasone (DM) orally twice daily or IV over 1 hour every 12 hours on days 1-7. Patients in both arms also receive methotrexate (MTX) intrathecally (IT) on day 1. * Protocol IA (days 8-35): * VLR patients: Patients receive either oral PRDL or oral DM (depending on earlier randomization) on days 8-28; vincristine (VCR) IV on days 8, 15, 22, and 29; daunorubicin (DNR) IV over 1-4 hours on days 8 and 15; MTX IT on days 12 and 25; and asparaginase (ASP) IV over 1 hour or intramuscularly (IM) on days 12, 15, 18, 22, 25, 29, 32, and 35. * AR1 patients: Patients receive PRDL or DM, VCR, and ASP in the same manner as VLR patients. Patients also receive DNR IV over 1-4 hours on days 8, 15, 22, and 29 and triple intrathecal therapy (TIT) comprising MTX, cytarabine (ARA-C), and hydrocortisone on days 12 and 25. * AR2 and very high-risk (VHR) patients:Patients receive PRDL or DM, VCR, and ASP in the same manner as VLR patients and high-dose MTX (HD-MTX) IV over 24 hours on day 8; cyclophosphamide (CTX) IV over 1 hour on day 9; DNR IV over 1-4 hours on days 15, 22, and 29; and TIT on days 12 and 25. Patients with VLR, AR1, or AR2 disease after protocol IA proceed to protocol IB, interval therapy, and then protocol II. Patients with VHR disease after protocol IA proceed to the VHR patient protocol. * Protocol IB (for VLR, AR1, or AR2 patients): Patients with precursor B-cell ALL must be in complete remission (CR) and patients with NHL must be in CR or good partial remission. * VLR patients: Patients receive oral mercaptopurine (MP) on days 36-63; ARA-C IV on days 38-41, 45-48, 52-55, and 59-62; and MTX IT on days 38 and 52. * AR1 and AR2 patients: Patients receive oral MP and ARA-C in the same manner as VLR patients; CTX IV over 1 hour on days 36 and 63; and TIT on days 38 and 52. * VLR, AR1, and AR2 patients are also randomized to 1 of 2 treatment arms. * Arm I: Patients receive ASP IV or IM on days 38, 41, 45, 48, 52, 55, 59, and 62. * Arm II: Patients receive no ASP. * Interval therapy for VLR, AR1, or AR2 patients (begins 14 days after completion of protocol I): Patients receive oral MP daily on days 1-56; HD-MTX IV over 24 hours on days 8, 22, 36, and 50; leucovorin calcium (CF) (or levofolinic acid) orally or IV beginning 36 hours after initiation of MTX infusion and repeating every 6 hours until hour 72 or until serum MTX level is adequate; and TIT on days 9, 23, 37, and 51. * Protocol II (reinduction therapy IIA and reconsolidation therapy IIB): * VLR patients: Patients receive oral DM twice daily on days 1-21; VCR IV on days 8, 15, 22, and 29; doxorubicin (DOX) IV over 1-4 hours on days 8 and 15; ARA-C IV on days 38-41 and 45-48; oral thioguanine (TG) once daily on days 36-49; and MTX IT on day 38. * AR patients: Patients receive DM, VCR, ARA-C, and TG in the same manner as VLR patients; DOX IV over 1-4 hours on days 8, 15, 22, and 29; CTX IV over 30-60 minutes on day 36; and TIT on day 38. * VLR and AR patients are also randomized to 1 of 2 treatment arms. * Arm I: Patients receive short-term ASP IV over 1 hour or IM on days 8, 11, 15, and 18. * Arm II: Patients receive long-term ASP IV over 1 hour or IM on days 8, 11, 15, 18, 22, 25, 29, and 32. * Maintenance therapy for VLR and AR patients (begins 14 days after completion of protocol II): * VLR patients: Patients receive oral MP once daily and oral MTX once weekly for a total of 74 weeks. * AR1 patients: Patients receive oral MP once daily on days 1-70; oral MTX on days 1, 8, 15, 29, 36, 43, 50, 57, and 64; and TIT on day 22. Treatment repeats every 10 weeks for 6 courses. * AR2 patients: Patients receive MP and oral MTX (as for AR1 patients); HD-MTX IV over 24 hours on day 22; CF as in interval therapy on days 23 and 24; and TIT and ASP on day 23. After course 6, AR1 and AR2 patients receive further maintenance therapy comprising oral MP once daily and oral MTX once a week. * VHR patient protocol (recommended treatment): Patients with VHR disease after protocol IA receive reinforced consolidation (protocol IB') and VANDA regimens. * Protocol IB': Patients receive oral DM twice daily on days 36-40 and 50-54; oral MP daily on days 36-40; VCR IV on days 36 and 41; HD-MTX IV over 24 hours on days 36 and 50; TIT on days 37 and 51; ARA-C IV over 3 hours every 12 hours on day 40; ASP IV over 1 hour or IM on days 41, 43, 45, 55, 57, and 59; oral TG once daily on days 50-54; vindesine (DAVA) IV on day 50; DNR IV over 1-4 hours on day 54; and CTX IV over 1 hour on days 52 and 53. Patients who achieve CR after protocol IB' proceed to VANDA regimen. * VANDA regimen: Patients receive oral DM twice daily on days 1-5; ARA-C IV over 3 hours every 12 hours on days 1 and 2; mitoxantrone IV over 1 hour on days 3 and 4; etoposide (VP-16) IV over 1 hour on days 3-5; TIT on day 5; and ASP IV or IM on days 7, 9, 11, and 13. After protocol IB' and VANDA, VHR patients who are eligible for stem cell transplantation (SCT) and have an HLA-compatible familial donor undergo transplantation. Patients who are ineligible for SCT receive interval therapy, followed by 2 sequences of blocks R1, R2, and R3 (2 courses of each block for a total of 6 courses), and then maintenance therapy for a total treatment duration of 2 years. * Interval therapy: Patients receive oral MP once daily on days 1-42; HD-MTX IV over 24 hours on days 8, 22, and 36; CF as in interval therapy (described above); and TIT on days 9, 23, and 37. * Blocks R1, R2, and R3 (this sequential regimen is repeated once): * R1: Patients receive oral DM twice daily and oral MP once daily on days 1-5; VCR IV on days 1 and 6; HD-MTX IV over 24 hours on day 1; CF as in interval therapy on days 1 and 2; TIT on day 2; ARA-C IV over 3 hours every 12 hours on day 5; and ASP IV over 1 hour or IM on day 6. * R2: Patients receive DM, HD-MTX, CF, TIT, and ASP as in block R1 and oral TG once daily on days 1-5; DAVA IV on day 1; CTX IV over 1 hour on days 3 and 4; and DNR IV over 1-4 hours on day 5. * R3: Patients receive DM and ASP as in block R1 and ARA-C IV over 3 hours every 12 hours on days 1 and 2; VP-16 IV over 1 hour on days 3-5; and TIT on day 5. * Maintenance therapy: (begins 14 days after the second course of block R3 and ends 2 years after initiation of study therapy): Patients receive treatment as in maintenance therapy for AR1 patients. Treatment repeats every 10 weeks for 5 courses. Patients are followed every 3 months for 5 years and then annually thereafter. PROJECTED ACCRUAL: A total of 1,400-1,500 patients will be accrued for this study within 5.5 years.