The purpose of this study is to reduce the side-effects from anti-leukemia therapy. The therapy in this study is based upon treatment information learned from prior clinical research programs as well as from laboratory research.

• Children with acute lymphoblastic leukemia are treated somewhat differently depending on the relative risk of the leukemia recurring. Patients will be separated into "Standard Risk" and "High Risk".
• The treatment program for both groups is separated into 4 phases. The phases of treatment are induction, central nervous system (CNS) therapy, intensification and continuation.
• The induction phase of therapy lasts for about one month and its purpose is to kill all detectable leukemia cells. Patients in both groups will receive the following medication: prednisone, vincristine, doxorubicin, methotrexate, leucovorin, asparaginase, cytarabine (ARA-C), and hydrocortisone. Patients in the "Hight Risk" group will also receive dexrazoxane.
• Patients whose leukemia is found to have a specific genetic abnormality involving a gene on chromosome 11 (known as MLL gene) will have a MLL intensification phase which begins after complete remission and lasts about 1 month. The drugs involved in MLL intensification are: vincristine, methotrexate, leucovorin, hydrocortisone, cytarabine and L-asparaginase.
• CNS therapy begins immediately after the end of induction therapy, after remission is documented. This phase of treatment should last 3 weeks and includes a series of spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be performed over a two-week period. Both groups will receive vincristine, 6-mercaptopurine and methotrexate/cytarabine/hydrocortisone. Patients in the "High Risk" group will also receive doxorubicin with dexrazoxane.
• Radiation therapy will also be delivered to patients in the "High Risk" group during the CNS therapy phase. Radiation will be given in 8 daily treatments. The total dose of radiation used during this study is lower than what has been used in the past to help reduce side effects without increasing the risk of relapse.
• The intensification phase begins after the CNS therapy ends and lasts for 30 weeks. This phase is intended to further reduce the number of leukemia cells in the body and consists of cycles of chemotherapy repeated every three weeks with weekly shots of asparaginase. The drugs administered to both groups during this phase are: prednisone or dexamethasone, vincristine,6-mercaptopurine, methotrexate, E. coli asparaginase and cytarabine. Patients in the "High Risk" group will also receive doxorubicin and dexrazoxane.
• The continuation phase begins after the completion of the intensification phase and the goal is to eradicate all leukemia from the body. It consists of cycles of chemotherapy repeated every 3 weeks and is continued until the patient has been in remission for 2 years. The drugs administered during this phase are vincristine, prednisone or dexamethasone, 6-mercaptopurine, methotrexate and cytarabine.
• During this trial there are two randomizations, each is between the "standard" treatment and the "investigational" treatment. One randomization involves the drug E. coli L-asparaginase and two ways of dosing this drug. One way is to give the same standard dose of the drug that has been administered for years. The other way is to start with a lower dose and measure the amount of the drug in the blood every 3 weeks adjusting the dose as necessary. The goal of doing this is to maintain adequate drug levels with lower doses in the hope the it may reduce some side effects of the drug.
• The second randomization involves the drugs prednisone and dexamethasone. Both drugs have been used in the past to help treat ALL but it is not known if there is a difference between the two drugs, especially in terms of side effects. Patients will be randomized to either receive dexamethasone or prednisone.
• Throughout the study blood tests, urine tests, spinal taps, and bone marrow tests will be performed to monitor the disease status, side effects from medications and other complications from therapy.
• Quality of life questionnaires will also be performed by the patient (if older than 8), parent and patient's clinician.

Inclusion Criteria:

• Acute lymphoblastic leukemia excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14) (q24;q32), t(8;22) or t(2;8)
• Age > 12 months but less than 18 years

Exclusion Criteria:

• Prior therapy except, 1 week of steroids, or emergent radiation therapy to the mediastinum
• Known HIV positive