Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents

Inclusion Criteria:

1. Confirmed diagnosis of acute lymphoblastic leukemia. Diagnosis should be made bybone marrow aspirate or biopsy demonstrating ≥ 25% involvement by lymphoblasts, withflow cytometry or immunohistochemistry confirming B-precursor or T-ALL phenotype.

-- For patients with circulating blasts in the peripheral blood, flow cytometryconfirmation of B-ALL or T-ALL phenotype is sufficient for registration onto thestudy. Bone marrow aspirate and/or biopsy should be performed as soon as feasible,preferably prior to the initiation of any therapy.

2. Prior Therapy: No prior therapy is allowed except for the following:

• Corticosteroids: Short courses of corticosteroid (defined as ≤ 7 days ofcorticosteroids within the 4-weeks preceding registration) are allowed prior toregistration. --- Participants who have been on corticosteroids chronically (defined as morethan 7 days of corticosteroids within the 4-weeks preceding registration ormore than 28 days of corticosteroids over the preceding 6 months) are noteligible.

• IT cytarabine: A single dose of intrathecal cytarabine (at the time of thediagnostic lumbar puncture) is allowed prior to registration. If patient hasreceived IT cytarabine prior to registration, Day 1 IT cytarabine should not beadministered.

• Emergent Radiation Therapy: Emergent radiation to the mediastinum or otherlife-threatening masses is allowed prior to registration.

3. Age: 365 days to < 22 years

4. Direct bilirubin < 1.4 mg/dL (23.9 micromoles/L).

5. Ability of parent or guardian to understand and the willingness to sign a writteninformed consent document.

Exclusion Criteria:

1. Mature B-cell (Burkitt's) ALL (defined by the presence of surface immunoglobulinand/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-generearrangement).

2. World Health Organization diagnostic criteria of mixed phenotype acute leukemia (MPAL) or leukemia of ambiguous lineage

3. Any chemotherapy or radiotherapy for previous malignancy are not eligible.

4. Treatment in past with any anti-neoplastic agent, including methotrexate, 6-mercaptopurine, 6-thioguanine, vincristine cyclophosphamide, cytarabine (exceptfor IT cytarabine), or any anthracycline, for any reason (eg, rheumatologic orautoimmune condition).

5. Currently receiving any investigational agents.

6. Known HIV-positivity

7. Uncontrolled intercurrent illness including, but not limited to ongoing infectionwith vital sign instability (hypotension, respiratory insufficiency),life-threatening acute tumor lysis syndrome (eg, with renal failure), symptomaticcongestive heart failure, cardiac arrhythmia, intracranial or other uncontrolledbleeding, or psychiatric illness/social situations that would limit compliance withstudy requirements.

8. Pregnant women are excluded from this study because many of the agents used on thisprotocol have potential for teratogenic and/or abortifacient effects. Because thereis an unknown but potential risk of adverse events in nursing infants secondary totreatment of the mother with these chemotherapy agents, breastfeeding should bediscontinued if the mother is enrolled.

9. History of a previous malignancy. Exception: Individuals with a previous malignancytreated with surgery only (no chemotherapy or radiotherapy) more than 5 years priorto registration may be enrolled.