Inclusion Criteria:

- All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening
(Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement
for B-LLy patients. B-LLy patients may directly enroll on AALL1731.

- Age at diagnosis:

- Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).

- Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).

- Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or
without DS).

- B-ALL patients without DS must have an initial white blood cell count < 50,000/uL
(performed within 7 days prior to enrollment).

- B-ALL patients with DS are eligible regardless of the presenting white blood cell
count (WBC) (performed within 7 days prior to enrollment).

- Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on
a bone marrow (BM) aspirate;

- OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis
can be established by a pathologic diagnosis of B-ALL on a BM biopsy;

- OR a complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells;

- OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without
Down syndrome.

- Note: For B-LLy patients with tissue available for flow cytometry, the criterion
for diagnosis should be analogous to B-ALL. For tissue processed by other means
(i.e., paraffin blocks), the methodology and criteria for immunophenotypic
analysis to establish the diagnosis of B-LLy defined by the submitting
institution will be accepted (diagnostic biopsy for B-LLy must be performed
within 14 days prior to enrollment).

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.

- All patients and/or their parents or legal guardians must sign a written informed
consent.

Exclusion Criteria:

- Patient must not have secondary ALL that developed after treatment of a prior
malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior
history of transient myeloproliferative disease (TMD) are not considered to have had a
prior malignancy. They would therefore be eligible whether or not the TMD was treated
with cytarabine.

- With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1731.

- For patients receiving steroid pretreatment, the following additional exclusion
criteria apply:

- Non-DS B-ALL patients must not have received steroids for more than 24 hours in
the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to
initiation of the steroids.

- DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV
steroids within 4 weeks of diagnosis.

- Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to
the start of systemic protocol therapy.

- B-ALL patients who do not have sufficient diagnostic bone marrow submitted for
APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.

- Patient must not have acute undifferentiated leukemia (AUL).

- Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be
known prior to enrollment).

- Note: DS patients with CNS3 disease are eligible but will be assigned to the
DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior
to administration of any systemic or intrathecal chemotherapy, except for steroid
pretreatment.

- Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular
disease are eligible but will be assigned to the DS-High B-ALL arm).

- For LLy patients, the following additional exclusion criteria apply:

- T-Lymphoblastic Lymphoma.

- Morphologically unclassifiable lymphoma.

- Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.

- CNS positive disease or testicular involvement.

- M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.

- Patients with known Charcot-Marie-Tooth disease.

- Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.

- Patients requiring radiation at diagnosis.

- Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.

- Lactating females who plan to breastfeed their infants.

- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.