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 and MUST submit eligibility studies. - 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. - 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 evidence of a MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype. - 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.