The primary objective of this trial is to improve the overall survival rate of children and young adult with B-lineage acute lymphoblastic leukemia (B-ALL) in Singapore and Malaysia in the context of a multicenter cooperative trial using a risk-stratified therapy.

This is a multicenter open-label phase II study involving children and young adult (< 41 years old) who are newly diagnosed with B-ALL and treatment naïve. There will be 3 parallel cohorts whose risk to be stratified based upon leukemia genetics profiles and patient's treatment response:

1. Standard Risk (SR)
2. Intermediate Risk (IR)
3. High Risk (HR)

All drugs being used are commercially available chemotherapy drugs. There will be no novel chemotherapeutic agent without marketing authorization being tested in this trial.

Inclusion Criteria:

1. Has been diagnosed with B-lineage ALL as evidenced by:

   1. BMA blasts > 20% AND
   2. Leukemic process in the bone marrow, peripheral blood or any extra medullary tissue with confirmation of B-lymphoid differentiation by flow immunophenotyping or histopathologically

2. Age < 41 years of age at enrolment

3. Written informed consent obtained from patient or legally acceptable representative (LAR)

Exclusion Criteria:

1. T-lineage ALL
2. Down syndrome with ALL
3. History of previous malignancies or this ALL is a second malignancy
4. Mixed phenotype acute leukemia (MPAL) or undifferentiated leukemia
5. Mature B-cell leukemia/lymphoma
6. Any previous cytotoxic therapy (chemotherapy/radiotherapy/immunotherapy). Patient pre-treated with short term steroid (< 7 days of duration within last 1 month prior to ALL treatment start) may be enrolled after discussion and written approval from PI. These patients should be treated on at least intermediate arm.
7. Persistent renal dysfunction with creatinine more than upper limit of normal for age before start of induction therapy. Patients requiring temporary dialysis without persistent renal dysfunction can qualify.
8. Liver dysfunction with direct bilirubin > 10x upper normal limit for age.
9. Any serious uncontrolled medical condition or impending end organ dysfunction that would impair the ability of the subject to receive protocol therapy
10. Doubtful compliance or ability to complete study therapy due to financial, social, familial or geographic reason, or in the judgement of site investigator