Purpose of the study

        1. For slow early responder (SER), to confirm if the augmented interim maintenance using
           intravenous high dose methotrexate will improve the treatment outcome.

        2. For slow early responder (SER), to confirm if removal of prophylactic radiotherapy will
           relieve long term complications.

        3. To predict the treatment response and prognosis high risk pediatric ALL by monitoring of
           minimal residual disease (MRD).

      Inclusion criteria

      1. Diagnosis

        1. Newly diagnosed B-precursor ALL meeting criteria 1.2

        2. Newly diagnosed B-precursor ALL who was previously treated with steroid.

        3. Newly diagnosed T cell ALL, excluding early T-cell precursor (ETP) leukemia

      1.2 Initial WBC count

        1. from 1 years old to 9 years old : WBC ≥ 50,000/μL

        2. from 10 years old to 21 years old : Any WBC

        3. from 1 years old to 21 years old : Any WBC with Testicular leukemia or CNS leukemia
           (CNS3)

      Exclusion criteria (who are classified as very high risk group) 2.1 Philadelphia chromosome
      (+) or bcr/abl rearrangement (+) 2.2 Chromosome <45 by cytogenetics 2.3 Induction failure
      (Day 28 M3 marrow (>25% blasts)) 2.4 t(4:11) (as identified by cytogenetics, FISH or
      molecular studies) 2.5 Early T-cell precursor leukemia 2.6 Down syndrome ALL

      Methods We will classify the patients to rapid early responder (RER) and slow early responder
      (SER), according to the treatment response after induction remission and risk factors at
      diagnosis. SER includes M2 (5-25% or leukemic cells at bone marrow exam) or M3 (25% or more
      of leukemic cells at bone marrow exam) response at the 14th day of the start of induction
      remission. If a patient showed total WBC count ≥ 100,000/μL, had testis or CNS (CNS 3)
      involvement at diagnosis and was diagnosed as T-ALL, the patients will also be included into
      the SER group.

      Rapid early responders will undergo interim maintenance two times and reinduction for one
      time. Slow early responders will undergo two times of interim maintenance treatment with high
      dose intravenous methotrexate. For SER, adriamycin was previously administered only when
      absolute neutrophil count and platelet was normal, but it will be administered without
      restriction in this study. Both groups (RER and SER) will undergo maintenance chemotherapy
      thereafter, with the treatment duration of 3 years from the 1st interim maintenance for boys
      and 2 years for girls.

      For SER group, prophylactic radiotherapy will not be done and it will be replaced by high
      dose intravenous methotrexate and intensification of intrathecal chemotherapy by replacing
      the intrathecal methotrexate to intrathecal cytarabine, methotrexate and hydrocortisone.