Trial protocol intended the optimization of induction treatment with:

1. Inclusion of PEG-ASP in induction and in the three blocks of consolidation.
2. Reduction of the dose of daunorubicin, and recent studies have shown that the use of high doses of anthracyclines has not brought higher response rates or longer duration
3. Replacing the poor cytological response at day 14 by the level of ER at the end of induction as a criterion to decide the further treatment (consolidation or second induction), so as to have only one criterion (the ER) throughout the study to decision making.

For another hand, reducing non-essential drugs consolidation blocks to try to reduce toxicity during it, and replace the ASP E. coli in induction and consolidation of PEG-ASP to ensure a more sustained asparagine depletion. Also, increasing the dose of methotrexate (3 to 5 g/m2) in patients with ALL-T, since there is recent evidence of a higher response rate with this strategy.

Performing an allo-HSCT early (after one cycle of consolidation) for patients with inadequate level of ER after two cycles of induction or in those patients who required two courses of induction and have obtained proper ER after the second.

Conducting studies of RD centrally by cytofluorometry following Euroflow consensus standards, to avoid bias in making treatment decisions

Inclusion Criteria:

• ALL de novo high-risk criteria
• Age 15-55 years (55-60 years patients will be included at the discretion of the medical team that will attend)
• No prior treatment, except Emergency leukapheresis Emergency treatment of hyperleukocytosis with hydroxyurea Urgent cranial irradiation (one dose) for CNS leukostasis Mediastinal irradiation for urgent superior vena cava syndrome
• General condition suitable scale (ECOG 0-2), or> 2 if due to ALL
• Negative pregnancy test for women of childbearing age
• Written informed consent because, although the protocol does not include the use of investigational drugs, biological samples sent there for them

Exclusion Criteria:

• L3 type ALL or mature phenotype B (sIg +) or cytogenetic abnormalities characteristic of mature B-ALL (t (8; 14), t (2, 8), t (8; 22)). For these patients is available BURKIMAB protocol.
• LAL Ph (BCR-ABL) positive. For these patients have the protocol ALL-Ph-08 (if under 55) or LALOPh (if over 55).
• Lymphoid blast crisis of chronic myeloid leukemia
• Biphenotypic acute leukemia or bilinear according to the criteria of EGIL group
• Undifferentiated acute leukemias
• Patients with a history of coronary artery disease, valvular or hypertensive heart disease, contraindicating the use of anthracyclines
• Patients with chronic phase of activity
• Patients with severe chronic respiratory failure
• Kidney failure due to ALL
• Serious neurological disorder not due to the LAL
• History of pancreatitis
• Pregnancy or breastfeeding
• Mental or psychiatric illness preventing informed consent is given for sending samples or properly follow the study
• General condition affected, not attributable to the ALL

ALL patients