The goal of this trial is to provide a protocol for treatment for adults with Ph-negative acute lymphoblastic leukemia (ALL) and to learn if this provides higher probability of survival than the previous one. The main question is to know if the incorporation of blinatumomab for B-cell precursor ALL, substituting some chemotherapy blocks, offers better probability of survival than the previous trial, which did not use immunotherapy. In addition, T-cell precursor ALL participants will receive different treatment approaches depending on the stage of maturation of the tumor.

Participants will be uniformly treated with four drug-induction: vincristine (VCR), prednisone (PDN), pegylated asparaginase (PegASP), daunorubicin (DNR).

Resistant participants will receive a second induction with inotuzumab for B-cell precursor ALL or with FLAG-Ida (fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor) for T-cell precursor ALL.

B-cell precursor ALL participants with adequate MRD clearance after cycle 1 of blinatumomab will receive 3 blocks of early consolidation. If adequate MRD clearance and good genetic background, the patients will proceed to delayed intensification, reinduction and maintenance. The remaining patients will receive early or delayed alloHSCT.

T-cell precursor ALL participants with adequate MRD clearance after the first cycle of consolidation will receive 2 blocks of early consolidation and reinduction. If adequate MRD clearance and good genetic background, the patients will proceed to delayed intensification and maintenance. The remaining patients will receive early or delayed alloHSCT.

Inclusion Criteria:

• De novo ALL.
• Age 18-65 years.
• No prior treatment, except:

Urgent leukapheresis, Urgent treatment of hyperleukocytosis with hydroxyurea, Urgent cranial irradiation (one dose) for CNS leukostasis, Urgent mediastinal irradiation for superior vena cava syndrome.

• Adequate general condition (ECOG score 0-2), or >2 if due to ALL.
• Negative pregnancy test for women of childbearing age.

Exclusion Criteria:

• Age > 65 years.
• ALL type L3 or with mature B phenotype (sIg+) or with the cytogenetic alterations characteristic of mature B-cell ALL (t(8;14), t(2;8), t(8;22)).
• Ph-positive B-cell ALL (BCR::ABL1).
• Lymphoid blast crisis of chronic myeloid leukemia.
• Patients with a history of coronary artery disease, valvular heart disease, or hypertensive heart disease, which contraindicates the use of anthracyclines.
• Patients with active chronic liver disease.
• Patients with severe chronic respiratory failure.
• Renal insufficiency not due to ALL.
• Severe neurological disorders, not due to ALL, that contraindicate the use of these treatments (especially blinatumomab).
• History of clinically significant pancreatitis, at the investigator's discretion (taking into account the date of the pancreatitis, its previous severity, and sequelae).
• Pregnancy or breastfeeding.
• Psychiatric or mental illness that prevents providing informed consent for sample submission or adequately participating in the study.
• Impaired general health (ECOG scores 3 and 4) not attributable to ALL.