Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

Inclusion Criteria: * AML patients * Diagnosis of AML with indication to allogeneic hematopoietic cell transplantation. * Diagnosis of adverse genetic risk leukemia or presence of MRD or active disease (bone marrow infiltration 5-30%) at the time of the transplant procedure. * Availability of a hematopoietic stem cell donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses. * Age ≥ 18 and ≤ 65 years * ECOG ≤ 2 * HCT-CI ≤ 4 (51,52) * Absence of relevant psychiatric diseases * Signature of the informed consent ALL patients * Diagnosis of ALL, either T or B (Philadelphia negative) or mixed phenotype with indication to allogeneic transplant * Presence of MRD or active disease (bone marrow infiltration 5-30%) or patient with ≥ 2nd complete hematologic remission at the time of the transplant procedure. * Availability of a hematopoietic stem cell family donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses. * Age ≥ 18 and ≤ 65 years * ECOG ≤ 2 * HCT-CI ≤ 4 * Absence of relevant psychiatric diseases * Signature of the informed consent Exclusion Criteria: * AML patients * AML in CR MRD- * AML with \> 5% peripheral blasts or bone marrow infiltration ≥ 30% * Age \< 18 years or \> 65 years * ECOG \> 2 * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment * Pregnancy * No signature of the informed consent * ALL patients * ALL with \> 5% peripheral blasts or bone marrow infiltration ≥30% * Philadelphia positive ALL * Age \< 18 years or \> 65 years * ECOG \> 2 * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment * Pregnancy * No signature of the informed consent