To evaluate if hyper-fractionated TBI or TMLI followed by Treg/Tcon adoptive immunotherapy improve cGvHD/disease free survival after allogeneic HSCT in patients affected by high-risk acute leukemias or other hematologic malignancy where HSCT is indicated.

Improving cGvHD/disease free survival in patients with high-risk acute leukemias or other hematologic malignancy where HSCT is indicated with the use of a regulatory T cell based protocol. Hyper-fractionated Total Body Irradiation or Total Marrow and Lymphoid Irradiation based conditioning will be followed by the infusion of T regulatory and T conventional cell adoptive immunotherapy and a purified CD34+ hematopoietic stem cell graft. Incidence of Non Relapse Mortality, Relapse, acute Graft versus Host Disease, chronic Graft versus Host Disease, as well as probability of cGvHD/disease free survival will be assessed in patient subpopulations separated according to HLA-matching with the donor (HLA-matched HSCT and HLA-haploidentical HSCT) and type of disease (acute myeloid leukemia, acute lymphoid leukemia, lymphoma, multiple myeloma, myeloproliferative disease, and other).

Inclusion Criteria:

• AML and ALL in complete remission and with high-risk of relapse

• AML and ALL primarily chemoresistant or relapsed;

• Chronic Myeloid Leukemia in accelerated or blastic phase;

• Patients affected by

  • Multiple myeloma,
  • Non Hodgkin lymphoma,
  • Hodgkin lymphoma,
  • Chronic myeloproliferative syndrome,
  • Chronic Lymphoid Leukemia,
  • Other Hematological malignancy at high-risk of relapse or detectable disease and where a HSCT is indicated.

• Age <75 years

• ECOG ≤ 2

• Acceptable lung, liver, kidney, and heart function and absence of relevant psichiatric diseases

• Signature of the informed consent

Exclusion Criteria:

• Age >75 years
• ECOG > 2
• Not acceptable lung, liver, kidney, and heart function and presence of relevant psichiatric diseases
• Pregnancy
• No signature of the informed consent