Irradiation-based Myeloablative Conditioning Followed by Treg/Tcon Immunotherapy in HSCT

Antileukemic Activity of Allogeneic Hematopoietic Stem Cell Transplantation With Fractionated Total Body Irradiation or Total Marrow and Lymph Node Irradiation Followed by Adoptive Immunotherapy With Regulatory and Conventional T Cells

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