An "intention-to-treat" study to evaluate the impact of allogeneic HSCT with Total Marrow and Lymphoid irradiation (TMLI), followed by Treg/Tcon adoptive immunotherapy, on overall survival in patients affected by Myelodysplastic Syndrome (MDS), according to IPSS-R.

MDS patients with Intermediate, High, or Very-High R-IPSS risk will be enrolled. Allogeneic stem cell transplantation with regulatory and conventional T cell adoptive immunotherapy will be proposed to eligible High and Very-High risk MDS patients. Intermediate risk MDS patients will be assessed for risk modification every six months and moved to transplant in case of increased risk. Intermediate risk MDS patients will be also evaluated for the presence of molecular alterations (TP53, ASXL1, RUNX1). Overall survival of the entire cohort will be assessed as primary endpoint. Incidence of Treatment Related Mortality, acute Graft versus Host Disease, chronic Graft versus Host Disease, Relapse will be also assessed.

Inclusion Criteria:

• Patients affected by Myelodysplastic Syndrome with IPSS-R INT, HIGH or VERY HIGH;
• Age <71 years;
• Signature of the informed consent.

Exclusion Criteria:

• Patients affected by Myelodysplastic Syndrome with IPSS-R VERY LOW or LOW;
• Patients affected by Myelodysplastic Syndrome/Myeloproliferative Neoplasm;
• Age >70 years;
• No signature of the informed consent