Despite anti-thymocyte globulin has a mainstay role in preventing GvHD (and non-relapse mortality) in CB transplantation, it also induces delayed immune recovery, increased risk of cytomegalovirus and Epstein-Barr virus reactivation, post-transplant lymphoproliferative diseases, overall accounting for increased transplant-related mortality and/or increased relapse incidence. All these findings support the use of alternative approaches for in vivo T cell depletion in the setting of CB transplantation.

Study objectives. The primary objective is to evaluate neutrophil and platelet engraftment and day +100 CD4+ cell count in patients receiving matched CB unit transplant with a myeloablative conditioning regimen and a GVHD prophylaxis including post-transplant cyclophosphamide. Secondary objective is to estimate the incidence and severity of acute and chronic GVHD. Study endpoints. Primary endpoints are hematopoietic engraftment and day +100 CD4+ cell count. Secondary endpoints are acute and chronic GVHD

Inclusion Criteria:

• Age: ≥ 18 ≤ 75 years old
• CB unit transplantation (TNC> 2,0 x10^7/kg and > 4/6 loci HLA matched)
• Myeloablative conditioning regimen consisting of either Thiotepa/ Busulfan/ Fludarabine or TBI/ Fludarabine
• GVHD prophylaxis including PT-Cy (30 mg/kg or more on days + 3and +5) CSA and MMF
• Diagnosis of 1 of the following hematological malignancies: Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome, high risk Acute Lymphoblastic Leukemia (ALL), Bi phenotypic/undifferentiated leukemia, Chronic Myeloid Leukemia resistant to TK inhibitors, Ph-neg Myeloproliferative Neoplasms, resistant/relapsing Non-Hodgkin's lymphoma ineligible for an autologous transplant.

Exclusion Criteria:

• Positive serologic markers for human immunodeficiency virus (HIV)
• Acute hepatitis B virus (HBV) or acute hepatitis C virus (HCV) infection

Patients with no matched (<7/8 HLA loci) sibling or unrelated donor, candidate to receive a transplant of a matched CB unit (TNC> 2,0 x10^7/kg and > 4/6 loci HLA)