Inclusion Criteria:

Group A (adults):

• Adult patients affected by:
  • Acute leukemia (AML, ALL) defined as:
    • Acute Myeloid Leukemia (AML):
    • High risk AML in CR1; any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities
    • Chemo-refractory relapse (MRD+)
    • ≥ CR2
  • Acute Lymphoblastic Leukemia (ALL):
    • Chemo-refractory relapse (MRD+)
    • High risk ALL in CR1; Philadelphia (like) or any poor risk feature
    • ≥ CR2
    • Acute leukemia of ambiguous lineage:
    • ≥ CR1 with a minimal residual disease (MRD) <5% (flow cytometry, molecular and/or cytogenetics accepted)
  • Myelodysplastic Syndrome (MDS) with least one of the following:
  • Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
  • Life-threatening cytopenia.
  • Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
  • Therapy related disease or disease evolving from other malignant processes.
• Patient eligible for a T-depleted allogeneic HSCT
• Age ≥ 18y and clinical condition compatible with allogeneic stem cell transplantation
• Karnofsky index ≥ 70% prior to conditioning regimen
• Patients with normal organ function prior to conditioning regimen

Group B (pediatrics):

• Pediatric patients affected by acute leukemia defined as:
  • Acute Myeloid Leukemia (AML):
    • High risk AML in CR1; any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities,
    • Chemo-refractory relapse (MRD+)
    • ≥ CR2
  • Acute Lymphoblastic Leukemia (ALL):
    • Chemo-refractory relapse (MRD+)
    • High risk ALL in CR1; Philadelphia (like) or any poor risk feature
    • ≥ CR2
  • Acute leukemia of ambiguous lineage:
    • ≥ CR1 with a minimal residual disease (MRD) <5% (flow cytometry, molecular and/or cytogenetics accepted)
• Patient eligible for a T-depleted allogeneic HSCT
• Age < 18y at the time of inclusion
• Absence of a matched sibling donor (MSD)
• Lansky ≥ 70% / Karnofsky performance status ≥ 70% prior to conditioning regimen
• Patients with normal organ function prior to conditioning regimen

Exclusion Criteria:

Groups A and B:

• Use of an HLA matched Cord Blood (8/8 allele matched) or haploidentical donor
• Prior therapy with allogeneic stem cell transplantation
• Treatment with another cellular therapy within one month before inclusion