On day 0, patients will receive a fixed dose of 1.0-3.0 x 10^9 allogeneic UCB-NK cells. Prior to NK cell infusion, patients will receive cyclophosphamide and fludarabine (Cy/Flu) based lymphodepleting chemotherapy. NK cells administration will not be followed by sc IL-2. N=3.

On day 0, patients will receive a fixed dose of 1.0-3.0 x 10^9 allogeneic UCB-NK cells. Prior to NK cell infusion, patients will receive cyclophosphamide and fludarabine (Cy/Flu) based lymphodepleting chemotherapy. IL-2 will be administered in a fixed dose of 3.0 x 10^6 units starting 4 hours after NK cell infusion and given every other day for 6 doses in total. N=3

On day 0, patients will receive a fixed dose of 1.0-3.0 x 10^9 allogeneic UCB-NK cells. Prior to NK cell infusion, patients will receive cyclophosphamide and fludarabine (Cy/Flu) based lymphodepleting chemotherapy. IL-2 will be administered in a fixed dose of 6.0 x 10^6 units starting 4 hours after NK cell infusion and given every other day for 6 doses in total. N=6

Natural killer cells generated from CD34+ hematopoietic progenitor cells derived from an allogeneic umbilical cord blood

Patients will be evaluated intensively using the CTCAE toxicity criteria and graft versus host disease (GvHD) classification criteria, defining dose limiting toxicities (DLTs): 1. Any treatment-emergent non-hematologic grade 3 toxicity lasting >72 hours, except for transient constitutional symptoms, diarrhea, fatigue or skin rash not requiring systemic steroid therapy. 2. Acute GvHD >grade 2 within 6 weeks of the first IL-2 dose. If in any of the three patients of each individual cohort of the phase I study a DLT occurs, the cohort will be extended to 6 patients. If 2 patients experience DLT within a cohort of 3 or 6 patients the study will be stopped in case the patients were only receiving NK cells or the study will be continued without IL-2 or the lower dose of IL-2 in case the patients were receiving NK cells in combination with IL-2. Serious, life threatening adverse events or grade 4 toxicity will be a reason to terminate the study or continue without IL-2 cytokine support.

The primary objective of phase IIa of the study is to evaluate the effect of UCB-NK cell adoptive immunotherapy in combination with SC IL-2 following a non-myeloablative immunosuppressive conditioning regime on disease activity in patients with AML. At day 28 a bone marrow biopsy will be performed to evaluate % blasts or % minimal residual disease (MRD) in the bone marrow. A complete remission is defined as BM blasts <5%; marrow should not be merely 'aplastic': at least 200 cells should be enumerated or cellularity should be at least 10%. MRD will be evaluated by flow cytometry (leukemia associated phenotypes (LAPs)) and/or molecular quantification of patient specific mutations (PCR).

For phase IIa of the study the clinical evaluation data (% blasts and % MRD positivity) will be translated in a clinical response (stable disease, partial remission, complete remission) and quantitative presented.

We will determine the percentage and absolute number of donor-derived NK cells in peripheral blood and bone marrow after infusion using flow cytometry and DNA chimerism analysis. A positive expansion rate of the infused NK cells requires an absolute number of ≥100 donor-derived NK cells per μl blood at day +7 and/or +14.