Figure 1
Figure 1. Clinical trial schema. Patients received fludarabine 25 mg/m2/day intravenously (IV) daily (days −6 through −2) and cyclophosphamide 60 mg/kg/day IV (days −5 and −4) to lymphodeplete the recipient and facilitate homeostatic expansion of allogeneic NK cells. One (n = 11) or 2 doses (n = 4) of IL2DT, 12 (n = 11) or 18 mg/kg (n = 4) IV, were added at day −1 ± −2 to deplete Treg. NK cell products were administered by IV infusion on day 0 followed by subcutaneous IL-2 (9 × 106 units) starting 4 hours after NK cell infusion and given every other day for 6 doses to facilitate NK cell survival and expansion in vivo. Unseparated PB donor chimerism by STR and lymphocyte subsets were analyzed at days 7, 14, and 28. Bone marrow (BM) was analyzed for leukemia clearance at days 14 and 28 to assess disease status according to World Health Organization criteria. Toxicity and adverse events were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events V 3.0. The primary prospective end point of the study was successful in vivo donor NK cell expansion defined as measurement of >100 donor NK cells/μL of PB at day +14 after NK cell infusion [(absolute lymphocyte count/μL) × (% of lymphocyte gate that are CD56+/CD3− NK cells) × (% donor chimerism using standard short tandem repeat testing)]. We evaluated BM at day 28 and used standard definitions of CR, CRp (<100 000 platelet count/μL), and CRi (<1000 absolute neutrophils/μL).

Clinical trial schema. Patients received fludarabine 25 mg/m2/day intravenously (IV) daily (days −6 through −2) and cyclophosphamide 60 mg/kg/day IV (days −5 and −4) to lymphodeplete the recipient and facilitate homeostatic expansion of allogeneic NK cells. One (n = 11) or 2 doses (n = 4) of IL2DT, 12 (n = 11) or 18 mg/kg (n = 4) IV, were added at day −1 ± −2 to deplete Treg. NK cell products were administered by IV infusion on day 0 followed by subcutaneous IL-2 (9 × 106 units) starting 4 hours after NK cell infusion and given every other day for 6 doses to facilitate NK cell survival and expansion in vivo. Unseparated PB donor chimerism by STR and lymphocyte subsets were analyzed at days 7, 14, and 28. Bone marrow (BM) was analyzed for leukemia clearance at days 14 and 28 to assess disease status according to World Health Organization criteria. Toxicity and adverse events were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events V 3.0. The primary prospective end point of the study was successful in vivo donor NK cell expansion defined as measurement of >100 donor NK cells/μL of PB at day +14 after NK cell infusion [(absolute lymphocyte count/μL) × (% of lymphocyte gate that are CD56+/CD3 NK cells) × (% donor chimerism using standard short tandem repeat testing)]. We evaluated BM at day 28 and used standard definitions of CR, CRp (<100 000 platelet count/μL), and CRi (<1000 absolute neutrophils/μL).

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