Phase II Study of Haploidentical Natural Killer Cell Infusion for Treatment of Relapsed or Persistent Myeloid Malignancies Following Allogeneic Hematopoietic Cell Transplantation

•Haploidentical NK cells were administered to allogeneic HCT recipients.•Responses were seen in 3 of 8 treated patients with relapsed malignancy.•No patient developed graft-versus-host disease.•Haploidentical NK cells did not persist despite immunocompromised recipients.

We conducted a phase 2 study to determine the efficacy of HLA-haploidentical related donor natural killer (NK) cells after cyclophosphamide-based lymphodepletion in patients with relapsed or progressive acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) following allogeneic hematopoietic cell transplantation (HCT). Eight patients (2 with MDS and 6 with AML) were treated with cyclophosphamide 50 mg/kg on day −3 and day −2 before infusion of NK cells isolated from a haploidentical related donor. One patient also received fludarabine 25 mg/m2/day for 4 days. Six doses of 1 million units of interleukin-2 (IL-2) were administered on alternating days beginning on day −1. The median number of NK cells infused was 10.6 × 106/kg (range, 4.3 to 22.4 × 106/kg), and the median number of CD3 cells infused was 2.1 × 103/kg (range, 1.9 to 40 × 103/kg). NK infusions were well tolerated, with a median time to neutrophil recovery of 19 days (range, 7 days to not achieved) and no incidence of graft-versus-host disease after NK infusion. One patient with AML and 1 patient with MDS achieved a complete response, but relapsed at 1.7 and 1.8 months, respectively. One patient with MDS experienced resolution of dysplastic features but persistence of clonal karyotype abnormalities; this patient was stable at 65 months after NK cell therapy. The median duration of survival was 12.9 months (range, 0.8 to 65.3 months). Chimerism analysis of CD3−/CD56+ peripheral blood cells did not detect any circulating haploidentical NK cells after infusion. NK phenotyping was performed in 7 patients during and after IL-2 infusion. We found a slight trend toward greater expression of KIR2DL2/2DL3/2DS2 (5% versus 28%; P = .03) at 14 days in patients who survived longer than 6 months from NK cell infusion (n = 4) compared with those who died within 6 months of NK cell therapy (n = 3). In summary, our data support the safety of haploidentical NK cell infusion after allogeneic HCT.