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

• Published in: Biology of blood and marrow transplantation 2016-04, Vol.22 (4), p.705-709
• Main Authors: Shaffer, Brian C, Le Luduec, Jean-Benoit, Forlenza, Christopher, Jakubowski, Ann A, Perales, Miguel-Angel, Young, James W, Hsu, Katharine C
• Format: Article
• Language: English
• Subjects: Adult; Allogeneic transplantation; AML; Busulfan - therapeutic use; Child; Child, Preschool; Cyclophosphamide - therapeutic use; Female; Gene Expression; Graft vs Host Disease - immunology; Graft vs Host Disease - mortality; Graft vs Host Disease - pathology; Graft vs Host Disease - prevention & control; Haplotypes; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents - therapeutic use; Infant; Interleukin-2 - therapeutic use; Killer Cells, Natural - immunology; Killer Cells, Natural - transplantation; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; Male; MDS; Middle Aged; Myeloablative Agonists - therapeutic use; Myelodysplastic Syndromes - immunology; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - pathology; Myelodysplastic Syndromes - therapy; Natural killer cell; Receptors, Natural Killer Cell - genetics; Receptors, Natural Killer Cell - immunology; Recurrence; Sialic Acid Binding Ig-like Lectin 3 - genetics; Sialic Acid Binding Ig-like Lectin 3 - immunology; Siblings; Survival Analysis; Transplantation Conditioning - methods; Transplantation, Homologous
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2015.12.028

Abstract 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.