Phase II study of haploidentical natural killer cell infusion for treatment of relapsed or persistent myeloid malignancies following allogeneic hematopoietic cell transplantation Journal Article


Authors: Shaffer, B. C.; Le Luduec, J. B.; Forlenza, C.; Jakubowski, A. A.; Perales, M. A.; Young, J. W.; Hsu, K. C.
Article Title: Phase II study of haploidentical natural killer cell infusion for treatment of relapsed or persistent myeloid malignancies following allogeneic hematopoietic cell transplantation
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. © 2016 American Society for Blood and Marrow Transplantation.
Keywords: natural killer cell; allogeneic transplantation; aml; mds
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 22
Issue: 4
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2016-04-01
Start Page: 705
End Page: 709
Language: English
DOI: 10.1016/j.bbmt.2015.12.028
PROVIDER: scopus
PMCID: PMC4801764
PUBMED: 26772158
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Miguel-Angel Perales
    378 Perales
  2. Katharine C Hsu
    136 Hsu
  3. James W Young
    257 Young
  4. Brian Carl Shaffer
    45 Shaffer