Article

NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia.

Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-2794, USA.
Journal of Clinical Oncology (impact factor: 18.37). 02/2010; 28(6):955-9. DOI:10.1200/JCO.2009.24.4590 pp.955-9
Source: PubMed

ABSTRACT PURPOSE To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). PATIENTS AND METHODS Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day -7) and fludarabine (25 mg/m(2)/d on days -6 through -2), followed by killer immunoglobulin-like receptor-human leukocyte antigen (KIR-HLA) mismatched NK cells (median, 29 x 10(6)/kg NK cells) and six doses of interleukin-2 (1 million U/m(2)). NK cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). CONCLUSION Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML.

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Keywords

2-year event-free survival estimate
 
21 years old
 
acute myeloid leukemia
 
AML
 
CONCLUSION Low-dose immunosuppression
 
consolidation therapy
 
days -6
 
donor-recipient inhibitory KIR-HLA mismatched NK cells
 
functional assays
 
haploidentical natural killer
 
Haploidentical Natural Killer Cell Transplantation
 
immunosuppressive regimen
 
killer immunoglobulin-like receptor-human leukocyte antigen
 
KIR-mismatched NK cells
 
median follow-up time
 
Median length
 
NK cell chimerism
 
Nonhematologic toxicity
 
phase II trial
 
significant expansion