Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients

Antonio Curti, Loredana Ruggeri, Alessandra D'Addio, Andrea Bontadini, Elisa Dan, Maria Rosa Motta, Sara Trabanelli, Valeria Giudice, Elena Urbani, Giovanni Martinelli, Stefania Paolini, Fiorenza Fruet, Alessandro Isidori, Sarah Parisi, Giuseppe Bandini, Michele Baccarani, Andrea Velardi, Roberto M. Lemoli

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Abstract

Thirteen patients with acute myeloid leukemia, 5 with active disease, 2 in molecular relapse, and 6 in morphologic complete remission (CR; median age, 62 years; range, 53-73 years) received highly purified CD56 +CD3 - natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/ cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. The median number of infused NK cells was 2.74 × 10 6/Kg. T cells were <10 5/Kg. No NK cell-related toxicity, including GVHD, was observed. One of the 5 patients with active disease achieved transient CR, whereas 4 of 5 patients had no clinical benefit. Both patients in molecular relapse achieved CR that lasted for 9 and 4 months, respectively. Three of 6 patients in CR are disease free after 34, 32, and 18 months. After infusion, donor NK cells were found in the peripheral blood of all evaluable patients (peak value on day 10). They were also detected in BM in some cases. Donor-versus-recipient alloreactive NK cells were shown in vivo by the detection of donor-derived NK clones that killed recipient's targets. Adoptively transferred NK cells were alloreactive against recipient's cells, including leukemia. In conclusion, infusion of purified NK cells is feasible in elderly patients with high-risk acute myeloid leukemia. This trial was registered at www.clinicaltrial.gov as NCT00799799.

Original languageEnglish
Pages (from-to)3273-3279
Number of pages7
JournalBlood
Volume118
Issue number12
DOIs
Publication statusPublished - Sep 22 2011

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Curti, A., Ruggeri, L., D'Addio, A., Bontadini, A., Dan, E., Motta, M. R., Trabanelli, S., Giudice, V., Urbani, E., Martinelli, G., Paolini, S., Fruet, F., Isidori, A., Parisi, S., Bandini, G., Baccarani, M., Velardi, A., & Lemoli, R. M. (2011). Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood, 118(12), 3273-3279. https://doi.org/10.1182/blood-2011-01-329508