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

Research output: Contribution to journalArticle

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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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Acute Myeloid Leukemia
Natural Killer Cells
Ligands
KIR Receptors
Tissue Donors
Chemotherapy
T-cells
Immunosuppressive Agents
Cyclophosphamide
Interleukin-2
Toxicity
Blood
Recurrence
Leukemia
Clone Cells
T-Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. / Curti, Antonio; Ruggeri, Loredana; D'Addio, Alessandra; Bontadini, Andrea; Dan, Elisa; Motta, Maria Rosa; Trabanelli, Sara; Giudice, Valeria; Urbani, Elena; Martinelli, Giovanni; Paolini, Stefania; Fruet, Fiorenza; Isidori, Alessandro; Parisi, Sarah; Bandini, Giuseppe; Baccarani, Michele; Velardi, Andrea; Lemoli, Roberto M.

In: Blood, Vol. 118, No. 12, 22.09.2011, p. 3273-3279.

Research output: Contribution to journalArticle

Curti, A, Ruggeri, L, D'Addio, A, Bontadini, A, Dan, E, Motta, MR, Trabanelli, S, Giudice, V, Urbani, E, Martinelli, G, Paolini, S, Fruet, F, Isidori, A, Parisi, S, Bandini, G, Baccarani, M, Velardi, A & Lemoli, RM 2011, 'Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients', Blood, vol. 118, no. 12, pp. 3273-3279. https://doi.org/10.1182/blood-2011-01-329508
Curti, Antonio ; Ruggeri, Loredana ; D'Addio, Alessandra ; Bontadini, Andrea ; Dan, Elisa ; Motta, Maria Rosa ; Trabanelli, Sara ; Giudice, Valeria ; Urbani, Elena ; Martinelli, Giovanni ; Paolini, Stefania ; Fruet, Fiorenza ; Isidori, Alessandro ; Parisi, Sarah ; Bandini, Giuseppe ; Baccarani, Michele ; Velardi, Andrea ; Lemoli, Roberto M. / Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. In: Blood. 2011 ; Vol. 118, No. 12. pp. 3273-3279.
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AU - Curti, Antonio

AU - Ruggeri, Loredana

AU - D'Addio, Alessandra

AU - Bontadini, Andrea

AU - Dan, Elisa

AU - Motta, Maria Rosa

AU - Trabanelli, Sara

AU - Giudice, Valeria

AU - Urbani, Elena

AU - Martinelli, Giovanni

AU - Paolini, Stefania

AU - Fruet, Fiorenza

AU - Isidori, Alessandro

AU - Parisi, Sarah

AU - Bandini, Giuseppe

AU - Baccarani, Michele

AU - Velardi, Andrea

AU - Lemoli, Roberto M.

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N2 - 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.

AB - 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.

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