Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients

Antonio Curti, Loredana Ruggeri, Sarah Parisi, Andrea Bontadini, Elisa Dan, Maria Rosa Motta, Simonetta Rizzi, Sara Trabanelli, Darina Ocadlikova, Mariangela Lecciso, Valeria Giudice, Fiorenza Fruet, Elena Urbani, Cristina Papayannidis, Giovanni Martinelli, Giuseppe Bandini, Francesca Bonifazi, Russell E. Lewis, Michele Cavo, Andrea VelardiRoberto M. Lemoli

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Abstract

Purpose: In acute myeloid leukemia (AML), alloreactive natural killer (NK) cells are crucial mediators of immune responses after haploidentical stem cell transplantation. Allogeneic NK cell infusions have been adoptively transferred with promising clinical results. We aimed at determining whether the composition of NK graft in terms of frequency of alloreactive NK cells influence the clinical response in a group of elderly AML patients undergoing NK immunotherapy. Experimental Design: Seventeen AML patients, in first complete remission (CR; median age 64 years, range 53-73) received NK cells from haploidentical KIR-ligand-mismatched donors after fludarabine/cyclophosphamide chemotherapy, followed by IL2. To correlate donor NK cell activity with clinical response, donor NK cells were assessed before and after infusion. Results: Toxicity was moderate, although 1 patient died due to bacterial pneumonia and was censored for clinical follow-up. With a median follow-up of 22.5 months (range, 6-68 months), 9 of 16 evaluable patients (0.56) are alive disease-free, whereas 7 of 16 (0.44) relapsed with a median time to relapse of 9 months (range, 3-51 months). All patients treated with molecular disease achieved molecular CR. A significantly higher number of donor alloreactive NK cell clones was observed in responders over nonresponders. The infusion of higher number of alloreactive NK cells was associated with prolonged disease-free survival (0.81 vs. 0.14, respectively; P = 0.03). Conclusions: Infusion of purified NK cells is feasible in elderly AML patients as post-CR consolidation strategy. The clinical efficacy of adoptively transferred haploidentical NK cells may be improved by infusing high numbers of alloreactive NK cells.

Original languageEnglish
Pages (from-to)1914-1921
Number of pages8
JournalClinical Cancer Research
Volume22
Issue number8
DOIs
Publication statusPublished - Apr 15 2016

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Curti, A., Ruggeri, L., Parisi, S., Bontadini, A., Dan, E., Motta, M. R., Rizzi, S., Trabanelli, S., Ocadlikova, D., Lecciso, M., Giudice, V., Fruet, F., Urbani, E., Papayannidis, C., Martinelli, G., Bandini, G., Bonifazi, F., Lewis, R. E., Cavo, M., ... Lemoli, R. M. (2016). Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients. Clinical Cancer Research, 22(8), 1914-1921. https://doi.org/10.1158/1078-0432.CCR-15-1604