TY - JOUR
T1 - Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients
AU - Curti, Antonio
AU - Ruggeri, Loredana
AU - Parisi, Sarah
AU - Bontadini, Andrea
AU - Dan, Elisa
AU - Motta, Maria Rosa
AU - Rizzi, Simonetta
AU - Trabanelli, Sara
AU - Ocadlikova, Darina
AU - Lecciso, Mariangela
AU - Giudice, Valeria
AU - Fruet, Fiorenza
AU - Urbani, Elena
AU - Papayannidis, Cristina
AU - Martinelli, Giovanni
AU - Bandini, Giuseppe
AU - Bonifazi, Francesca
AU - Lewis, Russell E.
AU - Cavo, Michele
AU - Velardi, Andrea
AU - Lemoli, Roberto M.
PY - 2016/4/15
Y1 - 2016/4/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-15-1604
DO - 10.1158/1078-0432.CCR-15-1604
M3 - Article
AN - SCOPUS:84966769819
VL - 22
SP - 1914
EP - 1921
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 8
ER -