title: Larger Size of Donor Alloreactive NK Cell Repertoire Correlates with Better Response to NK Cell Immunotherapy in Elderly Acute Myeloid Leukemia Patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy. antonio.curti2@unibo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Curti
authors.affiliation: Division of Hematology and Clinical Immunology, Department of Medicine, University of Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Parisi
authors.affiliation: Immunohematology Service and Blood Bank, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bontadini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dan
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Motta
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Rizzi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Trabanelli
authors.forename: Darina
authors.initials: D
authors.lastname: Ocadlikova
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Lecciso
authors.affiliation: Immunohematology Service and Blood Bank, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Giudice
authors.affiliation: Immunohematology Service and Blood Bank, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Fruet
authors.affiliation: Division of Hematology and Clinical Immunology, Department of Medicine, University of Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Urbani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bandini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonifazi
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Division of Hematology and Clinical Immunology, Department of Medicine, University of Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.affiliation: Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Azienda Ospedaliera Universitaria S. Martino-IST, Genoa, Italy.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
mesh_terms: D000367:Age Factors; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D007519:Isoantigens; D054341:Receptors, KIR3DL1