title: Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients.
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.
authors.affiliation: Institute of Hematology, Department of Hematology and Oncological Sciences 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.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Addio
authors.forename: Andrea
authors.initials: A
authors.lastname: Bontadini
authors.forename: Elisa
authors.initials: E
authors.lastname: Dan
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Motta
authors.forename: Sara
authors.initials: S
authors.lastname: Trabanelli
authors.forename: Valeria
authors.initials: V
authors.lastname: Giudice
authors.forename: Elena
authors.initials: E
authors.lastname: Urbani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolini
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Fruet
authors.forename: Alessandro
authors.initials: A
authors.lastname: Isidori
authors.forename: Sarah
authors.initials: S
authors.lastname: Parisi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bandini
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D002469:Cell Separation; D003520:Cyclophosphamide / Q000008:administration & dosage; D005434:Flow Cytometry; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D007937:Leukapheresis; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000032:analysis*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D054340:Receptors, KIR; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine