title: Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study.
abstract: OBJECTIVE
  Cytokine-induced killer (CIK) cells have shown anti-leukemic activity and little graft-versus-host disease (GVHD) in several animal models. The safety of these cells in autologous settings has been shown. We performed a phase I study of allogeneic (donor's) CIK cells in patients relapsing after allogeneic haematopoietic stem cell transplantation (HSCT).
  
  
  METHODS
  Eleven patients with acute myelogenous leukemia (n=4), Hodgkin's disease (n=3), chronic myelomonocytic leukemia, (n=1), pre-B acute lymphoblastic leukemia (n=1) and myelodysplasia (n=2), all of whom had relapsed after sibling (n=6) or matched unrelated donor (n=5) HSCT, entered this study.
  
  
  RESULTS
  Before CIK administration, six patients had received other salvage treatments including chemotherapy (n=5), radiotherapy (n=1) and unmanipulated donor lymphocytes (n=6) without any significant tumor response. The median number of CIK infusions was two (range 1-7) and the median number of total CIK cells was 12.4x106/kg (range 7.2-87.4). The infusions were well tolerated and no acute or late infusion-related reactions were recorded. Acute GVHD (grade I and II) was observed in four patients, 30 days after the last CIK infusion, and progressed into extensive chronic GVHD in two cases. Disease progression and death occurred in six patients. One patient had stable disease, one had hematologic improvement and three achieved complete responses.
  
  
  CONCLUSIONS
  This study shows that the production of allogeneic CIK cells is feasible under clinical-grade conditions, well tolerated and may contribute to clinical responses.
authors.affiliation: Laboratory of Cellular and Gene Therapy G. Lanzani, Ospedali Riuniti di Bergamo, Bergamo, Italy. mintrona@ospedaliriuniti.bergamo.it
authors.forename: Martino
authors.initials: M
authors.lastname: Introna
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Borleri
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
authors.forename: Marta
authors.initials: M
authors.lastname: Franceschetti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Barbui
authors.forename: Raewyn
authors.initials: R
authors.lastname: Broady
authors.forename: Erica
authors.initials: E
authors.lastname: Dander
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gaipa
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Amico
authors.forename: Ettore
authors.initials: E
authors.lastname: Biagi
authors.forename: Matteo
authors.initials: M
authors.lastname: Parma
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Pogliani
authors.forename: Orietta
authors.initials: O
authors.lastname: Spinelli
authors.forename: Donatella
authors.initials: D
authors.lastname: Baronciani
authors.forename: Anna
authors.initials: A
authors.lastname: Grassi
authors.forename: Josée
authors.initials: J
authors.lastname: Golay
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000328:Adult; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000637:transplantation*; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines