Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study.
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.
Introna
Martino
M
Laboratory of Cellular and Gene Therapy G. Lanzani, Ospedali Riuniti di Bergamo, Bergamo, Italy. mintrona@ospedaliriuniti.bergamo.it
Borleri
Gianmaria
G
Conti
Elena
E
Franceschetti
Marta
M
Barbui
Anna Maria
AM
Broady
Raewyn
R
Dander
Erica
E
Gaipa
Giuseppe
G
D'Amico
Giovanna
G
Biagi
Ettore
E
Parma
Matteo
M
Pogliani
Enrico M
EM
Spinelli
Orietta
O
Baronciani
Donatella
D
Grassi
Anna
A
Golay
Josée
J
Barbui
Tiziano
T
Biondi
Andrea
A
Rambaldi
Alessandro
A
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
D016207:Cytokines