Phase I/II feasibility study evaluating the generation of leukemia-reactive cytotoxic T lymphocyte lines for treatment of patients with relapsed leukemia after allogeneic stem cell transplantation.
OBJECTIVE
Graft-versus-host-disease may be avoided and the likelihood of a graft-versus-leukemia reaction increased by infusion of in vitro generated, leukemia-reactive, cytotoxic T lymphocyte (CTL) lines as treatment for patients with relapsed leukemia after allogeneic stem cell transplantation, instead of donor lymphocyte infusion. The aim of this study phase I/II study was to assess the feasibility of large-scale in vitro generation of leukemia-reactive CTL for clinical use.


METHODS
Using a modified limiting dilution culture system donor T cells were stimulated with HLA-identical leukemic antigen presenting cells. Feasibility experiments demonstrated that in 16 of 27 donor-recipient pairs tested a CTL line could be generated. Twelve of these 16 patients developed a relapse and for 11 of these 12 patients a CTL line was generated under Good Manufacturing Practice conditions.


RESULTS
The CTL lines showed moderate to high cytotoxic activity against original recipient leukemic cells in vitro. Eight patients with a relapse received from one to seven CTL lines. One patient entered a complete remission after CTL infusion only, one entered a complete remission after combined CTL infusion and donor lymphocyte infusion, two patients had temporarily stable disease, and in four patients no response was observed.


CONCLUSIONS
Although the current procedure to generate these CTL lines is feasible, the strategy is logistically complex and time-consuming, and needs further improvement. Key words: cellular immunotherapy, CTL, leukemia, allogeneic stem cell transplantation.
Marijt
Erik
E
Department of Hematology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. wafmarijt.hematology@lumc.nl
Wafelman
Amon
A
van der Hoorn
Menno
M
van Bergen
Cornelis
C
Bongaerts
Rian
R
van Luxemburg-Heijs
Simone
S
van den Muijsenberg
Joost
J
Wolbers
Judith Olde
JO
van der Werff
Nicole
N
Willemze
Roel
R
Falkenburg
Frederik
F
D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome