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.
Haematologica
; 92(1): 72-80, 2007 Jan.
Article
em En
| MEDLINE
| ID: mdl-17229638
ABSTRACT
BACKGROUND AND OBJECTIVES:
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. DESIGN ANDMETHODS:
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. INTERPRETATION ANDCONCLUSIONS:
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
/
Leucemia
/
Imunoterapia Adotiva
/
Transplante de Células-Tronco
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article