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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
- Source :
- Haematologica. 92:72-80
- Publication Year :
- 2007
- Publisher :
- Ferrata Storti Foundation (Haematologica), 2007.
-
Abstract
- 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.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.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.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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Adolescent
medicine.medical_treatment
Antigen-Presenting Cells
Immunotherapy, Adoptive
Donor lymphocyte infusion
Recurrence
Cell Line, Tumor
Internal medicine
medicine
Humans
Transplantation, Homologous
Cytotoxic T cell
Child
In Situ Hybridization, Fluorescence
Leukemia
Hematology
business.industry
Immunotherapy
Middle Aged
medicine.disease
Transplantation
CTL
Phenotype
Treatment Outcome
Immunology
Cancer research
Female
Stem cell
business
Stem Cell Transplantation
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15928721 and 03906078
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....ed71cc14711b07008f89a366cf1cdae0