NDLI: Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft.

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Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft.

Content Provider	Semantic Scholar
Author	Tiberghien, Pierre Ferrand, Christophe Lioure, Bruno Milpied, Nöel Angonin, Régis Deconinck, Erick Certoux, Jean Marie Robinet, Eric Saas, Philippe Petracca, Bruno Juttner, Clemens Reynolds, Craig W. Longo, Dan L. Hervé, Patrick Cahn, J. Y.
Copyright Year	2001
Abstract	Administration of donor T cells expressing the herpes simplex-thymidine kinase (HS-tk) with a hematopoietic stem cell (HSC) transplantation could allow, if graft-versus-host disease (GVHD) was to occur, a selective in vivo depletion of these T cells by the use of ganciclovir (GCV). The study evaluates the feasibility of such an approach. Escalating numbers of donor HS-tk-expressing CD3(+) gene-modified cells (GMCs) are infused with a T-cell-depleted bone marrow transplantation (BMT). Twelve patients with hematological malignancies received 2 x 10(5) (n = 5), 6 x 10(5) (n = 5), or 20 x 10(5) (n = 2) donor CD3(+) GMCs/kg with a BMT from a human leukocyte antigen (HLA)-identical sibling. No acute toxicity was associated with GMC administration. An early increase of circulating GMCs followed by a progressive decrease and long-lasting circulation of GMCs was documented. GCV treatment resulted in significant rapid decrease in circulating GMCs. Three patients developed acute GVHD, with a grade of at least II, while one patient developed chronic GVHD. Treatment with GCV alone was associated with a complete remission (CR) in 2 patients with acute GVHD, while the addition of glucocorticoids was necessary to achieve a CR in the last case. Long-lasting CR occurred with GCV treatment in the patient with chronic GVHD. Unfortunately, Epstein-Barr virus-lymphoproliferative disease occurred in 3 patients. Overall, the administration of low numbers of HS-tk-expressing T cells early following an HLA-identical BMT is associated with no acute toxicity, persistent circulation of the GMCs, and GCV-sensitive GVHD. Such findings open the way to the infusion of higher numbers of gene-modified donor T cells to enhance post-BMT immune competence while preserving GCV-sensitive alloreactivity.
Starting Page	63
Ending Page	72
Page Count	10
File Format	PDF HTM / HTML
DOI	10.1182/blood.V97.1.63
PubMed reference number	11133743
Journal	Medline
Volume Number	97
Issue Number	1
Alternate Webpage(s)	http://www.bloodjournal.org/content/bloodjournal/97/1/63.full.pdf?sso-checked=true
Alternate Webpage(s)	https://doi.org/10.1182/blood.V97.1.63
Journal	Blood
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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