PMID- 11133743
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 97
IP  - 1
DP  - 2001 Jan 1
TI  - Administration of herpes simplex-thymidine kinase-expressing donor T cells with a 
      T-cell-depleted allogeneic marrow graft.
PG  - 63-72
AB  - 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.
FAU - Tiberghien, P
AU  - Tiberghien P
AD  - Etablissement Francais du Sang, Bourgogne/Franche-Comte, and Service d'Anatomie 
      Pathologique and Service d'Hematologie, Centre Hospitolier Universitoire (CHU) 
      Besancon, Besancon, France. pierre.tiberghien@univ-fcomte.fr
FAU - Ferrand, C
AU  - Ferrand C
FAU - Lioure, B
AU  - Lioure B
FAU - Milpied, N
AU  - Milpied N
FAU - Angonin, R
AU  - Angonin R
FAU - Deconinck, E
AU  - Deconinck E
FAU - Certoux, J M
AU  - Certoux JM
FAU - Robinet, E
AU  - Robinet E
FAU - Saas, P
AU  - Saas P
FAU - Petracca, B
AU  - Petracca B
FAU - Juttner, C
AU  - Juttner C
FAU - Reynolds, C W
AU  - Reynolds CW
FAU - Longo, D L
AU  - Longo DL
FAU - Herve, P
AU  - Herve P
FAU - Cahn, J Y
AU  - Cahn JY
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antiviral Agents)
RN  - 0 (CD3 Complex)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Adult
MH  - Antiviral Agents/administration & dosage/pharmacology
MH  - Bone Marrow Transplantation/immunology/*methods
MH  - CD3 Complex
MH  - Cell Culture Techniques
MH  - Disease-Free Survival
MH  - Epstein-Barr Virus Infections/complications
MH  - Female
MH  - Ganciclovir/administration & dosage/pharmacology
MH  - Graft Survival
MH  - Graft vs Host Disease/prevention & control/therapy
MH  - Herpes Simplex/drug therapy/enzymology
MH  - Humans
MH  - Lymphocyte Depletion/*methods
MH  - Lymphoproliferative Disorders/virology
MH  - Male
MH  - Middle Aged
MH  - Survival Rate
MH  - T-Lymphocytes/drug effects/*transplantation/virology
MH  - Thymidine Kinase/*administration & dosage/drug effects/genetics/therapeutic use
MH  - Time Factors
MH  - Transfection
MH  - Transplantation, Homologous/methods
MH  - Treatment Outcome
MH  - Viral Proteins/drug effects/genetics/therapeutic use
EDAT- 2001/01/03 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
AID - S0006-4971(20)48109-1 [pii]
AID - 10.1182/blood.v97.1.63 [doi]
PST - ppublish
SO  - Blood. 2001 Jan 1;97(1):63-72. doi: 10.1182/blood.v97.1.63.