Bone marrow or blood stem cell transplantation is used to treat a wide range of life-threatening conditions. T lymphocytes carried in the graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause graft-versus-host disease (GVHD). To safeguard against GVHD, the investigators propose modifying T cells to encode a 'switch' so that they can be eliminated if problems arise. Children receiving half-matched (haploidentical) transplants from a parent are most likely to benefit from this strategy. At present these patients receive blood stem cells from a parent, but the T cells are removed because the risk of serious GVHD is unacceptable. This means that they are much more likely to suffer from life threatening infections or experience a relapse of leukaemia. The investigators want to use gene therapy to produce "safe" T cells which can be used to strengthen the transplant and prevent these serious complications.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD * dose 1 5x104 cells/kg * dose 2 5x105 cells/kg
Great Ormond Street Hospital for Children NHS Trust
London, United Kingdom
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells
Time frame: 12 months after final dose
Incidence of GvHD
Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells
Time frame: 12 months after final dose
Patient survival
Patient survial is measured until 12 months after administration of the final dose of gene modified cells
Time frame: 12 months after final dose
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