Recombinant DMA Advisory Committee - 
rapidly in tissue culture. No change was noted in the patient's absolute T cell count for 
the first 20 days or so, but then her T cell count began to rise, until by the third infusion, 
it had increased dramatically. After the third infusion there was some difficulty with 
tissue culture contamination, and the fourth treatment was postponed until this problem 
was solved. During this 50 day period between the third and fourth infusions, the 
patient's lymphocyte count reverted to pre-therapy levels and rose again after the fourth 
infusion. 
Dr. Blaese said that the polymerase chain reaction (PCR) was used to determine how 
many of the peripheral T cells contained the ADA gene. Nothing was seen until prior to 
the second infusion when there was an increase in cell count and detectable numbers of 
gene-containing cells appeared in the peripheral blood. However, following the second 
infusion they disappeared and then reappeared. One hour after the third infusion the 
cells produced a very strong PCR signal, this has remained at a relatively high level, and 
seems to persist as long as 40 days. 
He said that the peripheral T lymphocytes were surviving for at least twice as long as the 
cells in the previous N2/TIL protocol, but that there were no data available to confirm 
how long they will survive. TTie number of cells that the patients had received in this 
protocol is only one-tenth the number that were infused in the N2/TIL protocol. 
Therefore, it is obvious that there are differences in the characteristics of a tissue 
lymphocyte such as the TILs and the circulating peripheral T cells that are being used in 
this protocol. 
Dr. Blaese presented data showing evidence of immune reconstitution in the patients as 
measured by antibody responses to isohemagglutinin which was the strongest evidence 
that the therapy was having an effect on the patient's immune system. 
Dr. Mclvor asked for clarification on the quantitation of the PCR results relating to the 
actual numbers of cells in the blood stream that actually contain the ADA gene. Dr. 
Blaese said he could not quantify it at this point because the scales being used for the 
PCR analysis were not adequate. The investigators were eager to determine those 
numbers. Cells are being banked so that after the first phase of the protocol is 
complete, they can be run as a group and quantified. 
Dr. Krogstad asked what type of T lymphocytes were surviving in culture and in the 
patient. Dr. Blaese said that the first patient had a predominance of CDS cells in 
peripheral blood at the start of therapy and that with each cycle of growth in culture 
there has been a progressive increase in CDS numbers over time. 
Dr. Atlas asked whether there was any opinion on the part of the investigators as to why 
there was seemingly a lag period between the first and second infusions and then the 
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