Recombinant DNA Advisory Committee - 2/10-11/92 
not gene corrected. The infusion induced a very prompt increase in the peripheral 
circulating lymphocyte count. Within three months of beginning the protocol, the 
lymphocyte count had returned to normal. There was a period of three months during 
which the patient was not treated because of technical problems with culture 
contamination. During this period, there was a discouraging fall in the peripheral 
lymphocyte count. After the treatment began again, the T lymphocyte count returned to 
the normal range. 
The patient stopped treatment in July 1991. Six months following treatment, her 
lymphocyte count remained stable. She had positive skin tests to diphtheria, Candida, and 
tetanus toxoid. Cytotoxicity assays demonstrated that she had acquired cytolytic T 
lymphocyte function. The ADA levels were measured in the patient's peripheral 
mononuclear cells during the treatment period. Prior to treatment, ADA was essentially 
undetectable. During treatment, there was an increase in the ADA level. After the 
infusions stopped in July 1991, the ADA levels remained relatively stable. Even when the 
lymphocyte count fell during the three months when the patient could not be treated, the 
ADA level was maintained. 
In response to a question from Dr. Krogstad, Dr. Blaese said that quantitative analysis of 
gene corrected cells at each time point had not been completed, but data indicated that 
corrected cells had the predicted survival advantage over non-corrected cells. 
Dr. Blaese stated that the first patient, who was previously confined at home and isolated 
from the public, is now attending public school. A second patient was enrolled in the 
protocol in January 1991. She also exhibited an improvement in lymphocyte count, has a 
normal isoagglutinin response, and has acquired cytolytic T lymphocyte function. 
Dr. Blaese explained that this amendment to the ADA protocol proposes to insert the 
gene for ADA into peripheral blood stem cells. The rationale behind this proposal is that 
even with the positive response that has been observed with the current treatment, there 
are still deficiencies in the T lymphocyte repertoire. Since it is unclear if the improved 
immune response will last, there would be an advantage to inserting the ADA gene into 
the stem cells in order to achieve these levels permanently. 
Dr. Leventhal asked Dr. Blaese how long immune responses had been detected in patients 
receiving BMT with stem cells and have any grafts been rejected. Dr. Blaese said that he 
only knew of one identical BMT rejection. Permanent reconstitution should be expected 
with matched sibling donors. 
Following the status report on the original protocol, Dr. B. Murray introduced the 
proposed amendment to Appendix D-XV of the NIH Guidelines. 
Recombinant DNA Research, Volume 15 
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