Recombinant DNA Advisoiy Committee - 2/10-11/92 
involves administering a CD34 selected, gene-altered fraction to see whether the cells 
differentiate and are in the peripheral blood. If this protocol is successful, the 
investigators will begin to determine efficacy by stopping the T lymphocyte infusions and 
looking for improvement or maintenance. Given the degree of illness in these children 
and knowing that T lymphocyte infusions are beneficial, the investigators will minimize the 
risks by continuing the infusions. 
Dr. Post stated that he would not approve this amended protocol if it were the only 
therapy being provided; however, since this new cell population will be administered in 
conjunction with the original therapy, there is a strong likelihood that the investigators will 
be able to learn a great deal from these experiments. He said that he was in favor of the 
amendment. 
Dr. R. Murray asked whether CD34( + ) cells might express ADA in vitro and not in vivo. 
Dr. Culver stated that there is no way to determine if the gene will be expressed in vitro in 
the lymphoid lineage, and the only in vivo model is the ADA-deficient child. 
Dr. Mclvor said that it would be possible to transduce CD34(+) cells from an ADA- 
deficient patient and then culture those cells until they differentiate into myeloid cells. 
This cell population is a different lineage; however, it would be possible to test for ADA 
expression in these second generation cells. This type of in vitro expression study could be 
conducted to determine whether the vector is successful. 
Dr. Kelley asked if these experiments could be performed using the nude mouse as a 
model. Dr. Culver responded negatively. Nude mice have no thymus; therefore, 
differentiation of lymphoid cells could not be examined. There is no reason to believe 
that the myeloid lineages have any correlation to the lymphoid lineages. Dr. B. Murray 
asked about the differentiation capabilities of CD34( + ) cells. Dr. Dunbar said that in in 
vitro experiments, the cells form all the different types of myeloid lineage colonies, and 
there are data from SCID mice indicating that cells differentiate into T lymphocytes. 
With no further questions or comments, Dr. B. Murray called for a vote on the 
amendment to the ADA protocol. The motion to approve the amended protocol passed 
by a vote of 11 in favor, 3 opposed, and 2 abstentions. There was further discussion 
concerning the patient consent form. Dr. R. Murray stated that he voted in favor of the 
protocol even though the amended protocol does not have a therapeutic benefit; however, 
important information could be gained from the amended protocol. The consent form 
should reflect the probability that the addition to the protocol may not be of therapeutic 
benefit. 
XII. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES 
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