June 1, 1990, Human Gene Therapy Subcommittee Minutes 
4. How will issues of long-term follow-up be communicated to the patients? What 
rules will there be for stopping the experiment? What facts about the protocol 
should definitely be disclosed to patients and families in the consent form? 
At this point, Dr. Walters adjourned the subcommittee for the luncheon recess and asked 
them to reassemble promptly at 1:30 p.m. 
Dr. Walters called the subcommittee to order for the afternoon session at 1:30 p.m. He 
decided to allow the investigators 30 minutes to reply to questions generated during the 
morning session. He noted there was one request for public comment which would be 
heard directly following the response of the investigators, after which the subcommittee 
would return to its discussion of the protocol. 
Dr. Blaese thanked the subcommittee members, the reviewers, and the consultants for 
their careful evaluation of the protocol. It clarified areas of the protocol which were 
ambiguous and that had not been spelled out clearly. 
Dr. Blaese distributed a handout listing inclusion and exclusion criteria. He said they 
intended to continue to use the criteria as listed in Section 3.0 of the protocol. They 
believe strongly that patients who are candidates for this therapy are those who had been 
on PEG-ADA and had opted against having a bone marrow transplant. He presented 
three case studies of patients who met current inclusion criteria and asked if there were 
any further questions on this issue. 
Dr. Leventhal asked if there was a specific ADA level that was considered as a criterion 
for inclusion/exclusion. Dr. Blaese said all the patients being considered had less than 2 
percent of normal levels of ADA but that no specific numbers have been set on a 
minimum/maximum ADA level for inclusion. 
Dr. Neiman asked if there was an attempt to use specific laboratory tests of immune 
function as predictors of a patient's prognosis. Dr. Blaese said that in vitro studies are so 
variable that it is difficult to establish what are appropriate tests. If the patients are 
unable to exhibit delayed type hypersensitivity skin tests to immunizing antigens, or if 
they are hypogammaglobulinemic or lymphopenic, then they are considered to be 
immune deficient. 
Dr. Blaese called on Dr. Anderson to reply to the question of "is it safe?" Dr. Anderson 
said the potential for oncogenesis, the possibility of a retrovirally mediated gene transfer 
producing cancer, is the clearly the question involved in the safety issue. He said the 
risk of this occurring was unknown, but there had been studies in mice and monkeys 
which have shown no indications of any oncogenesis. He said the risk is still there but 
that long-term follow-up of these animals is continuing. As time goes on, this question 
will be clearly answered. There will be a risk-benefit analysis, and it will include risk 
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