Human Gene Therapy Subcommittee - 11/30/90 
if the patients were clearly informed of the risks/benefits and were able to 
understand the financial obligations involved, adults should be capable of giving 
informed consent. 
Dr. Mahoney added that there appeared to be little risk associated with such an 
experiment, and that the key was whether there was a reasonable expectation that 
any scientific information would come from the experiments. This risk should be 
clarified, and then it would be easier to judge whether the risks and burdens to the 
patient were justified. 
Dr. Cometta thanked the reviewers and HGTS members for the time they spent 
considering his protocol. He said he would clarify the goals of the protocol. The 
magnitude of the risk involved with the protocol was unknown, therefore, it is 
difficult to ascertain whether such risk is acceptable. The risk should be viewed 
from two perspectives: (1) the patient whose participation must be viewed as 
altruistic because of the lack of direct therapeutic benefit; and (2) withholding the 
potential information gained from such a study would increase the risk to patients 
who are in second remission and eligible for autologous bone marrow transplant 
(BMT). 
Dr. Cometta noted that the patients are already assuming risks because it is known 
that treatment-related mortality is estimated at 10% with autologous BMT. Seventy 
to 80% of patients undergoing BMT will not benefit. The current approach has 
been for the patient to undergo chemotherapy or monoclonal antibody treatment to 
purge the bone marrow. These procedures pose risks of infection or fatal 
hemorrhage due to toxic effects or delays in engraftment. 
Dr. Cometta said the goal of the protocol is to try to determine if leukemic cells at 
relapse have arisen from the transplanted marrow. This result will indicate the 
necessity to purge bone marrow during autologous bone marrow transplant (BMT). 
The main disadvantage to the protocol is that fewer than 100% of the cells being 
transplanted are marked; however, it is advantageous in the sense that this particular 
procedure has never been used in autologous BMT. There is a possibility that a 
100% labeling with a retroviral vector may delay engraftment, therefore, increase the 
risk to the patient. The goal was to maximize the scientific aspects of the protocol 
rather than to minimize the risk of manipulations to the patient while providing a 
significant chance of providing answers addressed in the protocol. 
The critical factor in the success of the protocol is the tumor burden in the 
transplanted marrow, specifically, the number of transplanted cells capable of 
causing relapse. Based on studies published in the New England Journal of Medicine 
Recombinant DNA Research, Volume 14 
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