Human Gene Therapy Subcommittee - 4/5/91 
relapse. Additionally, it would be a less sensitive test overall. Dr. Leventhal responded 
that if the in vitro predictions being made were relevant, there would be no need to use 
this system in vivo. 
An in-depth discussion took place as to whether a positive result could be achieved, 
based on the transduction efficiency and the labeling of non-cycling cells. Dr. Breimer 
pointed to the fact that neuroblastoma is a polyclonal event based on previous studies in 
acute lymphocytic leukemia (ALL); therefore, there would be no problem in detecting 
malignant cells in the marrow of these patients. Since there is no other methods 
currently available to assess different techniques of bone marrow purging, this 
experiment is necessary to be able to properly assess purging. 
Dr. Mclvor questioned whether it would be better to simply assay for neuroblastoma 
cells in the bone marrow itself, rather than using the marking experiment and reinfusing 
the marrow into the patient. Dr. Brenner said there were too few neuroblastoma cells 
present in the marrow of remission patients to assay. 
Dr. Kelley went through the list of questions formulated during the last review of the 
protocol in order to ensure that all were covered in the review, presentation, and 
discussion. Dr. Brenner pointed to both his written responses and his oral presentation 
for responses to all questions. 
Dr. Erickson pointed out that when the first tumor infiltrating lymphocyte (TIL) 
experiment was proposed, there was discussion that a marker for individual cells would 
be developed; he asked where current research stood relative to such a marker. Dr. 
Anderson said there had been a major effort underway to develop a single cell assay and 
that much had been learned; however, none has been successfully developed. 
Dr. Parkman said that even if the experiment were successful, the most that could be 
determined would be that relapse was caused by both exogenous and endogenous 
neuroblastoma cells. However, there would be no way to quantitate the participation of 
the exogenous versus endogenous cells in the ultimate outcome of relapse. Dr. Brenner 
said that if it could be determined that patients relapse because of malignant cells being 
reintroduced via the autologous bone marrow transplant, then he would be 
uncomfortable transplanting contaminated marrow. Regardless of quantitation, 
something would have to be done. 
Dr. Anderson noted that the discussions were becoming increasingly intricate and 
detailed and reminded the subcommittee that it was to be concerned with issues of risk- 
benefit, which he felt Dr. Brenner had proven to be acceptable. Dr. Parkman pointed to 
the previous discussions dealing with efficacy, safety, and feasibility. He noted that even 
if there is no risk involved, there needs to be proof given as to the probability of 
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