Human Gene Therapy Subcommittee - 4/5/91 
AUTOLOGOUS BONE MARROW SUPPORT FOR TREATMENT OF 
RELAPSE/REFRACTORY NEUROBLASTOMA WITHOUT APPARENT BONE 
MARROW INVOLVEMENT: USE OF MARKER GENES TO INVESTIGATE THE 
BIOLOGY OF MARROW RECONSTITUTION AND THE MECHANISM OF RELAPSE: 
Dr. Erickson said the investigators had supplied additional data to show that the bone 
marrow cells from patients with neuroblastoma can be transduced with the LNL6 vector 
with an average efficiency of approximately Wo. The variability in transduction was 
quite high. Although the average was Wo, the median was actually much lower. 
Further, Dr. Erickson said the investigators were not able to present data indicating that 
the colonies were indeed neuroblastoma cells, but they promised to supply fluorescent 
antibody studies confirming that they are neuroblastoma cells. Given this variability in 
transduction ratios and the desirability of detecting bone marrow relapses due to small 
numbers of cells, it is questionable whether this protocol would provide the desired 
results. Further, he questioned whether the 33% fatality rate from treatment was 
acceptable. 
Dr. Walters called on Dr. Kelley for his comments. 
Dr. Kelley said he agreed with Dr. Erickson's review of the protocol. Dr. Kelley added 
that it might be helpful to have a written summary of responses to the questions posed at 
the last review of this protocol on July 30, 1990. 
Dr. Epstein said one major question discussed on July 30, 1990, concerned the 
demonstration that neuroblastoma cells could be transfected. The investigator supplied 
data in response to this, but he was unsure as to whether this data were adequate to 
prove the point. 
Dr. Parkman requested data concerning the percentages of cycling versus resting 
neuroblastoma cells in the patient, and the cloning efficiency of these cells obtained from 
the bone marrow. There is concern over the relevancy of presenting data on relapsed 
patients which may be a selected population due to chemotherapy selection. Data from 
these patients might produce a higher cloning efficiency relative to primary disease 
patients who have not relapsed or been treated with chemotherapy. 
Dr. Leventhal agreed that there are questions of cycling and non-cycling cells and their 
ability to cause relapse. There is also a concern about the investigators performing this 
experiment in patients without the knowledge of whether the relapse is monoclonal or 
polyclonal. If it is a safe experiment to perform, there are questions of where the 
experimental results would lead in determining a better therapy to employ for 
neuroblastoma patients. 
Recombinant DNA Research, Volume 14 
[567] 
