Human Gene Therapy Subcommittee - 11/30/90 
by Yamada, patients with acute lymphocytic leukemia (ALL) who had a B cell gene 
rearrangement were detectable by PCR. It was found that in patients who had been 
treated with standard chemotherapy and were in complete remission for 18 months, 
between .004-2.0% of the marrow cells appeared to be of leukemic origin by PCR 
analysis. With further maintenance chemotherapy, all of the patients went on to 
have no detectable leukemic clones in their marrow and appeared to be cured by 
chemotherapy. Further, proof of high tumor burden comes from clinical studies 
which show that patients relapse in as short a period as 1-2 months after 
transplantation. 
Dr. Cometta said he wished to clarify some specific points in his October 23, 1990, 
letter. The first point to be clarified surrounds the analysis of the cells in relapse 
located on the final page of the letter. The protocol may be misleading as to the 
approach being used. Previous data indicated that in autologous BMT in primates, 
the later progenitor cells BFU-E, CFU-E, and CFU-GM were transduced with the 
LNL6 vector, but the pluripotent stem cells did not appear to be transduced. The 
low transduction efficiency of stem cells is why a simple gene transfer protocol is 
being used, rather than considering gene therapy protocols in autologous BMT. 
Colony-forming assays in normal marrow would provide information about the time 
course of gene expression and the presence of genes after autologous BMT. These 
assays will provide information that will be used to gauge the background signal 
produced by the vector that may be present in future PCR analyses after relapse. 
Dr. Cometta said that most of the assessments will be based on PCR values, and 
that positive PCRs would lead to additional screening by Southern blot analysis and 
FACS sorting to look at individual cell populations over time. It is important to 
have the opportunity to perform these assessments over time to help differentiate 
the signals that may be obtained from normal marrow from those obtained from 
leukemic cells. 
Dr. Cometta addressed concerns about the informed consent document. Attempts 
have been made to clearly and concisely inform the patient of the risks involved with 
the protocol. This type of document should always be discussed with the patient by 
the physician offering the protocol, and a high priority was being placed on the 
responsibility of the physician adequately to counsel the patient as to the risks of the 
procedure. 
Dr. Cometta responded to questions regarding third party payers. The wording of 
the clause dealing with unexpected events caused by the therapy was a standard 
clause supplied by the University of Wisconsin, and it was contained in even the 
most basic protocols. The clause did not say the patients were ineligible for 
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Recombinant DNA Research, Volume 14 
