Recombinant DMA Advisory Committee - 06/1-2/92 
Dr. Doi stated that Dr. Deisseroth responded to previous questions regarding the 
sensitivity of the assay and the variation observed in transduction efficiency among the 
various patient cells assayed. Dr. Doi inquired as to whether or not patients will be 
screened for transduction efficiency prior to acceptance into the protocol. 
Review-Dr. BrinckerhofT 
Dr. Brinckerhoff stated that this protocol is very well thought out, and that the 
investigators have extensive experience with the proposed procedures. Most of the 
concerns are whether or not Dr. Deisseroth can demonstrate double marking. There was 
very little data concerning GINa transduction versus LNL6. The investigators have 
provided very little comparison of transduction by these two vectors. 
Dr. Brinckerhoff noted that there will be a problem associated with interpretation of 
relapse in the presence of negative data. The only time that a positive result will be 
obtained is if relapse occurs as a result of a marked cell. There is always the possibility 
that a patient will relapse from a peripheral blood or marrow cell that is not marked. 
Dr. Brinckerhoff requested clarification regarding the PCR primers that will be used to 
detect the Philadelphia chromosome marker, BCR-abl mRNA. The investigators plan to 
determine the site of integration in order to distinguish clonality versus polyclonality. 
She asked Dr. Deisseroth if he will be using Southern blot analysis and restriction 
fragment length polymorphisms to determine this information. 
In conclusion, Dr. Brinckerhoff said that the investigators provided two informed consent 
documents, one was extremely clear and the other somewhat confusing. Both forms 
should be clear, concise, and similar in format. 
Other Comments 
Dr. Murray noted that one of the reviewers of this protocol, Ms. Nancy Buc, was not 
able to attend today's RAC meeting; therefore, no comments from Ms. Buc were 
presented. Dr. Parkman asked Dr. Deisseroth to address the availability of matched 
unrelated bone marrow transplant donors for these patients with CML. If patients are 
not cured by the use of autotransplantation and no long-term stabilization of their 
chronic phase disease is observed, than the proposed study may not be justified. 
Dr. Post suggested that it would be useful for Dr. Deisseroth to provide an update on his 
previously approved marking protocol. Dr. Post inquired as to whether the investigators 
performed experiments designed to look at the transduction of CD34( + ) enriched bone 
marrow cells. 
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Recombinant DNA Research, Volume 15 
