Human Gene Therapy Subcommittee - 11/30/90 
Dr. Walters called on Dr. Mclvor to begin the discussion on the next protocol. Dr. 
Mclvor said that a lot of the issues in this protocol had been introduced in the first 
protocol reviewed at this meeting, and that written copies of his review have been 
distributed. Therefore, he said that he would briefly cover the major points of the 
protocol. 
Dr. Mclvor said that the objectives of the study are laudable because leukemia is a 
serious disease. There is a need for improved therapy, a need for understanding of 
the biology of leukemia, and a need for a clear understanding of relapse after 
marrow transplant. The task before the HGTS is to determine whether the 
proposed procedure would be able to provide information that would result in 
improved therapy by autologous bone marrow transplantation. 
Dr. Mclvor said that safety is an issue. Again, this protocol does not differ from the 
first one reviewed at this meeting in that the genes were being transferred via 
retroviral vectors into marrow, and marrow cells have a potential for long life. 
Therefore, this increased persistence of the inserted genes creates a finite risk; in 
cases where the genes are transferred into lymphocytes, there is more of a risk. 
The efficiency of retroviral-mediated gene transfer into human bone marrow cells is 
an issue. The exact numbers of marrow cells to be transduced was not discussed in 
the protocol. The investigators need to address what is the number of these cells, 
what is the amount of virus that is going to be used, whether there is a sufficient 
ratio of virus to cells to effect tagging, and what procedures are planned to 
determine whether effective gene transfer has occurred in those populations before 
reintroduction into the patient. 
There were some preliminary data on gene transfer into acute myelogenous 
leukemia (AML) blast cells, and this data needs to be reviewed during the 
discussion. 
Dr. Mclvor said that details were lacking on how a determination would be made as 
to whether the regenerated tumor came from donor cells or from host cells. 
Restriction fragment length polymorphism (RFLP) analysis and Southern blot 
analysis would be employed if relapse was observed, but the specific techniques for 
these analyses were lacking in the protocol. The investigators need to provide 
preclinical data showing that these techniques are capable of determining the source 
of the regenerated leukemia. 
Dr. Mclvor said that another issue is that the experiment would be conducted in 
children. Since the disease afflicts both adults and children, the experiment should 
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