Recombinant DNA Advisory Committee - 2/10-11/92 
REGARDING A HUMAN GENE TRANSFER PROTOCOL ENTITLED: 
RETROVIRAL-MEDIA TED GENE TRANSFER OF BONE MARROW CELLS 
\ DURING AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR ACUTE 
LEUKEMIA 
Review— Dr. Doi 
Dr. Doi explained that the purpose of Dr. Cornetta's protocol is to determine if the 
transfer of leukemia cells during autologous BMT contributes to disease recurrence. This 
method is being considered since only 25 to 30% of patients with acute leukemia are able 
to undergo HLA sibling matched allogeneic BMT because of a lack of HLA-matched 
donors. Disease remission in the autologous BMT method could be due to three 
possibilities: (1) insufficient chemotherapy to eradicate the leukemia from the body; (2) 
the transfer of malignant cells present in the transplanted marrow; and (3) a combination 
of the first two reasons. The primary approach suggested by this protocol was to mark any 
leukemic cells present in the bone marrow preparation with the LNL6 retroviral vector 
which contains the gene coding for neomycin resistance prior to transplantation. At the 
time of patient relapse, the leukemic cells would be examined for evidence of the marker 
gene. If the marker is located, its presence would indicate that malignant cells were 
present in the transplanted marrow preparation and that these cells were partially the 
cause of the relapse. 
Several aspects of this protocol have been described in previous protocols submitted to the 
RAC. The experimental designs appear well planned, reasonable, and safe as far as the 
retroviral-mediated gene transfer is concerned. Careful patient selection is noted, as well 
as a thorough pretreatment evaluation. Also, the consequences of expression of the 
marker gene are considered; and its use is deemed to be safe, while the expression of the 
neomycin resistance gene does not exclude the use of other antibiotics. Several concerns 
were expressed by the HGTS regarding the technical feasibility and possible difficulties in 
interpretation of some aspects of the protocol. The concerns are: (1) the efficiency of 
transduction of leukemic cells; (2) the survival of cryopreserved transduced leukemic cells; 
(3) the limited examples of success in the transduction tests that have been conducted; and 
(4) whether the data concerning relapse of the disease could be clearly interpreted from 
the percentage of transduced leukemic cells that were transplanted and from the putative 
number of cells that live to relapse. The above concerns were addressed by Dr. Cometta 
in subsequent written data. Dr. Doi said that the HGTS had two concerns regarding the 
patient consent form, both of these issues were addressed by Dr. Cometta. 
Review— Dr. Brinckerhoff 
Dr. Brinckerhoff discussed the issue of the consent form. The investigators need to change 
Recombinant DNA Research, Volume 15 
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