3. 
Clinical procedures. Including patient monitoring 
Describe the treatment that will be administered to patients and the 
diagnostic methods that will be used to monitor the success or 
failure of the treatment. If previous clinical studies using 
similar methods have been performed by yourself or others. Indicate 
their relevance to the proposed study. 
a. Hill cells (e.g.. bone marrow cells) be removed from patients 
and treated in vitro in preparation for gene therapy? If so. 
what kinds of cells will be removed from the patients, how 
many, how often, and at what intervals? 
Bone marrow cells will be removed from the iliac crests of the patient via 
multiple aspirations. This technique is the same as used for conventional bone 
marrow transplantation and will involve the use of appropriate anesthesia to 
minimize patient discomfort. The procedure will be performed under operating 
room conditions with protective isolation in order to minimize infectious risks 
to the patient. Approximately 10 to 15 ml per kg of patient body weight of 
marrow will be aspirated. Autologous or carefully screened (EBV and CMV 
negative) blood products will be available as needed. We anticipate the 
patient will need to be taken to the operating room only once. 
b. Will patients be treated to eliminate or reduce the number of 
cells containing malfunctioning genes (e.g.. through radiation 
or chemotherapy) prior to gene therapy? 
The initial trial with gene therapy would be designed so that no treatment 
would be used to eliminate or reduce the number of cells containing 
malfunctioning genes. Corrected cells should have a positive growth advantage 
and, therefore, the patient's own cells should not need to be destroyed. The 
patient would thus be exposed only to the minimal risks entailed by the 
multiple bone marrow aspirations and the reinfusion of the treated marrow cells 
and not to the additional risks entailed by treatments to reduce or eliminate 
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Recombinant DNA Research, Volume 12 
