marrow aspirations may serve as portals of entry for infectious complications. 
The anesthesia itself holds the possibility for morbidity/mortality. By having 
the procedures done under controlled circumstances these risks would be 
minimized. As discussed in the safety section (I.B.2.c)» there is the 
possibility of viremia or malignancy resulting from the gene insertion 
procedure itself or its aftermath. 
The patient may receive only a partial response to the therapy. This 
partial response could produce "windows" or holes in the patient's immune 
system that may result in morbidity/mortality. 
The partial response may manifest itself as an imbalanced immune system. 
The normal checks and balances of the immune system may be perturbed so that 
the patient is at risk for autoimmune pheomenon. These autoimmune disorders 
may or may not be responsive to conventional therapy. If this problem becomes 
sufficiently severe the patient may need to undergo a repeated round of gene 
therapy or perhaps even undergo alternative therapy (such as BMT) to try to 
alleviate the dysfunction. 
The patient may experience only a transient response to gene therapy. An 
inital rise in immune function may wane for a variety of reasons. If this were 
to occur the patient may require periodic repeat gene therapy or may require 
alternative therapy. A partial response has been helpful in reducing the 
morbidity associated with untreated ADA deficiency, but the longer the 
patient's immune system is abnormal, the higher the probability of irreversible 
effects on the patient because of the immune defects. 
We feel that the use of retroviral -mediated gene transfer, under optimal 
conditions, would not subject the patient to any serious short-term risks. 
However, as discussed in the safety section (I.B.2.C.). there are a number of 
concerns with respect to potentially serious long-term consequences. 
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Recombinant DNA Research, Volume 12 
