Recombinant DMA Advisory Committee - 
Mr. Mannix asked whether there was a chance that the children undergoing the protocol 
would benefit in subsequent treatment from the results of this experimental treatment as 
a result of assuming the risks involved. Dr. Mirro said that since most children will not 
undergo a second autologous transplant they will not benefit directly. Dr. Brenner added 
that some future protocols that are being planned would contain second autografts if the 
procedure is acceptable and therefore could result in benefit to these patients. 
Dr. Anderson explained that there are three categories of risk: 
1. Any additional risk because of the clinical procedure; 
2. The production of a recombinant virus that could be pathologic for the 
patient or for the health care professionals involved; and, 
3. Risk that the results of the random insertion may result in potential cancer 
production. 
He said since no additional clinical procedures were to be employed beyond what is 
already done in routine transplant, there is no additional risk from the first category. 
There has been considerable engineering of the vector and it has been shown not to 
present a major risk of producing pathologic retroviruses. However, a series of studies is 
being done to detect such an event should it take place. This leaves only the 
unanswered question of the risk of oncogenesis because of random insertion. In safety 
studies in monkeys, now approaching 70 monkey years in duration, there has been no 
evidence of a single tumor produced by a retrovirus. 
Dr. Walters added that during the HGTS discussion Dr. Mirro had addressed three 
points as to why children were included in the study. They were: 
1. There is less myeloid dysplasia in children than adults, therefore making 
them better candidates for the therapy; 
2. The terrible prognosis for children with AML; and, 
3. The fact that if purging is going to work, it is more likely to work in 
children than in adults. 
Dr. Walters said the subcommittee agreed that there were good reasons to do the study 
in children, although in general they thought they would prefer beginning with adults. 
When comparing the risks of the disease and the risks of standard therapy, the risks 
associated with cell marking are minimal. 
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Recombinant DNA Research, Volume 14 
