Recombinant DNA Advisory Committee - 
inclusion of the 14-year follow-up in the assent document and said that this would be 
revised and included. 
Dr. Post asked what the prognosis was for the children who would take part in the 
protocol and whether there was a likelihood that a significant percentage of them would 
completely recover. Dr. Brenner said the initial reason for the protocol was to improve 
the percentage of full recoveries from what is now 35-45%. There is some evidence that 
if bone marrow is purged, survival is prolonged. However, there is also evidence that a 
proportion of patients die from the effects of the purging and that it is important to find 
out if purging is removing leukemic cells or having possible immunological effects on the 
marrow. 
Mr. John Barton noted that, under the Federal Guidelines for Research With Children, a 
child cannot be asked to undergo a procedure with anything more than minimal risk 
unless the child is going to directly benefit from the procedure. He asked whether there 
was a way to confirm, either in animal models or in adults, whether this will benefit 
these children. Dr. Mclvor asked why the experiments were being done in children, 
rather than adults, since the disease also occurs in adults. 
Dr. Brenner asked Dr. Mirro, an associate at St. Jude's, to explain why the investigators 
believed it important to offer children the chance to benefit from this. Dr. Mirro said 
that this question was also brought up in the subcommittee discussion of the protocol 
and that the reasoning was that the procedure may be most beneficial in children 
because they are more likely to be able to tolerate an intensification of an ablative 
procedure, should the procedure show that it is residual leukemic populations in the 
patient's bone marrow that are responsible for the tumor regeneration. If it is found that 
the marrow is contaminated with leukemic cells and purging is required, children would 
have the greatest benefit of any transplant protocol since they are able to tolerate the 
ablative procedures. Children were really the ideal population for testing such a clinical 
approach. 
Mr. Mannix asked if children as a whole would benefit, or whether individual benefit is 
anticipated to be derived from the protocol. Dr. Mirro said that since children are most 
likely to undergo transplantation (allogeneic or autologous), they will benefit on the 
whole. However, the second part of the question dealing with individual benefit is 
critical and the hope of the investigators is to be able to modify transplant protocols 
based on knowledge gained as to the necessity for purging the bone marrow. Purging 
delays engraftment and exposes the children to possible opportunistic infection in the 
meantime. If purging is found necessary to prevent recurrence of the tumor, that this 
was a necessary risk, but that if it is found unnecessary, then it would save a great deal 
of risk to future transplant patients. 
Recombinant DNA Research, Volume 14 
[ 475 ] 
