Human Gene Therapy Subcommittee - 11/30/90 
Dr. Mclvor asked if this would require an absolute model of AML in order to 
perform these assessments. He suggested using the brown Norway rat as a 
transplantable model of human AML. Dr. Ihle said he had not worked with this 
model previously. Dr. Parkman noted that in this model, all the cells were 
constantly cycling. Dr. Ihle said that in this case, the study would bias the results 
because of the lack of a non-cycling cell population. There is no good animal model 
at this time. 
Dr. Epstein cautioned that no animal model was required for the protocol which was 
discussed earlier in the day. This protocol should not be held to a higher standard 
than the previous protocol. The investigators have met the requirements of the 
HGTS, have identified the questions involved, and have offered some clever ways to 
possibly get the answers to these questions. Dr. Epstein moved for approval of the 
protocol. Dr. Mclvor seconded the motion. 
Dr. Parkman asked if a patient would be excluded from the protocol if his/her cells 
were untransfectible or transfectible only at a low level due to the heterogeneity of 
their AML. The possibility of a low transduction rate has not been addressed in the 
protocol. Dr. Brenner said this possibility was not mentioned because it may not 
occur. The clonigenic cells in methylcellulose are assumed to be representative of 
the cells in vivo. Therefore, a low infectivity rate is not an inclusion or exclusion 
criterion. 
Dr. Epstein asked if a group of patients with a very low frequency of initial 
transduction would ultimately be limited or denied access to the trial in order not to 
skew the results. 
Dr. Kelley asked the investigators if there was any real advantage to studying 
children rather than adults. Dr. Mirro responded that there were subtle differences 
between AML in adults and children. In children, there is less myelodysplasia. The 
protocol will provide information that is not totally unique to children; it will provide 
overlap into the adult population with AML. Further, children with AML have a 
long term survival rate of about 40%. Deaths from AML account for almost half 
the deaths from leukemia in childhood despite the fact that AML only accounts for 
25% of all childhood leukemias. 
Dr. Mirro noted that purging is a real risk to children, often resulting in failure to 
engraft. If data demonstrates that purging is not really necessary, then ablative 
preparation could be manipulated and/or increased with hopes of improving results 
of BMT. 
Recombinant DNA Research, Volume 14 
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