e 
3.0 RATIONALE FOR CURRENT PROPOSAL 
The improvements made in autologous transplantation and the outcome for this 
procedure in patients in second complete remission suggests this may be a good 
treatment for children with AML. It permits dose escalation and the use of drugs 
such as busulfan which have excellent antileukemic properties but unpredictable and 
dose limiting marrow toxicity. Therefore, in this proposal we plan to continue to use 
ABMT for all children with AML (except those with an HLA-match sibling) in first 
complete remission. 
3.1 Autologous Marrow and Gene Marking 
Because the initial studies have shown that residual disease in the harvested 
marrow contributes to relapse, future autologous marrow transplants will add 
marrow purging to the treatment regimen. The combination of purging with 
gene marking allows the efficacy of the marrow cleansing step to be analyzed 
in vivo. Since two distinguishable markers, LNL6 and GIN are available for 
clinical use, it will be possible to compare the effectiveness of two separate 
purging techniques in the same individual. Two separate aliquots of marrow 
can be marked with either the GIN or LNL6 vectors and then exposed to one 
or other of the two purging techniques. The relative proportion of each 
marker in the blast cells at relapse will be dependent on the relative efficiency 
of each purging technique. 
3.2 Effects of Purging on Autologous Repopulation 
As we have shown that the marker gene will successfully be incorporated in 
long lived pluripotent cells in unpurged marrow, the current protocol will 
allow us to learn how such cells are affected by each purging technique. We 
will learn, for example, whether the sometimes profound delay in 
reconstitution following purging is a consequence of destruction of stem cells, 
and represents the time taken for residual host cells to recover from "ablative" 
therapy. We will also be able to compare, in the same individual, the relative 
effects of each purging technique on the pace and durability of reconstitution. 
3.3 Choice of Purging Techniques 
Despite many uncontrolled clinical trials, there is still no evidence that any 
purging technique is clinically effective. There are certainly no data to show 
that any one technique is superior to any other. To gain the maximum 
information in this initial study, we have chosen to compare a pharmacologic 
with an immunologic method of purging. Future studies may use other 
methods individually, or even in combination. 
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