structure of these human and murine viral 
sequences, such as tRNA binding sites, 
make the likelihood of successful 
recombination extremely small. 
Recombination between MLV and human 
endogenous retroviral sequences has not 
been reported in primate cells in vivo . 
This question was specifically addressed 
in the LNL-6 TIL human gene transfer 
clinical trial. After retroviral 
insertion, reverse transcriptase (RT) 
assays have never detected RT activity. 
7.44) Introduction of the neo R gene 
The neo R gene product, neomycin 
phosphotransferase, phosphorylates the 
3' -hydroxyl group of the aminohexose I of 
neomycin and its analogues, thereby 
inactivating the antibiotic. While 
amikacin may be inactivated by this 
enzyme, gentamicin and tobramycin do not 
contain a hydroxyl at the 3 ' position and 
are not inactivated. Therefore, 
introduction of the neo R gene would not 
exclude the use of aminoglycosides or any 
other conventional antibiotic that may be 
needed in the clinical management of 
these patients. 
8.0 STATISTICS 
8.1) Theoretical Considerations 
Since all the patients in our study are destined to 
relapse if they are not transplanted, we know that some 
residual leukemic cells are harbored in their marrow. At 
present we do not know if leukemic cells in the 
transplanted marrow contribute to relapse. The likelihood 
of success in our gene marking study will be based on the 
percentage of transduced leukemic cells transplanted and 
the number of those cells that lead to relapse. 
Based on the best available data regarding tumor 
reduction with chemotherapy, the estimate of transplanted 
leukemic cells is at least 100 (based on two 4-fold 
reduction in tumor burden after induction and 
consolidation chemotherapy with an estimated 10 11 
leukemia cells at relapse and harvesting approximately 
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