would be done to assess both the efficacy of the procedure and to test for 
possible side effects of the therapy as well as the follow-up frequencies are 
delineated in Appendix A. 
The minimal follow-up time to be confident of a full response of the 
patient's immune system is one year. In ADA-deficient patients who 
successfully receive an HLA-matched transplant, a PHA response is usually seen 
within 2-3 months. We expect an autologous gene therapy transplant to be no 
faster than a matched sibling transplant and it probably would be slower for 
several reasons. In a sibling transplant the patient is receiving T cells at 
various stages of maturation in the bone marrow infusion. Mature T cells can 
make up about 30% of the cells obtained from bone marrow harvest. Since these 
cells are already functional or soon to be functional they can be expected to 
need less time to provide immunological protection. The ultimate role that 
these T cells play in the final immunological reconstitution is not clear. In 
patients receiving a sibling BMT one cannot demonstrate cells of donor lineage 
In hematopoietic cells other than the lymphoid line(s). implying that the 
totipotential donor stem cell may not even persist. In the ADA-deficient 
patient the number of mature and maturing T cells will be much less, thus the 
role they could play in immunological reconstitution would necessarily be 
smaller (and slower). 
Another reason we would expect the immune reconstitution to be delayed 
with gene therapy as compared to a sibling BMT relates to the efficiency of 
gene transfer. With a sibling transplant all the cells transplanted will have 
functional ADA. whereas with gene therapy this will not be the case. If one 
assumes that only 1-10% of the transplanted cells will contain a functioning 
ADA gene, then a longer period of time would be required before a satisfactory 
number of ADA(+) cells would be produced in the patient to permit immune 
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Recombinant DNA Research, Volume 12 
