Recombinant DNA Advisory Committee - 06/1-2/92 
In response to Mr. Barton and Dr. Dronamraju's concerns regarding the ability to detect 
a marked stem cell after transplantation, Dr. Dunbar responded that the rhesus monkey 
data indicates that if 0.3% of the transplanted stem cells are contributing to relapse, 
marked cells would be detectable by PCR. Based on pre-clinical data, the investigators 
estimate that 100 transduced cells will be administered to the patient. This number is 
approximately one-third of the total stem cells given back in the bone marrow or 
peripheral blood transplants. If hematopoiesis is polyclonal after bone marrow 
transplant and if 1% of these returned cells are contributing to hematopoiesis at any 
given time, than this level should be detectable by PCR. The patients will be followed 
over prolonged periods, and they will be monitored for evidence of cycling or changes 
that are contributing to hematopoiesis. 
Dr. Dronamraju asked if there were any data corresponding to this response in the 
primate setting. Dr. Dunbar answered that there are monkeys that have received cells 
transduced with clinical grade vectors that have between 1 and 10% PCR positive 
mononuclear cells. These animals are not far enough out to be certain that stem cell 
gene transfer has occurred. Expression must be stable for between six months and one 
year in the primate model to ensure stem cell transfer. 
Dr. Dunbar addressed the issue of life expectancy. The median survival for patients with 
myeloma is between 24 and 36 months. Since these patients have already received 
standard therapy, their disease is at an aggressive stage. Without further treatment, the 
life expectancy of these patients is between 6 and 18 months. The average life 
expectancy for patients with CML and breast cancer is also approximately 18 months. 
In response to Dr. Dronamraju's request for increased reporting, Dr. Dunbar said she 
would comply with the reporting schedule determined by the RAC; however, the RAC 
only requires annual reporting. Maybe the reporting requirements should be decided 
internally. 
Dr. Dunbar stated that she would revise the informed consent document to include 
simplified language; however, it would be preferable to have only one document versus 
two. 
Dr. Dunbar discussed future plans based on the outcome of these protocols. The 
purging regimen is an open question. The information that will be obtained regarding 
hematopoietic stem cell marking will be extremely important in the design of future 
protocols for CML, myeloma, and breast cancer as well as diseases involving genetic 
defects of hematopoietic stem cells such as sickle cell anemia, hemoglobinopathies, and 
Gaucher's disease. 
In conclusion, Dr. Dunbar stated that there is really nothing remarkable about the 
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Recombinant DNA Research, Volume 15 
