Recombinant DNA Advisory Committee - 06/1-2/92 
with GMCSF resulted in a 29% complete remission rate in advanced phase CML 
patients. Side effects have been observed as a result of this aggressive chemotherapy 
regimen, i.e., fluid retention, pleural effusions, pericarditis, and hypotension. For this 
reason, the investigators have chosen to reduce the cytarabine dose by 25% and use 
GCSF instead of GMCSF. Ten out of 54 patients were successfully converted to 
Philadelphia chromosome negative status. 
Dr. Stewart stated that all of these approaches justify the cytoreduction of CML patients 
prior to autologous bone marrow transplant in order to achieve Philadelphia 
chromosome negative metaphases. In vivo purging with gamma interferon has been a 
successful method of achieving Philadelphia chromosome negative metaphases in a small 
percentage of CML patients. 
Dr. Stewart presented data demonstrating that autologous bone marrow transplant is 
another modality that can induce Philadelphia chromosome negativity apart from pre- 
transplant chemotherapy, and that perhaps the addition of these two sequences is an 
appropriate approach to the treatment of CML. 
Dr. Geiduschek asked what the average life expectancy is for patients with chronic phase 
CML? Dr. Stewart answered that the average life expectancy is approximately 4-5 years. 
Other Comments 
Dr. Krogstad asked Dr. Dunbar to review the life expectancies for the patients 
undergoing these three studies? Dr. Dunbar replied that the life expectancy for 
myeloma with standard therapy is 24-36 months from diagnosis. Since the myeloma 
patients eligible for this protocol have already received standard chemotherapy, their life 
expectancy is less than 24 months. Breast cancer patients have an expected survival of 
12-18 months from presentation with metastatic breast cancer. The average life 
expectancy of patients with CML is 4-5 years; however, CML patients would not be 
eligible for this protocol unless they have been treated with interferon for at least one 
year and not responded. 
Mr. Capron asked Dr. Dunbar to expand on Dr. Geiduschek's question regarding the 
statistical upper limit of contamination that is detectible and how this relates to level of 
contamination observed in the rhesus monkey experiments. 
Dr. Dunbar stated that the upper limit of contamination is 15 particles per liter. The 
rhesus monkeys preparation contained between 10 4 and 10 6 helper virus particles per 
milliliter. There is a five log difference between the vector titer and helper virus titer. 
In regard to increasing the sensitivity of helper virus assays, Dr. Dunbar responded that 
this issue is generic for every vector; NIH 3T3 and HeLa cell amplifications and S+Lr 
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