Recombinant DNA Advisory Committee - 06/1-2/92 
Dr. D. Miller asked if these columns have been approved for use by the FDA? Dr. 
Dunbar responded that the columns have been approved for use in Phase I and Phase II 
clinical trials. Dr. Miller asked if the IND extended to this trial as well? Dr. Dunbar 
confirmed that these columns are approved for use in these protocols and stated that the 
current Phase I and Phase II trials have been very encouraging in terms of safety issues. 
Dr. Geiduschek asked Dr. Dunbar to address the rationalization of reconstituting 
patients with CD34( + ) selected cells in combination with unfractionated bone marrow 
cells and to explain the benefits that gene marking provide to the bone marrow 
transplantation protocol. Dr. Dunbar answered that the reason for CD34(+) selecting 
only 30% of the total bone marrow cell population is that they will not be using the back 
up marrow for additional therapeutic or experimental procedures. The remaining 70% 
of unfractionated marrow will be returned to the patient according to standard 
transplantation procedure. 
Presentation-Dr. Stewart 
Dr. Dunbar introduced her collaborator Dr. Stewart of the University of Virginia to 
provide background information regarding CML autologous transplants. Dr. Stewart 
described autologous bone marrow transplant studies in which CML patients were 
divided into two groups: chronic and second chronic phase versus accelerated or blast 
phase CML. First chronic phase patients received previous interferon therapy or were 
given interferon if their disease presented de novo. Interferon was administered to 
maximize the cytogenetic response. 
Patients who were in complete hematologic and cytogenetic remission had less than 5% 
Philadelphia chromosome positive cells. If these patients elected to have their bone 
marrow harvested, they would not be eligible to participate in the remainder of the 
protocol unless their disease progressed. Patients who were not in complete hematologic 
or cytogenetic remission are more at risk of relapse; therefore, this group of patients 
received aggressive cytoreductive therapy prior to bone marrow or peripheral blood 
harvesting, in an attempt to decrease the number of Philadelphia chromosome positive 
cells. 
Patients at high risk of relapse proceed immediately to cytoreductive therapy with 
cyclophosphamide and total body radiation followed by combined peripheral blood stem 
cell and autologous marrow transplant. Interferon was administered following cell 
transplant. 
This intensive therapy regimen resulted in transient Philadelphia chromosome negative 
cells in 53% of chronic and accelerated phase patients. Dr. Deisseroth's experiments 
have demonstrated that high dose cytosine arabinoside and daunorubicin in combination 
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