Recombinant DNA Advisory Committee - 06/1-2/92 
their disease. There are no allograft donors available for these patients. In addition, 
these patients have proven insensitive to interferon treatment, the only other alternative 
therapeutic approach. 
Dr. Deisseroth stated that chemotherapy will be administered to these patients in an 
attempt to induce a cytogenetic response. This response will allow for an opportunity to 
store normal progenitor cells from the patient for later use in autologous bone marrow 
transplantation. Progenitor cells are a more desirable choice over a total population of 
chronic phase cells for transplantation because data indicates that the probability of a 
durable cytogenetic response is greatly increased when normal diploid cells are used that 
are devoid of blasts. This increase in cytogenetic remission was observed when 
hematopoietic reconstitution with these diploid cells was preceded by systemic therapy. 
Dr. Deisseroth explained that the objective of the protocol is to assess the relative levels 
of contamination of the peripheral blood and bone marrow with blast cells and/or 
Philadelphia chromosome positive cells. The safety modified vectors which contain the 
gene coding for neomycin resistance, LNL6 and GINa, will be used to determine the 
origin of relapse. Does relapse occur as a result of systemic disease remaining after the 
systemic therapy; or from residual leukemic cells remaining in the fractionated marrow? 
Dr. Deisseroth stated that important data will be derived from the results of this study 
regarding the optimal source of hematopoietic tissue for reconstitution. This protocol is 
the first one designed to compare the relative capacity of peripheral blood versus bone 
marrow in reconstitution. 
Dr. Deisseroth explained that CML cells do not exhibit the surface cytoadhesion 
molecules that are present on normal myeloid cells. It is this molecule that allows cells 
to adhere to stromal elements within the marrow. It is hypothesized that there are large 
numbers of early abnormal progenitor cells below the level of clinical detection in the 
peripheral blood of these patients. 
Dr. Deisseroth presented data demonstrating the advantage of using purged, 
fractionated, hematopoietic cells for reconstitution. Patients who received fractionated 
bone marrow demonstrated increased survival over patients receiving unfractionated 
bone marrow. 
Dr. Deisseroth compared patients that received autologous bone marrow transplants to 
patients receiving allogeneic transplants. Early chronic phase patients who received 
autologous transplants responded similarly to those patients who received allogeneic 
transplants. These conclusions were based on data obtained from approximately 40 
patients receiving autologous transplants and 40 patients receiving allogeneic transplants. 
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Recombinant DNA Research, Volume 15 
