Recombinant DNA Advisory Committee - 06/1-2/92 
clinical aspects of any of these three protocols. For all of these diseases, autologous 
bone marrow transplantation is state-of-the-art aggressive treatment. These patients 
have incurable disease and are not eligible to receive an allogeneic transplant. Patients 
eligible for treatment at the NIH will be treated at no cost. 
Dr. D. Miller asked Dr. Dunbar to discuss the protocol outlines for the three different 
diseases as detailed in Appendix A of the protocol. Dr. Dunbar explained that there are 
three protocols: breast cancer, CML, and multiple myeloma. All of the patients have 
proven chemotherapy responsive. The multiple myeloma and CML protocols involve 
both bone marrow and peripheral blood, whereas, the breast cancer protocol involves 
only bone marrow. In the multiple myeloma protocol, patients will receive an 
intermediate dose of Cytoxan and will receive the hematopoietic growth factor, GCSF. 
When the patient's white count reaches 1,000, peripheral blood stem cell apheresis will 
be performed. 
In the CML protocol, patients will be treated with very high doses of cytosine 
arabinoside and daunorubicin to induce a competitive advantage for normal, non-BCR- 
abl bearing non-Philadelphia chromosome positive cells. It has been shown that even 
after high dose chemotherapy, patients who are 100% Philadelphia chromosome positive 
exhibit a high percentage of normal cells in their bone marrow and peripheral blood. 
Also, these patients will receive GCSF. These procedures are for peripheral blood 
collection only, not autologous bone marrow collection. The monkey data was generated 
using autologous bone marrow transplant procedures because the technical difficulties 
relating to monkey apheresis have not been resolved to date; therefore, peripheral blood 
collection has not been used in gene marking experiments of animals as extensively as 
bone marrow. 
Dr. Dunbar explained that following recovery from the peripheral blood reimplantation, 
the patients will be treated with 5-FU. Ten days later the patients undergo standard 
bone marrow harvest. Dr. Post asked if 5-FU is a standard part of autologous bone 
marrow transplantation. Dr. Dunbar replied that 5-FU has been used in one study that 
was performed at the University of Virginia on 23 patients with breast cancer or 
lymphoma. Patients who received 5-FU prior to harvest exhibited a more rapid platelet 
recovery than those patients that did not receive this treatment. No adverse treatments 
were observed as a result of the administration of 5-FU. 
Dr. D. Miller asked when the 10 day 5-FU will be administered? Dr. Dunbar responded 
that 5-FU treatment will begin as soon as the patient's blood counts have recovered 
following apheresis. It is important not to wait too long for another treatment because 
the patient might relapse between the different phases of the protocol. 
In the breast cancer protocol, 5-FU treatment has not been included. These patients will 
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