Recombinant DMA Advisory Committee - 
allow all members of the RAC to be able to comment on it. However, he requested that 
the primary and secondary reviewers be given the first copies available so they could 
begin their review in a timely manner. He then adjourned the committee for its lunch 
recess and asked members to return promptly at 1:00 p.m. 
Dr. McGarrity called the committee to order from its lunch recess at 1:10 p.m., and 
called on Dr. Mclvor to present the next agenda item. 
VII. PROPOSED ADDITION TO APPENDIX D OF THE "NIH GUIDELINES" 
REGARDING A HUMAN GENE TRANSFER PROTOCOL ENTITLED 
"AUTOLOGOUS BONE MARROW TRANSPLANT FOR CHILDREN WITH ACUTE 
MYELOGENOUS LEUKEMIA (AML) IN FIRST COMPLETE REMISSION: USE OF 
MARKER GENES TO INVESTIGATE THE BIOLOGY OF MARROW 
RECONSTITUTION AND THE MECHANISM OF RELAPSE": 
Dr. Mclvor said the problem that was being addressed in the protocol was the high rate 
of tumor relapse in the treatment of acute myelogenous leukemia (AML) by autologous 
bone marrow transplant. In the treatment, marrow is first obtained from the leukemic 
patient. Next, the patient undergoes chemotherapy to eliminate tumor cells in the body, 
and then the marrow is reinfused to reconstitute the patient's hematopoietic system. Dr. 
Mclvor said some patients remain disease-free for extended periods following such 
treatment but that the tumor regenerates in a large proportion of cases. The issue was 
whether the chemoradiotherapy was insufficient to eliminate tumor in the patient's body, 
or whether the regeneration of tumor was made possible by cells emanating from the 
reinfused bone marrow. 
Dr. Mclvor said the investigators planned to address this question by exposing the 
marrow to a retroviral vector prior to reinfusion. If integrated retroviral provirus was 
found in the tumor, this would be evidence for an infusion-derived regeneration of 
tumor. If identical integrants were found in both normal and tumorous material post- 
transplant, this would implicate the involvement of stem cells in AML. 
Dr. Mclvor said the disease is very serious and results from such a study would provide 
information which may improve therapy. Further, the overall approach was well thought 
out and in vitro preclinical data were provided to demonstrate that gene transfer into 
human leukemic cells is capable of colony formation. Dr. Mclvor had some questions 
about the protocol, namely: 
1. Assessment of safety risks needed to be looked at since the retroviral 
vector will be introduced into marrow, including stem cells, which would be 
capable of long-term reconstitution in the patient and there is a chance 
that the newly introduced gene sequence could persist in the patients for 
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Recombinant DNA Research, Volume 14 
