ATTACHMENT D 
EXCERPTS FROM THE JULY 30, 1990, HUMAN GENE THERAPY 
SUBCOMMITTEE - ATTACHMENT D 
PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING 
HUMAN GENE TRANSFER CLINICAL PROTOCOL ENTITLED "USE OF MARKER 
GENES TO INVESTIGATE THE BIOLOGY OF MARROW RECONSTITUTION AND 
RELAPSE OF MALIGNANT DISEASE FOLLOWING AUTOLOGOUS BONE 
MARROW TRANSPLANTATION"; 
Dr. Leventhal said the objectives of the study are to determine: 
1. Whether the source of relapse after autologous bone marrow 
transplantation (ABMT) for marrow derived malignancies is residual 
malignant cells in the harvested marrow or in the patient; 
2. Whether the majority of cases of acute myelogenous leukemia (AML) 
which lack genetic markers represent abnormalities in a multilineage cell; 
and, 
3. What are the mechanisms of autologous reconstitution and the effects of 
stimuli (including growth factors) that modify the process. 
Dr. Leventhal said the protocol will involve patients with glioma, AML and 
neuroblastoma without detectable tumor in the marrow who are eligible for autologous 
bone marrow transplant (ABMT) protocols within St. Jude's Hospital. She said the 
protocol calls for increasing the number of harvested bone marrow cells by 30 percent. 
Thirty percent of the cells will be taken, following cell separation, to be treated and 
transduced with marker genes while the remainder will be frozen. Following reinfusion 
of marrow into the patients, the bone marrow and peripheral blood will be checked for 
appearance of the vector and analyzed in line with the objectives of the study. 
Dr. Leventhal presented the following as questions concerning safety of the protocol: 
1. Is there a reason to think that incubation of bone marrow with viral vector 
will decrease the likelihood of a graft take, and what are the data relevant 
to this point? 
2. Have marrow cells been grown, in vitro, after treatment? 
3. Will the one-third treated and untreated marrows be combined for 
reinfusion? If so, is there a potential for suppression of marrow growth as 
a whole? 
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