Human Gene Therapy Subcommittee - 11/30/90 
leukemia; however, patients who experience very little GVH disease relapse more 
often. 
Dr. Parkman said in the absence of finding marked bone marrow cells, it would be 
necessary to mark 100% of the leukemic progenitor cells in the bone marrow in 
order to have any statistical likelihood of being able to say that a relapse was caused 
by residual leukemic cells in the patient. Preclinical data on the efficiency of 
progenitor cell marking by the vector is important, and the low number of patients 
being considered for the protocol makes the question of residual disease in the 
patient after chemotherapy a difficult one to answer. 
Dr. Epstein agreed with the comments of Drs. Parkman and Gellert in regard to the 
necessity for more preclinical data on the efficiency of marking by the vector. The 
investigator are responsible for performing such preclinical assessments based on his 
own research, and they should not rely totally on citations from the literature or data 
from other laboratories. The issue of polyclonality or monoclonality of the relapsed 
cells needs clarification. Much of the data and calculations on the probability of 
being able to detect a polyclonal relapse after marking are unclear and require 
further preclinical support. 
Dr. Zallen said that she had a safety concern over whether enough bone marrow 
would be set aside to reinfuse the patient if he/she withdraws from the study 
between the time of having bone marrow drawn and the time of reinfusion. Further, 
there is the problem of the ability of the retroviral vector to insert at various 
locations in the genome and the lack of experience in this area. In the future, 
experience should be presented in terms of "patient months." If this information is 
kept in a registry, there would be the accumulation of vital data to assess long-term 
risks associated with the use of the vector under varying circumstances. 
Dr. Zallen said she was concerned about the conditions under which the informed 
consent would be presented and the ability of the patient to understand the risks. If 
the physician in charge of the bone marrow transplantation is the one discussing the 
risks and benefits of the experiment, the patient may be put in a position of feeling 
he/she has to go along with the procedure to appease the physician. 
Dr. Zallen was concerned that patients were being asked to subsidize the cost of the 
research, and this request was unacceptable. It is important for the protocol to spell 
out more clearly who would be financially responsible if there were problems with 
insurance coverage already in place for these patients. 
Recombinant DNA Research, Volume 14 
[ 377 ] 
