Human Gene Therapy Subcommittee - 11/30/90 
REGARDING A HUMAN GENE THERAPY PROTOCOL ENTITLED BMT 9094 - 
RETROVIRAL-MEDIATED GENE TRANSFER OF BONE MARROW CELLS 
DURING AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR ACUTE 
LEUKEMIA: UNDERSTANDING DISEASE RECURRENCE 
Dr. Walters then called on Dr. Gellert to begin the discussion of the next protocol. 
Dr. Gellert said that he would summarize the written review which had been 
supplied to members of the HGTS prior to the meeting. The first concern with the 
protocol was safety. There were two main issues: (1) the introduction of the LNL6 
vector into a heterogeneous population of bone marrow cells whose progeny may 
survive for a long time, and (2) the long life expectancy of those persons who will be 
effectively cured of their leukemia if the bone marrow transplant is successful. 
Dr. Gellert said that the protocol was of no therapeutic benefit to the patients; and 
if any risk existed, it could not be balanced by any benefit to the patient. 
Dr. Gellert said he also had concern as to the results anticipated by the protocol. If 
gene-marked cells are found after reinfusion of the bone marrow in a leukemic 
relapse, it will tell something about the origin of those cells and the bone marrow as 
a source of relapse. However, if no such cells were found, no conclusions could be 
drawn from the experiment as to the source of relapse. Furthermore, with the small 
number of patients to be enrolled, there was a question as to whether any significant 
information could be obtained. 
Dr. Gellert said that the issue of using polymerase chain reaction (PCR) for 
assessment of cell type need to be defined more clearly, and the informed consent 
form needed clarification on who would be expected to pay for possible injuries 
resulting from the experiments. Further issues of insurance coverage needed 
clarification. 
Dr. Parkman addressed the issues of bone marrow transplantation and the sources of 
leukemic cells that cause recurrence. Recurrence could come from residual 
leukemic cells in the body, or from cells which may remain in the bone marrow that 
has been reintroduced into the patient via the transplant. In 60-80% of cases of 
autologous bone marrow transplant, there is a relapse. When transplants are 
accomplished using bone marrow obtained from a histocompatible sibling, 40% of 
patients still relapse. 
Dr. Parkman said that one compounding variable is the issue of graft versus host 
(GVH) disease in allogeneic transplants. In cases of allogeneic transplants when 
people have high amounts of GVH disease, there is a lower relapse rate for 
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Recombinant DNA Research, Volume 14 
