June 1, 1990, Human Gene Therapy Subcommittee Minutes 
necessary to obtain new data on time points in terms of risk and efficacy in order to 
provide the best data possible for an expeditious review. He said he did not believe it 
appropriate for the subcommittee to fail to take such data into account. Dr. Parkman 
said that frequently this had not been the case. He cited examples of data which had 
been previously published, yet not made available by the investigators until the protocol 
was being reviewed at the subcommittee meeting. 
Dr. Leventhal said that she felt a deadline for submission to ORDA two weeks prior to 
the meeting, with ORDA forwarding the material to the members one week prior to the 
date of the meeting, would be proper to allow the subcommittee to digest the material 
prior to the meeting. 
Dr. Walters said he thought this would be an excellent rule of thumb for the future. As 
new information was presented during this course of this discussion, a decision would 
have to be made as to how such data should be classified. He then called on 
Dr. Parkman to present the primary review of the protocol. 
Dr. Parkman said that Dr. Wivel had asked him to present a short historical outline of 
bone marrow transplantation to the subcommittee as a background piece for the review 
of the protocol. Dr. Parkman discussed histocompatibility factors, noting that of six 
different histocompatibility antigens, a child and a parent share only three, the HLA-A, 
B, and D complexes and that often times siblings acquire differing sets of these from the 
parents, therefore, not providing a total HLA match for bone marrow transplantation. 
So, the chances of finding a total HLA-matched donor are greater among siblings than in 
matching the recipient to parent where only three antigens will be the same. He noted 
that the greater the differences in matches in these six HLA antigens between donor and 
recipient, the greater the probability of graft versus host disease in the recipient. 
Dr. Parkman said that graft versus host disease is a function of the T cells. One method 
of dealing with a non-histocompatibly matched donor-recipient pair is to inject marrow, 
having first removed the T cells, and then allowing the stem cells to replace the 
abnormal lymphoid stem cells in the recipient. This solves the problem with T cells. 
Because of B cell problems, these patients are left in an agammaglobulinemic state and 
need lifelong replacement therapy to produce immunoglobulin. 
Dr. Parkman said that the second issue he wished to discuss was natural killer (NK) cell 
activity in relation to predicting who may or may not require drug treatment prior to 
bone marrow transplantation. He said that NK cells are similar to the tumor-infiltrating 
lymphocytes (TILs) being used in human gene therapy protocols. If the patients have 
NK activity and are transplanted with T-cell depleted marrow without cytoreduction, 
there will be engraftment. Without the NK activity, cytoreduction is required for 
successful engraftment. In adenosine deaminase deficiency (ADA), NK activity is greater 
than in severe combined immune deficiency (SCID) and therefore there is an increased 
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