Recombinant DNA Advisory Committee - 03/1-2/93 
RECIPIENTS OF MISMATCHED-RELATED OR PHENOTYPICALLY SIMILAR 
UNRELATED DONOR MARROW GRAFTS /DRS. HESLOP, BRENNER, ROONEY 
Review-Dr. Straus 
Dr. Walters called on Dr. Straus to present his primary review of the protocol submitted 
by Drs. Helen E. Heslop, Malcolm K. Brenner, and Cliona Rooney of St. Jude Children's 
Research Hospital, Memphis, Tennessee. 
Dr. Straus stated that the objective of the proposed study is to mark Epstein Barr Virus 
(EBV)-specific cytotoxic T lymphocytes (CTL) with the gene encoding neomycin 
resistance (neo R ). The rationale for this protocol is based on the fact that recipients of 
mismatched related or unrelated bone marrow cells are at a substantial risk for 
developing EBV-associated lymphoproliferative disorders. The investigators propose to 
obtain EBV-specific CTL from the donor, transduce these cells with a retrovirus vector 
encoding neo R , and adoptively transfer the transduced cells to the recipient. The 
recipient will be monitored for reconstitution of the EBV-specific CTL response, which 
would prevent the outgrowth of EBV-transformed T cells and the persistence of marked 
donor cells. The investigators have demonstrated their ability to generate EBV-specific 
CTL with a 5-25% transduction efficiency. 
Intravenous administration of transduced CTL will be initiated day 45 post-bone marrow 
transplantation and continued weekly for a total of 4 weeks. Three groups of patients 
representing 3 to 6 patients per group will receive one of the following dose-escalations: 
(1) 1 x 10 7 to 5 x 10 7 cells, (2) 5 x 10 7 to 1 x 10 8 cells, or (3) 1 x 10 8 to 5 x 10 8 cells. 
Survival of the neo R CTL and the level of EBV-specific DNA from peripheral blood and 
saliva samples will be monitored by PCR amplification. Immunologic responses will be 
monitored in vitro by CTL assays and lymphocyte phenotyping. Dr. Straus stated that the 
investigators have extensive experience with all aspects of the proposed study, and that 
they have addressed the reviewers questions and comments adequately. 
Review-Dr. DeLeon 
Dr. DeLeon noted that the investigators had satisfactorily responded to her comments 
regarding the informed consent document and recommended that the protocol be 
approved. 
Review-Dr. Carmen 
Dr. Carmen stated that this protocol is very well designed. In particular, the 
investigators have provided a discussion about the inappropriateness of using the herpes 
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Recombinant DNA Research, Volume 17 
