Recombinant DNA Advisory Committee - 06/7-8/93 
Dr. Deisseroth stated that patients have received granulocyte colony stimulating factor 
(G-CSF) as part of the Taxol treatment regimen. Therefore, G-CSF will be 
administered to patients receiving transduced ABM cells to allow direct comparison of 
results. Since patients receiving G-CSF still exhibit a certain degree of hematopoietic 
toxicity due to Taxol, any protective effect of MDR-1 expression will be detectable. 
There is a dose window in which Taxol toxicity primarily involves the bone marrow and 
not the neural or gastrointestinal systems; therefore, bone marrow protection can be 
demonstrated. Long-term protection of the bone marrow from Taxol toxicity has been 
demonstrated in the murine model using the same vector proposed for the human study. 
Responding to questions raised by Drs. Post and Smith about the stromal cells used to 
enhance the transduction efficiency of the CD34(+) cells, Dr. Deisseroth stated that the 
monolayer stromal cells are grown from a standard diagnostic bone marrow aspirate 
performed 2 weeks prior to the transduction procedure. In response to Dr. Geiduschek's 
question about the adequacy of RCR safety testing, Dr. Deisseroth stated that many 
safety tests have been performed, but that all of the data has not been prepared for 
presentation at today's meeting. 
Committee Motion 
A motion was made by Dr. Leventhal and seconded by Dr. Dronamraju to approve this 
protocol contingent on submission of the following: (1) data on the pre- and post- 
production RCR testing, and (2) a revised Informed Consent document that incorporates 
the changes suggested by Mr. Capron, Ms. Meyers, Dr. Leventhal and Dr. Walters. The 
motion passed by a vote of 21 in favor, 0 opposed, and no abstentions. 
VII. AMENDMENT TO THE HUMAN GENE THERAPY PROTOCOL ENTITLED: 
TREATMENT OF SEVERE COMBINED IMMUNE DEFICIENCY (SCID) DUE TO 
ADENOSINE DEAMINASE (ADA) DEFICIENCY WITH CD34(+) SELECTED 
AUTOLOGOUS HEMATOPOIETIC STEM CELLS I DR. BLAESE 
Review- Dr. Post 
Dr. Walters called on Dr. Post to present his primary review of the minor modification 
submitted by Drs. R. Michael Blaese and Craig A. Mullen of the NIH, Bethesda, 
Maryland. Dr. Post stated that this modification represents the following significant 
changes to the previously approved protocol: (1) an additional source of cells, i.e., cord 
blood and placenta, (2) an expanded eligibility criterion that includes newborn babies, 
and (3) the administration of transduced CD34( + ) cells alone, and (4) the inclusion of 
additional sites at which the gene therapy procedure will be performed. This 
modification would have been more appropriately handled as an expedited review 
protocol; however, the expedited review procedures were not yet officially incorporated 
into the NIH Guidelines. He recommended approval of this minor modification based 
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