Recombinant DNA Advisory Committee - 09/14-15/92 
Dr. Parkman asked if there are any specific losses that resulted from the double 
depletion process. Dr. Deisseroth explained that the percentage loss of myeloid cells is 
between 20 and 50% during the second selection step. Are the depleted cells early 
progenitor cells being lost or an excess of nonreconstituting cells? The double 
selection/double marking protocol was designed to answer this question. 
Mr. Capron noted that the suggested language offered by Ms. Meyers regarding patient 
autopsy does not appear in the revised informed consent document. Dr. Deisseroth 
agreed that Ms. Meyers' suggested language would appear in the final version of the 
document. 
Dr. Secundy said that the written protocol varies considerably from the protocol that has 
been verbally presented to the RAC. Will a vote for approval endorse the written or 
verbal proposal? The written protocol would be revised to reflect the changes that the 
investigators have presented orally. Dr. Murray stated that such a decision would have 
to be approved by the RAC. Dr. Parkman asked Dr. Deisseroth if the written protocol 
accurately reflects the procedures. Dr. Deisseroth said that the strategies that were 
presented orally accurately reflect the design of the protocol. Dr. Parkman suggested 
that the CD 19 depletion procedure should be incorporated into a revised protocol. Dr. 
D. Miller added that approval of the protocol should be contingent on review and 
approval of the revised protocol by primary reviewers to ensure that questions presented 
have been answered satisfactorily. 
Dr. Krogstad asked what fraction of patient relapses are likely to be interpretable in 
terms of their source. Dr. Deisseroth answered that the number of marked cells in the 
lymphoid population in each category at the time of relapse is approximately 500 cells. 
If the marking frequency is 1%, the probability of the test failing to detect a relapse is 
probably between .004 and 4%. The probability of not detecting a marked relapse is low 
combined with projected number of patients; the probability of all ten patients not 
providing an interpretable answer is extremely low. Dr. D. Miller asked if this 
hypothesis is based on the assumption that all 500 cells will grow. What if the relapse is 
clonal? Dr. Deisseroth stated that relapse is not likely to be clonal. Patients will have 
to be screened and selected to include those with relatively poor prognoses, because this 
patient population yields a higher labelling frequency. 
Committee Motion 
A motion was made by Dr. Parkman and seconded by Dr. Secundy to approve the 
protocol contingent on the following stipulations: (1) submission of a revised outline of 
the cell selection and gene marking procedures for review and approval by Drs. 
Bourquin, Geiduschek, Parkman, and Walters and Ms. Buc; and (2) the informed 
consent document will be revised to reflect minor language modifications. Dr. Murray 
Recombinant DNA Research, Volume 16 
[265] 
