Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
of marked cells is, in itself, a strong indication that relapses are polyclonal. The 
proportion of cells in each marked relapse arising from the purged and unpurged aliquots 
can then be determined using the described methods. Possible outcomes include: 
A. No marked cells detected in any relapses examined. 
B. Marked cells detected. 
i) relapse with all cells containing a marker gene indicating monoclonal 
relapse; detection of this event would be unlikely based on Table 6.2-1 
ii) relapses containing both marked and unmarked cells implying a multiplicity 
of cells capable of inducing relapse; colonies will be grown and analyzed 
a) colonies are positive for both vectors 
b) colonies contain only the vector used in the unpurged marrow 
Outcome A may be explained by (1) relapses are monoclonal and therefore the 
probability of detecting a marked relapse in this number of patients is extremely small, 
(2) bone marrow in clinical remission does not contain cells that contribute to subsequent 
marrow relapse, or (3) the marking procedure does not perform as anticipated (may 
involve multiple issues). In any case, the conclusion would be that the procedure, as 
described here, is not a useful tool for examination of the contribution of transplanted 
marrow to relapse. 
Outcome B implies that patients receiving marrow harvested in clinical remission are 
receiving malignant cells that contribute to relapse, and therefore that purging is, in 
principle, worthwhile. 
Outcome i) is, as indicated above, extremely unlikely to be detected, but 
implies that gene marking would not be a useful tool for evaluating the 
contribution of marrow to relapse, since unrealistically large numbers of 
patients would be required to assess the efficacy of purging. 
Recombinant DNA Research, Volume 16 
[479] 
