Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
validate the safety and efficacy of the Neuroblastoma Bone Marrow 
Purging System for the removal of neuroblastoma cells from autologous 
bone marrow prior to transplantation. 
Safety End Points: 
(1) The safety of the Neuroblastoma Bone Marrow Purging System for in 
vitro purging of bone marrow will be demonstrated by the sterility and 
viability of the cells for transplant following purging with the proposed 
device. 
(2) The clinical safety of the proposed methods will be assessed by 
demonstrating that the proposed manipulation of the cells for 
transplantation (gene marking and purging) results in: 
(i) no toxic side effects. The vectors to be used in this study for gene 
marking are currently in clinical trials, and in extensive prior 
primate testing have not been associated with any adverse effect. 
A detailed discussion of the safety considerations associated with 
gene marking can be found in Appendix D. 
(ii) no signicant delay to marrow recovery (^500 ANC*//xL). 
Extensive prior studies of immunomagnetic purging for autologous 
bone marrow transplantation have demonstrated the overall safety 
of this approach. In addition, in a group of nine patients who have 
received gene-marked marrow, no delay in hematologic recovery 
has been observed (Malcolm Brenner, personal communication). 
It is reasonable to assume that the time to marrow recovery will, 
at worst, be similar to that of patients treated with autologous, 
purged bone marrow. From calculations based on the POG 
purging study (Graham-Pole et al, 1991), we would therefore 
expect the average time to recovery to be <43 days. Because 
* absolute neutrophil count 
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Recombinant DNA Research, Volume 16 
