Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION. HYLAND DIVISION 
6.3.7. 1 Stopping Rule 
The following table will be used to stop the study for unacceptable toxicity. 
Number of Patients 
Re-evaluate if Number of Successes* is 
Less Than 
7 
4 
8 
5 
9 
6 
* Success is defined as engraftment without use of the back-up marrow and the 
absence of _> Grade 4 toxicities (see Appendix B, Common Toxicity Criteria). 
6. 3. 7. 2 Subsidiary Stopping Rule 
Recent information from the Pediatric Oncology Group study on neuroblastoma purging 
suggests that cell culture may detect tumor colony forming cells in up to half the patients 
in apparent marrow remission at the time of harvest (Graham-Pole, University of Florida, 
Gainesville, personal communication). It is not known whether these cells contribute to 
subsequent relapse. If, however, it becomes clear during the course of the present study 
that in vitro detection of neuroblastoma cells in the marrow concordantly predicts 
subsequent relapse with marked cells, then gene marking for these patients would be 
superfluous. 
We have therefore introduced a subsidiary stopping rule for patients who axe in marrow 
remission by routine analysis but are positive for neuroblastoma by culture or 
immunocytology, and subsequently relapse with marked cells. 
We will test for concordance of the clinical and in vitro results 6 months after 
Recombinant DNA Research, Volume 16 
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